Comparing COVID-19 vaccine schedule combinations in adolescents (Com-COV3)
| ISRCTN | ISRCTN12348322 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12348322 |
| EudraCT/CTIS number | 2021-004267-27 |
| IRAS number | 304450 |
| Secondary identifying numbers | IRAS 304450, CPMS 50491 |
- Submission date
- 15/09/2021
- Registration date
- 16/09/2021
- Last edited
- 09/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Since early 2020, COVID-19 has spread around the world. Over 130,000 people in the UK and over 4 million people worldwide have died with COVID-19 (by August 2021). It has made many more people seriously unwell.
Widespread vaccination is helping to save lives, reduce the severity of illness and reduce the spread of the disease. Most adults in the UK have now been vaccinated. By early August 2021, over 88% of adults in the UK had received at least one dose of vaccine.
The vaccination programme in the UK has so far focussed on adults because older adults are more likely to suffer from severe disease or die from COVID-19 than younger people. Although children and young people usually do not become very unwell with COVID-19, some do develop serious illness and a few have died. Young people with COVID-19 occasionally develop a serious inflammatory condition called paediatric multisystem inflammatory syndrome (PIMS-TS). In England, in the first year of the pandemic (until the end of February 2021), 251 under-18-year-olds (about 20 per million) were admitted to intensive care with COVID-19, and 25 (about 2 per million) died; 309 (about 26 per million) developed PIMS-TS.
Vaccinating young people may reduce their risk of severe disease and reduce their chance of missing time in education whilst isolating.
Cohort A of this study will determine the side effect profile, and the immune responses, following schedules using BNT162b2 as a first dose (administered in this study or in the community), and a second dose administered at least 8 weeks later of either BNT162b2 (full or one- third dose) or NVXCoV2373 (full dose). When enrolment to Cohort A of the study commenced, young people aged 12 to 17 years were being invited to receive one dose of the Pfizer-BioNTech vaccine, and many had already been given this. Individuals who had received one dose of the Pfizer-BioNTech vaccine in the community were eligible to enrol in the study at least 8 weeks afterwards.
Following the JCVI recommendation on 29th November 2021 that all 12- to 15-year-olds should be offered a second dose of the BNT162b2 vaccine, the study design was amended to focus on the immune response to BNT162b2. After this date, participants were randomised 1:1 to either full or one-third dose BNT162b2 for their second vaccination. Participants were no longer randomised to the Novavax arm of the study in order to prioritise the arms of the study that were likely to be more policy relevant. This did not reflect any concern regarding the safety or immunogenicity of the Novavax vaccine.
A further review of the study design was undertaken following an interim analysis and on 3rd February 2022, the study Trial Steering Committee advised to stop recruitment for Cohort A. It was also decided to add a new cohort to the study to investigate possible strategies for a third dose of the COVID-19 vaccine in adolescents, following the JCVI's recommendation of a third dose to 16- and 17-year-olds (22nd December 2021).
Cohort B of this study will determine the side effect profile and the immune responses to a third dose of COVID-19 vaccination in adolescents, given at least three months after completion of a two-dose schedule (two full doses of BNT162b2 given at least 8 weeks apart). Participants will be randomised to receive 30μg BNT162b2, 10μg BNT162b2 (given as 0.1ml of adult formulation), 10μg BNT162b2 (given as 0.2ml of paediatric formulation), NVXCov2373 (full dose) or two doses of 4CMenB (Meningococcal Group B vaccine, control group). The control group will be offered Pfizer-BioNTech Comirnaty (Original/Omicron BA.1) 15 µg/15 µg (0.3ml) vaccine 6 months after enrolling in the study.
Who can participate?
Cohort A: This cohort will enrol young people aged 12 to 16 years from various sites in the UK.
Cohort B: This cohort will enrol young people aged 12 to 15.5 years from various sites in the UK.
What does the study involve?
COHORT A
All participants will receive their first immunisation with a standard dose of the Pfizer-BioNTech vaccine. This may either be given in the study, or it may have been given in the community before enrolment in the study.
A second dose of the COVID-19 vaccine will be given at least 8 weeks after the first. The type and dose of vaccine given to each participant will be decided using a process called “randomisation”.
The second dose of vaccine will be one of the following three possibilities:
1. A full standard dose of the Pfizer-BioNTech vaccine
2. A third of a standard dose of the Pfizer-BioNTech vaccine
3. A full standard dose of the Novavax vaccine
Each participant who receives their first vaccine in the study or in the community will have a total of six or five blood tests, respectively, during the course of the study to assess their immune response to the vaccines.
Please note that Participants not randomised by 29th November 2021 will only be randomised to:
1. A full standard dose of the Pfizer-BioNTech vaccine
2. A third of a standard dose of the Pfizer-BioNTech vaccine
COHORT B
The second part of the study (Cohort B) will investigate various options for a third dose booster in adolescents aged 12 to 15.5 years who have already received two doses of BNT162b2 30μg. It will include arms to compare 10μg BNT162b2 administered as either paediatric or adult formulation. For direct comparison, the study will include a blinded control group, receiving a MenB vaccine (which is of similar reactogenicity to COVID-19 vaccines). The rapidly changing situation, with respect to the proportion of the population previously infected and dominant circulating COVID-19 variants, makes it preferable to use randomised rather than historical controls.
What are the possible benefits and risks of participating?
On 15th November 2021 16- and 17-year-olds in the UK were deemed eligible for a second dose of the Pfizer-BioNTech vaccine and on 29th November 2021 this was extended to all adolescents 12 years and over. However, only people aged 16 and older (and participants at increased risk of COVID-19, or household contacts of immunocompromised individuals, based on JCVI and ‘Green Book’ guidelines current on 13th September 2021) are eligible to receive a third dose of a COVID-19 vaccine. Participation in this study will provide 12- to 15-year-olds with the opportunity to receive a third dose of a COVID-19 vaccine, which may boost their immune response to previous doses. The results of this study may be used to guide future decisions about how best to vaccinate young people against COVID-19. By taking part in the study, participants will also have contributed to this.
Where is the study run from?
Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital (UK)
When is the study starting and how long is it expected to run for?
September 2021 to September 2024
Who is funding the study?
1. National Institute for Health Research (NIHR) (UK)
2. UK Vaccine Task Force (VTF) (UK)
3. Novavax (USA)
4. CEPI (Cohort B)
Who is the main contact?
Emma Plested, info@ovg.ox.ac.uk
Contact information
Public
Oxford Vaccine Centre
Centre for Clinical Vaccinology & Tropical Medicine
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865 611400 |
|---|---|
| info@ovg.ox.ac.uk |
Study information
| Study design | Single-blinded randomized controlled phase II multi-centre |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | https://comcovstudy.org.uk/comcov3pis |
| Scientific title | A single-blind, randomised, phase II UK multi-centre study to determine reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules in adolescents |
| Study acronym | Com-COV3 |
| Study hypothesis | Current hypothesis as of 25/05/2022: Cohort A: 1. To evaluate the reactogenicity of heterologous boost at least 8 weeks following BNT162b2 prime vaccine administered to adolescents. 2. To characterise immunogenicity of heterologous and homologous second dose schedules of COVID-19 vaccines Cohort B: 1. To evaluate the reactogenicity of homologous and heterologous boost (third dose) given to adolescents at least 3 months after a two-dose schedule of BNT162b2 2. To determine whether the immune response with BNT162b2 (10 µg, 0.1 ml adult formulation) is non-inferior to that with BNT162b2 (10 µg, 0.2 ml paediatric formulation) 3. To characterise immunogenicity of heterologous and homologous third dose schedules of COVID-19 vaccines when compared with unimmunized controls Cohorts A and B: 1. To assess safety of heterologous second and third dose COVID-19 vaccines 2. Characterisation of frequency of anti-SARS-CoV-2 nucleocapsid IgG seropositivity at enrolment, and subsequent seroconversion through the study 3. To assess reactogenicity and safety of heterologous and homologous second and third dose schedules of COVID-19 vaccines 4. To evaluate immunogenicity, safety and reactogenicity of COVID-19 vaccines in participants sero-positive for SARS-CoV-2 nucleocapsid IgG at enrolment, compared with seronegative _____ Previous hypothesis: 1. To evaluate the reactogenicity of heterologous boost at least 8 weeks following BNT162B2 prime vaccine administered to adolescents. 2. To assess safety of heterologous boost COVID-19 vaccines 3. To characterise immunogenicity of heterologous & homologous boost schedules |
| Ethics approval(s) | Approved 14/09/2021, Berkshire Research Ethics Committee (Easthampstead Baptist Church, South Hill Road, Bracknell, RG12 7NS, UK; +44 (0)207 104 8224; berkshire.rec@hra.nhs.uk), ref: 21/SC/0310 |
| Condition | Prevention of COVID-19 infection in adolescents between 12-16 years of age |
| Intervention | Current interventions as of 24/10/2023: COHORT A: All participants will receive their first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, a dose of 30 µg (0.3 ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of the COVID-19 vaccine, given at least 8 weeks after the first, will be one of the following three possibilities: 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine 3. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) Participants not yet randomised by 29/11/2021 will only be randomised to 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine All vaccines will be administered intramuscularly according to specific SOPs. A computer-generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Participants not yet randomised by 29/11/2021 will be randomised 1:1 using block randomisation (random sizes of 2 and 4). Follow-up is for 10 months. COHORT B: The second part of the study (Cohort B) will investigate various options for a third dose booster in adolescents aged 12 to 15.5 years who have already received two doses of BNT162b2 30 μg. It will include arms to compare 10 μg BNT162b2 administered as either paediatric or adult formulation. For direct comparison, the study will include a blinded control group, receiving a MenB vaccine (which is of similar reactogenicity to COVID-19 vaccines). The rapidly changing situation, with respect to the proportion of the population previously infected and dominant circulating COVID-19 variants, makes it preferable to use randomised rather than historical controls. We aim to recruit 310 participants aged 12 to 15½ years, who have already received two standard doses of the Pfizer vaccine in the community. They will be randomised into five groups, each of which will be given a different vaccine schedule. The options for the third dose of the COVID-19 vaccine we will investigate are: 1. A full dose of the adult Pfizer vaccine 2. A one-third dose of the adult Pfizer vaccine 3. A full dose of the paediatric Pfizer vaccine 4. A full dose of the Novavax vaccine The fifth group in the study will be given their third dose of the COVID-19 vaccine (Pfizer-BioNTech Comirnaty (Original/Omicron BA.1)) later in the study than the other groups. This 'control group' will improve our understanding of the immune responses in the other groups. Following approval of Substantial Amendment 13, the randomisation ratio for Cohort B has been changed from 1:1:1:1:1 to 1:3:3:1:1 to prioritise recruitment to study arms 2 and 3 (i.e., the fractional dose BNT162b2 10µg adult and paediatric formulation groups) to achieve the participant numbers required to meet the study’s co-primary endpoint of non-inferiority between the two BNT162b2 fractional dose groups All vaccines will be administered intramuscularly according to specific SOPs. Follow-up is for 10 months. _____ Previous interventions from 09/06/2023 to 24/10/2023: COHORT A: All participants will receive their first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, a dose of 30 µg (0.3 ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of the COVID-19 vaccine, given at least 8 weeks after the first, will be one of the following three possibilities: 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine 3. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) Participants not yet randomised by 29/11/2021 will only be randomised to 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine All vaccines will be administered intramuscularly according to specific SOPs. A computer-generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Participants not yet randomised by 29/11/2021 will be randomised 1:1 using block randomisation (random sizes of 2 and 4). Follow-up is for 10 months. COHORT B: The second part of the study (Cohort B) will investigate various options for a third dose booster in adolescents aged 12 to 15.5 years who have already received two doses of BNT162b2 30 μg. It will include arms to compare 10 μg BNT162b2 administered as either paediatric or adult formulation. For direct comparison, the study will include a blinded control group, receiving a MenB vaccine (which is of similar reactogenicity to COVID-19 vaccines). The rapidly changing situation, with respect to the proportion of the population previously infected and dominant circulating COVID-19 variants, makes it preferable to use randomised rather than historical controls. We aim to recruit 380 participants aged 12 to 15½ years, who have already received two standard doses of the Pfizer vaccine in the community. They will be randomised into five groups, each of which will be given a different vaccine schedule. The options for the third dose of the COVID-19 vaccine we will investigate are: 1. A full dose of the adult Pfizer vaccine 2. A one-third dose of the adult Pfizer vaccine 3. A full dose of the paediatric Pfizer vaccine 4. A full dose of the Novavax vaccine The fifth group in the study will be given their third dose of the COVID-19 vaccine (Pfizer-BioNTech Comirnaty (Original/Omicron BA.1)) later in the study than the other groups. This 'control group' will improve our understanding of the immune responses in the other groups. Following approval of Substantial Amendment 13, the randomisation ratio for Cohort B has been changed from 1:1:1:1:1 to 1:3:3:1:1 to piroritise recruitment to study arms 2 and 3 (i.e., the fractional dose BNT162b2 10µg adult and paediatric formulation groups) to achieve the participant numbers required to meet the study’s co-primary endpoint of non-inferiority between the two BNT162b2 fractional dose groups All vaccines will be administered intramuscularly according to specific SOPs. Follow-up is for 10 months. _____ Previous intervention as of 24/11/2022: COHORT A: All participants will receive their first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, a dose of 30 µg (0.3 ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of the COVID-19 vaccine, given at least 8 weeks after the first, will be one of the following three possibilities: 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine 3. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) Participants not yet randomised by 29/11/2021 will only be randomised to 1. A full standard dose of the Pfizer-BioNTech vaccine 2. A third of a standard dose of the Pfizer-BioNTech vaccine All vaccines will be administered intramuscularly according to specific SOPs. A computer-generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Participants not yet randomised by 29/11/2021 will be randomised 1:1 using block randomisation (random sizes of 2 and 4). Follow-up is for 10 months. COHORT B: The second part of the study (Cohort B) will investigate various options for a third dose booster in adolescents aged 12 to 15.5 years who have already received two doses of BNT162b2 30 μg. It will include arms to compare 10 μg BNT162b2 administered as either paediatric or adult formulation. For direct comparison, the study will include a blinded control group, receiving a MenB vaccine (which is of similar reactogenicity to COVID-19 vaccines). The rapidly changing situation, with respect to the proportion of the population previously infected and dominant circulating COVID-19 variants, makes it preferable to use randomised rather than historical controls. We aim to recruit 380 participants aged 12 to 15½ years, who have already received two standard doses of the Pfizer vaccine in the community. They will be randomised into five groups, each of which will be given a different vaccine schedule. The options for the third dose of the COVID-19 vaccine we will investigate are: 1. A full dose of the adult Pfizer vaccine 2. A one-third dose of the adult Pfizer vaccine 3. A full dose of the paediatric Pfizer vaccine 4. A full dose of the Novavax vaccine The fifth group in the study will be given their third dose of the COVID-19 vaccine (Pfizer-BioNTech Comirnaty (Original/Omicron BA.1)) later in the study than the other groups. This 'control group' will improve our understanding of the immune responses in the other groups. All vaccines will be administered intramuscularly according to specific SOPs. Follow-up is for 10 months. _____ Previous intervention from 25/05/2022 to 24/11/2022: COHORT A: All participants will receive first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, dose of 30 µg (0.3 ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of COVID-19 vaccine, given at least 8 weeks after the first, will be one of the following three possibilities: 1. A full standard dose of Pfizer-BioNTech vaccine 2. A third of a standard dose of Pfizer-BioNTech vaccine 3. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) Participants not yet randomised by 29/11/2021 will only be randomised to 1. A full standard dose of Pfizer-BioNTech vaccine 2. A third of a standard dose of Pfizer-BioNTech vaccine All vaccines will be administered intramuscularly according to specific SOPs. Computer-generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Participants not yet randomised by 29/11/2021 will be randomised 1:1 using block randomisation (random sizes of 2 and 4). Follow up is for 10 months. COHORT B: The second part of the study (Cohort B) will investigate various options for a third dose booster in adolescents aged 12 to 15.5 years who have already received two doses of BNT162b2 30 μg. It will include arms to compare 10 μg BNT162b2 administered as either paediatric or adult formulation. For direct comparison, the study will include a blinded control group, receiving a MenB vaccine (which is of similar reactogenicity to COVID-19 vaccines). The rapidly changing situation, with respect to proportion of population previously infected and dominant circulating COVID-19 variants, makes it preferable to use randomised rather than historical controls. We aim to recruit 380 participants aged 12 to 15½ years, who have already received two standard doses of Pfizer vaccine in the community. They will be randomised to 5 groups, each of which will be given a different vaccine schedule. The options for the third dose of COVID-19 vaccine we will investigate are: 1. A full dose of adult Pfizer vaccine 2. A one-third dose of adult Pfizer vaccine 3. A full dose of paediatric Pfizer Vaccine 4. A full dose of Novavax vaccine The fifth group in the study will be given their third dose of COVID-19 vaccine later in the study than the other groups. This 'control group' will improve our understanding of the immune responses in the other groups. All vaccines will be administered intramuscularly according to specific SOPs. Follow up is for 10 months. _____ Previous intervention as of 08/12/2021: All participants will receive first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, dose of 30 µg (0.3ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of COVID-19 vaccine, given at least eight weeks after the first, will be one of the following three possibilities: 1. A full standard dose of Pfizer-BioNTech vaccine 2. A third of a standard dose of Pfizer-BioNTech vaccine 3. 4. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) Participants not yet randomised by 29th November 2021 will only be randomised to 1. A full standard dose of Pfizer-BioNTech vaccine 2. A third of a standard dose of Pfizer-BioNTech vaccine All vaccines will be administered intramuscularly according to specific SOPs. Computer generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Participants not yet randomised by 29th November will be randomised 1:1 using block randomisation (random sizes of 2 and 4). Follow up is for 10 months. _____ Previous intervention as of 19/11/2021: All participants will receive first immunisation with a standard dose of 30 µg (0.3ml) of Pfizer-BioNTech (BNT162b2) vaccine. This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of COVID-19 vaccine, given at least eight weeks after the first, will be one of the following four possibilities: 1. A full standard dose of Pfizer-BioNTec vaccine 2. A third of a standard dose of Pfizer-BioNTec vaccine 3. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) All vaccines will be administered intramuscularly according to specific SOPs. Computer generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1 to the three groups using block randomisation (random block sizes of 3 and 6). Follow up is for 10 months. Previous intervention as of 27/10/2021: All participants will receive first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, dose of 30 µg (0.3ml) and 15 µg (0.15ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of COVID-19 vaccine, given at least eight weeks after the first, will be one of the following four possibilities: 1. A full standard dose of Pfizer-BioNTec vaccine 2. A third of a standard dose of Pfizer-BioNTec vaccine 3. A half standard dose of Moderna COVID-19 vaccine, dose of 50 μg (0.25ml) 4. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) All vaccines will be administered intramuscularly according to specific SOPs. Computer generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1:1 to the four groups using block randomisation (random block sizes of 4 and 8). Follow up is for 12 months. Previous intervention: All participants will receive first immunisation with a standard dose of Pfizer-BioNTech (BNT162b2) vaccine, dose of 30 µg (0.3ml) and 15 µg (0.15ml). This may either be given in the study, or it may have been given in the community before enrolment in the study. A second dose of COVID-19 vaccine, given at least eight weeks after the first, will be one of the following four possibilities: 1. A full standard dose of Pfizer-BioNTec vaccine 2. A half standard dose of Pfizer-BioNTec vaccine 3. A half standard dose of Moderna COVID-19 vaccine, dose of 50 μg (0.25ml) 4. A standard dose of Novavax NVXCoV2373, dose of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5ml) All vaccines will be administered intramuscularly according to specific SOPs. Computer generated randomisation list will be prepared by the study statistician. Participants will be randomised 1:1:1:1 to the four groups using block randomisation (random block sizes of 4 and 8). Follow up is for 12 months. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Pfizer BioNTech (BNT162b2), Moderna COVID-19 vaccine, Novavax, NVXCoV2373 |
| Primary outcome measure | Current primary outcome measure as of 25/05/2022: Solicited systemic reactions measured by self-report 7 days after booster immunisation in Cohort A or 7 days after third dose in Cohort B _____ Previous primary outcome measure: Solicited systemic reactions measured by self-report 7 days after booster immunisation |
| Secondary outcome measures | Current secondary outcome measures as of 25/05/2022: 1. Serious adverse events and adverse events of special interest will be collected throughout the study 2. Cellular immune responses by ELISpot on days 0 and 56 post-prime and days 14, 132 and 236 post-boost for Cohort A and days 0, 28, 84, 182, 210 in Cohort B 3. Anti-spike immunoglobulins measured by blood test at days 0 and 56 post-prime and days 132 and 236 post-boost for Cohort A and days 0, 84 and 182 in Cohort B 4. Anti-nucleocapsid immunoglobulins measured by blood test at days 0, 56, 140 and 238 5. Cellular immune responses measured by ELISpot at days 0, 56, 70, 140 and 238 6. Solicited local reactions collected by self-report at 7 days after prime and boost immunisation in Cohort A and 7 days post third dose in Cohort B 7. Unsolicited reactions collected by self-report at 28 days after prime and boost immunisation in Cohort A and 28 days post third dose in Cohort B _____ Previous secondary outcome measures as of 19/11/2021: 1. Serious adverse events and adverse events of special interest will be collected throughout the study 2. Anti-spike immunoglobulins measured by blood test at D0*, 56, 70, 84, 140, 238 3. Anti-nucleocapsid immunoglobulins measured by blood test at D0*, 56**, 140, 238 4. Cellular immune responses measured by ELISpot at D0*, 56, 70, 140, 238 5. Solicited local reactions and unsolicited reactions collected by self-report at 7 days and 28 days, respectively, after prime* and boost immunisation *Only for participants receiving their first dose of COVID-19 vaccine in the study **Only for participants receiving their first dose of COVID-19 vaccine in the community _____ Previous secondary outcome measures: 1. Serious adverse events and adverse events of special interest will be collected throughout the study 2. Anti-spike immunoglobulins measured by blood test at D0*, 56, 70, 84, 182, 364 3. Anti-nucleocapsid immunoglobulins measured by blood test at D0*, 56** 182, 364 4. Cellular immune responses measured by ELISpot at D0*, 56, 70, 182, 364 5. Solicited local reactions and unsolicited reactions collected by self-report at 7 days and 28 days, respectively, after prime* and boost immunisation *Only for participants receiving their first dose of COVID-19 vaccine in the study **Only for participants receiving their first dose of COVID-19 vaccine in the community |
| Overall study start date | 14/09/2021 |
| Overall study end date | 30/09/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 12 Years |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | 148 Cohort A, 310 Cohort B |
| Total final enrolment | 429 |
| Participant inclusion criteria | Current participant inclusion criteria as of 25/05/2022: For Cohort A: 1. Aged 12 to 16 years (inclusive) at enrolment For Cohort B: 1. Aged 12 to 15.5 years (inclusive) at enrolment 2. Already received two doses of 30 μg BNT162b2, the second dose received at least 91 days prior to randomisation For Cohorts A and B: 1. In good health as determined by a trial clinician. Participants may have well-controlled or mild to moderate comorbidity, as long as this would not render them considered as belonging to a 'high-risk' cohort at particular need of additional doses of COVID-19 2. Able and willing (in the Investigator's opinion) to comply with all study requirements 3. Registered with a GP, and willing to allow the investigators to discuss the participant’s medical history with their General Practitioner and access all medical records when relevant to study procedures 4. Parent/legal guardian/participant is willing and able to give written informed consent for participation in the trial. Parent/legal guardian to provide informed consent for participants under the age of 16. Participants aged 16 years will be assumed to be able to provide consent for themselves, however parental support will be encouraged and investigators will reserve the right to refuse enrolment if concerns arise. _____ Previous participant inclusion criteria as of 19/11/2021: 1. Parent/legal guardian/participant is willing and able to give written informed consent for participation in the trial 2. Aged 12 to 16 years inclusive at enrolment 3. In good health as determined by a trial clinician. Participants may have well controlled or mild-moderate comorbidity, as long as this would not render them considered as belonging to a ‘high -risk’ cohort at particular need of 2 doses of COVID-19 vaccine (see exclusion criteria below) as part of the national roll out 4. Able and willing (in the Investigator’s opinion) to comply with all study requirements 5. Registered with a GP, and willing to allow the investigators to discuss the participant’s medical history with their General Practitioner and access all medical records when relevant to study procedures _____ Previous participant inclusion criteria: 1. Parent/legal guardian/participant is willing and able to give written informed consent for participation in the trial 2. Aged 12 to 16 years inclusive at enrolment 3. In good health as determined by a trial clinician. Participants may have well controlled or mild-moderate comorbidity, as long as this would not render them eligible for 2 doses of COVID-19 vaccine (see exclusion criteria below) as part of the national roll out 4. Able and willing (in the Investigator’s opinion) to comply with all study requirements 5. Registered with a GP, and willing to allow the investigators to discuss the participant’s medical history with their General Practitioner and access all medical records when relevant to study procedures |
| Participant exclusion criteria | Current participant exclusion criteria as of 24/11/2022: For Cohort A: 1. Previous receipt of more than one dose of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 For Cohort B: 1. Previous receipt of more than two doses of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 30 µg 2. Previous receipt of the 4CMenB vaccine 3. Participants in Cohort A are not eligible to be enrolled into Cohort B unless they received two full doses of BNT162b2 in Cohort A, and they have completed the Cohort A day 236 study visit. At this point they are eligible to enrol in Cohort B, in which case they will be treated as a new participant and receive a new, unrelated, participant number. For Cohorts A and B: 1. Belonging to a 'high- risk' cohort advised to receive additional doses of a COVID-19 vaccine (participants at increased risk of COVID-19, or household contacts of immunocompromised, based on JCVI and 'Green Book' guidelines current on 28/02/2022). 2. First-degree relative of study team member 3. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days) 4. History of anaphylaxis, allergic disease or reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC/IB-listed ingredients of any study vaccine). This includes latex and polyethylene glycol/macrogol (PEG). 5. Pregnancy, lactation or unwillingness to practice effective contraception from enrolment to 3 months post-study vaccination (for post-menarcheal females only) 6. Malignancy requiring receipt of immunosuppressive chemotherapy or radiotherapy for treatment of solid organ cancer/haematological malignancy within the 6 months prior to consent 7. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 8. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 9. Any serious chronic illness requiring hospital specialist supervision 10. Congenital cardiovascular conditions 11. Severe and/or uncontrolled respiratory disease, gastrointestinal disease, liver disease, renal disease, rheumatological disease, and neurological illness (mild/moderate well-controlled comorbidities are allowed) 12. History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) 13. Significant renal or hepatic impairment 14. Scheduled elective surgery requiring overnight admission and/or general anaesthetic during the trial 15. Insufficient level of English language to undertake all study requirements in the opinion of the Investigators 16. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines 17. Participants who have participated in another research trial involving an investigational product in the past 12 weeks (see exclusion criteria above for enrolment into Cohort B after participation in Cohort A of this study) 18. Note that a prior history of confirmed or suspected COVID-19 is NOT an exclusion criterion for this study, provided the participant otherwise satisfies the health screening criteria for the study _____ Previous participant exclusion criteria from 25/05/2022 to 24/11/2022: For Cohort A: 1. Previous receipt of more than one dose of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 For Cohort B: 1. Previous receipt of more than two doses of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 30 µg 2. Participants who received their second dose of COVID-19 vaccine in Cohort A of this study are not eligible to enrol in Cohort B For Cohorts A and B: 1. Belonging to a 'high- risk' cohort advised to receive additional doses of a COVID-19 vaccine (participants at increased risk of COVID-19, or household contacts of immunocompromised, based on JCVI and 'Green Book' guidelines current on 28/02/2022). 2. First-degree relative of a study site staff member 3. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days) 4. History of anaphylaxis, allergic disease or reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC/IB-listed ingredients of any study vaccine). This includes latex and polyethylene glycol/macrogol (PEG). 5. Pregnancy, lactation or unwillingness to practice effective contraception from enrolment to 3 months post study vaccination (for post-menarcheal females only) 6. Malignancy requiring receipt of immunosuppressive chemotherapy or radiotherapy for treatment of solid organ cancer/haematological malignancy within the 6 months prior to consent 7. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 8. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 9. Any serious chronic illness requiring hospital specialist supervision 10. Congenital cardiovascular conditions 11. Severe and/or uncontrolled respiratory disease, gastrointestinal disease, liver disease, renal disease, rheumatological disease, and neurological illness (mild/moderate well-controlled comorbidities are allowed) 12. History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) 13. Significant renal or hepatic impairment 14. Scheduled elective surgery requiring overnight admission and/or general anaesthetic during the trial 15. Insufficient level of English language to undertake all study requirements in opinion of the Investigators 16. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines 17. Participants who have participated in another research trial involving an investigational product in the past 12 weeks 18. Note that a prior history of confirmed or suspected COVID-19 is NOT an exclusion criterion for this study, provided the participant otherwise satisfies the health screening criteria for the study _____ Current participant exclusion criteria as of 19/11/2021: 1. Previous receipt of more than one dose of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 2. Belonging to a ‘high risk’ cohort advised to receive 2 doses of a COVID-19 vaccine (participants at increased risk of COVID-19, or household contacts of immunocompromised, based on JCVI and ‘Green Book' guidelines current as of 13th September 2021). 3. First degree relative of a study site staff member 4. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days) 5. History of anaphylaxis, allergic disease or reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC/IB-listed ingredients of any study vaccine). This includes latex and polyethylene glycol/macrogol (PEG) 6. Pregnancy, lactation or unwillingness to practice effective contraception from enrolment to 3 months post booster vaccination, for post-menarcheal females only 7. Malignancy requiring receipt of immunosuppressive chemotherapy or radiotherapy for treatment of solid organ cancer/haematological malignancy within the 6 months prior to consent. 8. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 9. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 10. Any serious chronic illness requiring hospital specialist supervision 11. Congenital cardiovascular conditions 12. Severe and/or uncontrolled respiratory disease, gastrointestinal disease, liver disease, renal disease, rheumatological disease, and neurological illness (mild/moderate well controlled comorbidities are allowed) 13. History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) 14. Significant renal or hepatic impairment 15. Scheduled elective surgery requiring overnight admission and/or general anaesthetic during the trial 16. Insufficient level of English language to undertake all study requirements in opinion of the Investigators 17. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines 18. Participants who have participated in another research trial involving an investigational product in the past 12 weeks 19. Note that a prior history of confirmed or suspected COVID-19 is NOT an exclusion criterion for this study, provided the participant otherwise satisfies the health screening criteria for the study Previous participant exclusion criteria: 1. Previous receipt of more than one dose of a COVID-19 vaccine, or a COVID-19 vaccine other than BNT162b2 2. Belonging to a cohort advised to receive 2 doses of a COVID-19 vaccine (participants at increased risk of COVID-19, or household contacts of immunocompromised, based on JCVI and ‘Green Book guidelines). 3. First degree relative of a study site staff member 4. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤14 days) 5. History of anaphylaxis, allergic disease or reactions likely to be exacerbated by any component of study vaccines (e.g. hypersensitivity to the active substance or any of the SmPC/IB-listed ingredients of any study vaccine). This includes latex and polyethylene glycol/macrogol (PEG) 6. Pregnancy, lactation or unwillingness to practice effective contraception from enrolment to 3 months post booster vaccination, for post-menarcheal females only 7. Malignancy requiring receipt of immunosuppressive chemotherapy or radiotherapy for treatment of solid organ cancer/haematological malignancy within the 6 months prior to consent. 8. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 9. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 10. Any serious chronic illness requiring hospital specialist supervision 11. Congenital cardiovascular conditions 12. Severe and/or uncontrolled respiratory disease, gastrointestinal disease, liver disease, renal disease, rheumatological disease, and neurological illness (mild/moderate well controlled comorbidities are allowed) 13. History of active or previous auto-immune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) 14. Significant renal or hepatic impairment 15. Scheduled elective surgery requiring overnight admission and/or general anaesthetic during the trial 16. Insufficient level of English language to undertake all study requirements in opinion of the Investigators 17. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccines 18. Participants who have participated in another research trial involving an investigational product in the past 12 weeks 19. Note that a prior history of confirmed or suspected COVID-19 is NOT an exclusion criterion for this study, provided the participant otherwise satisfies the health screening criteria for the study |
| Recruitment start date | 20/09/2021 |
| Recruitment end date | 30/06/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Oxford
OX3 7LA
United Kingdom
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Heath Park
Cardiff
CF14 4XW
United Kingdom
Nottingham
NG7 2QW
United Kingdom
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0AU
United Kingdom
Manchester
M13 9WL
United Kingdom
Liverpool
L12 2AP
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Broomhall
Sheffield
S10 2TQ
United Kingdom
St. James’s University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Sponsor information
University/education
Clinical Trials Research Governance
Joint Research Office
1st floor, Boundary Brook House
Churchill Drive, Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 289885 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
No information available
No information available
Results and Publications
| Intention to publish date | 30/07/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | Current IPD sharing plan as of 24/10/2023: Individual participant data will be made available when the trial is complete, upon requests directed to the trial’s Chief Investigator Angela Minassian (angela.minassian@bioch.ox.ac.uk) or upon written approval of the sponsor. After approval of a proposal, data can be shared through a secure online platform. All data shared will be anonymised. The type of data available upon request includes datasets generated during and/or analysed during the current study. Previous IPD sharing plan: The datasets generated during and/or analyzed during the current study will be available upon requests directed to Angela Minassian (angela.minassian@bioch.ox.ac.uk) or upon written approval of the sponsor. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 5.1 | 21/12/2021 | 06/01/2022 | No | No |
| Protocol file | version 6.0 | 18/01/2022 | 04/02/2022 | No | No |
| Protocol file | version 7.1 | 09/05/2022 | 25/05/2022 | No | No |
| Protocol file | version 8.0 | 22/09/2022 | 24/11/2022 | No | No |
| Protocol file | version 9.0 | 19/12/2022 | 09/06/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 17/06/2023 | 20/07/2023 | Yes | No | |
| Protocol file | version 10.0 | 31/08/2023 | 24/10/2023 | No | No |
| Protocol file | version 11.0 | 13/12/2023 | 23/02/2024 | No | No |
Additional files
- 40431 Com-COV3 Protocol V5.1 21Dec2021.pdf
- ISRCTN12348322_Protocol_v6.0_18Jan22.pdf
- ISRCTN12348322_Protocol_V7.1_09May2022.pdf
- ISRCTN12348322_PROTOCOL_V8.0_ 22Sep22.pdf
- ISRCTN12348322 Com-COV3 Protocol V9.0 19 Dec 2022.pdf
- ISRCTN12348322_PROTOCOL_V10.0_31Aug23.pdf
- ISRCTN12348322 Com-COV3 Protocol V11.0 13 Dec 2023.pdf
Editorial Notes
09/05/2024: The overall end date was changed from 31/03/2024 to 30/09/2024.
23/02/2024: Uploaded protocol v11.0 (not peer-reviewed) as an additional file.
24/10/2023: The following changes were made to the study record:
1. The interventions were updated.
2. The target number of participants was changed from '148 Cohort A, 380 Cohort B' to '148 Cohort A, 310 Cohort B'.
3. The total final enrolment number was changed from 148 to 429.
4. The recruitment end date was changed from 31/03/2023 to 30/06/2023.
5. Protocol file uploaded.
6. IPD sharing plan added.
20/07/2023: Publication reference and total final enrolment added.
23/06/2023: The intention to publish date was changed from 30/06/2023 to 30/07/2023.
09/06/2023: The following changes were made to the trial record:
1. Uploaded protocol v9.0 (not peer-reviewed) as an additional file.
2. The interventions were changed.
3. The overall end date was changed from 30/09/2023 to 31/03/2024.
23/03/2023: The intention to publish date was changed from 31/03/2024 to 30/06/2023.
19/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 31/03/2023.
2. The overall end date was changed from 31/07/2023 to 30/09/2023.
3. The intention to publish date was changed from 31/12/2023 to 31/03/2024.
4. The plain English summary was updated to reflect these changes.
29/11/2022: The plain English summary was updated.
24/11/2022: The plain English summary, interventions and exclusion criteria were updated. The protocol (not peer reviewed) has been uploaded as an additional file.
05/09/2022: The IPD sharing statement has been added.
23/08/2022: The recruitment end date was changed from 31/08/2022 to 31/12/2022.
25/05/2022: The following changes have been made:
1. The study hypothesis has been changed.
2. The intervention has been changed.
3. The primary outcome measure has been changed.
4. The secondary outcome measures have been changed.
5. The recruitment end date has been changed from 28/02/2022 to 31/08/2022.
6. The overall trial end date has been changed from 31/12/2022 to 31/07/2023
7. The participant inclusion criteria have been changed.
8. The participant exclusion criteria have been changed.
9. The Participant inclusion criteria: Target number of participants has been changed from "270" to "148 Cohort A, 380 Cohort B" and the total target enrolment from 270 to 528.
10. Royal Free NHS Foundation Trust has been added to the trial participating centres.
11. The plain English summary has been updated.
12. An updated protocol has been uploaded.
04/02/2022: The protocol (not peer reviewed) has been uploaded as an additional file.
06/01/2022: The previous protocol file was removed as it was for another trial, and the current protocol was uploaded as an additional file.
22/12/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 05/12/2021 to 28/02/2022.
2. Uploaded protocol (not peer-reviewed) as an additional file.
08/12/2021: The following changes have been made:
1. The plain English summary has been updated.
2. The intervention has been updated.
19/11/2021: The following changes have been made:
1. The intervention has been updated.
2. The secondary outcome measures have been updated.
3. The participant inclusion criteria have been updated.
4. The participant exclusion criteria have been updated.
5. The target number of participants and the total target enrolment number have been changed from 360 to 270.
6. The trial participating centres "Cambridge University Hospitals NHS Foundation Trust", "Manchester University NHS Foundation Trust", "Alder Hey Children’s Hospital NHS Foundation Trust", "Newcastle upon Tyne Hospitals NHS Foundation Trust", "Sheffield Children’s NHS Foundation Trust", and "Leeds Teaching Hospitals NHS Trust" have been added.
7. The plain English summary has been updated.
27/10/2021: The intervention has been updated and the plain English summary has been updated to reflect this change.
25/10/2021: The recruitment end date was changed from 20/10/2021 to 05/12/2021. Cripps Health Centre was added as a trial participating centre.
01/10/2021: The CPMS number was added to the protocol/serial no. field.
21/09/2021: The trial participating centre Noah’s Ark Children’s Hospital for Wales was added.
16/09/2021: Trial's existence confirmed by Berkshire Research Ethics Committee.
