A study of three malaria vaccines to prevent the transmission of malaria in adults in Mali: TBVax2
| ISRCTN | ISRCTN13649456 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13649456 |
- Submission date
- 19/06/2022
- Registration date
- 28/06/2022
- Last edited
- 13/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Malaria is a disease that affects many people in Africa, including Mali. Malaria is caused by small germs that are carried between people by certain mosquitoes. When a person is bitten by an infected mosquito, they may develop malaria. While some people who are infected do not show any symptoms, others may become very sick or even die.
The goal of this study is to develop a vaccine that will safely reduce the spread of malaria in the community by preventing mosquitos from carrying the malaria germs from person to person. The kind of vaccine being developed could decrease the number of malaria germs in the entire community, and could later be combined with a vaccine that prevents people from getting infected.
The combination vaccine being tested in this study contains a protein (Pfs230) that is found on the surface of the malaria germ, a recombinant Pfs48/45 6C domain fused with glutamate-rich protein (R0.6C) and the individual vaccine ProC6C is a recombinant Pfs48/45 6C domain fused with Pfs230-Pro domain using a Circumsporozoite protein linked. The other vaccine parts, EPA, Alhydrogel, and Matrix-M are products that are added to the vaccine to improve the body’s immune response to that protein. The immune response is what the body uses to fight germs. The Pfs230 protein has been previously tested combined with other agents in Mali. The R0.6C and ProC6C have also been previously tested, and have been shown to be safe and induced good immune responses. This is the first time these two vaccine parts (R0.6C and Pfs230) have been combined together into one vaccine and the first tests in humans. The study will start with a low dose of the experimental malaria vaccine. If there are no safety concerns after testing this dose, we study will continue with higher doses.
This study aims to learn if the experimental malaria vaccine is safe and what side effects it may cause in Malian adults. The study also aims to see if people who get the vaccine develop similar immune responses that have been seen with other vaccines that reduce the spread of malaria in the community. Volunteers with be given 3 injections of a study vaccine and be followed during the malaria transmission season. The volunteers will receive physical exams and blood samples will be collected to study how the immune system reacts to the vaccine. The results of research tests from volunteers who received the experimental malaria vaccine will be compared to the results from volunteers who received the approved rabies vaccine to look for differences.
Who can participate?
Healthy adult volunteers resident in Doneguebougou, Mali, or surrounding villages
What does the study involve?
The study will comprise about 23 study visits over about 14 to 16 months. At 3 of these visits, the volunteers will receive an injection of either the experimental malaria vaccine or a comparator vaccine. The comparator vaccine is a rabies vaccine (Verorab Rabies Vaccine or a similar rabies vaccine). The Verorab Rabies Vaccine is approved in Mali. Volunteers will receive only one of these vaccines in this study, not both, and will not know which vaccine they receive. Both the experimental malaria vaccine and the comparator rabies vaccine will be called the “study vaccines.”
Blood will be collected from a vein in the volunteer's arm using a needle or by fingerstick at most visits. The blood samples will be used for clinical and research tests. Females who can get pregnant will have pregnancy testing during this study. Because the experimental malaria vaccine can have risks during pregnancy, you cannot be in this study if you are pregnant or planning to become pregnant.
What are the possible benefits and risks of participating?
Participants will not receive direct benefits from this study. We hope that what we learn in this study will help us make an effective new malaria vaccine that will help prevent the spread of malaria.
Participants are at risk of experiencing:
1. Study vaccines: You may experience side effects or symptoms from the study vaccines. The most common side effects seen in people who received these vaccines or parts of the vaccines are the following:
1.1. Side effects near the injection site: pain, swelling, redness, or small lumps under the skin near the injection site
1.2. General side effects throughout the body:
1.2.1. Fever
1.2.2. Headache
1.2.3. Muscle or joint pain
1.2.4. Feeling tired or ill
1.2.5. Nausea
1.2.6. Vomiting
1.2.7. Diarrhea
1.2.8. Swelling of lymph nodes
Side effects from a study on vaccines are generally mild and usually get better without treatment. While most symptoms are mild, it is possible that you could develop serious side effects from the vaccine or other side effects that we do not know about. We will monitor you closely for all side effects and give you treatment if needed.
2. Blood draws: Side effects from blood draws may include pain, bruising, bleeding, infection or feeling lightheaded.
Where is the study run from?
University of Sciences, Techniques and Technologies of Bamako (Mali)
When is the study starting and how long is it expected to run for?
February 2022 to February 2024
Who is funding the study?
European and Developing Countries Clinical Trials Partnership (Netherlands)
Who is the main contact?
Prof Issaka Sagara
isagara@icermali.org
Contact information
Public
Faculty of Medicine and Odonto-Stomatology & Faculty of Pharmacy
University of Sciences, Techniques and Technologies of Bamako (USTTB)
PO Box 1805 Point G
Bamako
BP 1805
Mali
 ORCID ID |
0000-0002-8555-9983 |
|---|---|
| Phone | +22 376459079 |
| isagara@icermali.org |
Principal Investigator
Faculty of Medicine and Odonto-Stomatology & Faculty of Pharmacy
University of Sciences, Techniques and Technologies of Bamako (USTTB)
PO Box 1805 Point G
Bamako
BP 1805
Mali
| Phone | +22 376253304 |
|---|---|
| katile@icermali.org |
Scientific
LMIV/NIAID/NIH
29 Lincoln Drive
Building 29B, Room 4NN06
Bethesda
MD 20892
United States of America
| Phone | +1 301 761-5089 |
|---|---|
| patrick.duffy@nih.gov |
Scientific
Serum Statens Institute (SSI)
Copenhagen
2300
Denmark
| Phone | +45 32 68 32 68 |
|---|---|
| mth@ssi.dk |
Study information
| Study design | Phase I dose-escalating randomized comparator-controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Prevention |
| Participant information sheet | 41949 English_Consent_TBVax2_Version 2.0_14042022 - Clean.pdf |
| Scientific title | Phase I, dose-escalating, randomized, comparator-controlled trial of the safety, tolerability, and immunogenicity of the co-administration of transmission-blocking vaccines (R0.6C-AlOH/ Matrix-M™ with Pfs230D1 EPA/Matrix-M™) and individual comparators (R0.6C-AlOH/ Matrix-M™; ProC6C-AlOH/ Matrix-M™ and Pfs230D1 EPA/Matrix-M™) against Plasmodium falciparum in adults in Mali: TBVax2 |
| Study acronym | TBVax2 |
| Study hypothesis | Malaria is transmitted by Anopheles mosquitoes. During a blood meal from an infected person, the female mosquito ingests parasites, including gametocytes, the sexual forms of the parasite. Inside the mosquito midgut, male and female gametes fertilize to form a zygote, which further develops into an elongated ookinete form. The ookinete migrates to the outer surface of the midgut and develops into an oocyst, which undergoes multiple rounds of nuclear division to produce thousands of sporozoites that then migrate to the salivary glands. When the mosquito takes another blood meal, it injects sporozoites with its saliva, transmitting the malaria parasite to another person. This is a Phase 1, dose-escalating, randomized, comparator-controlled study to assess the safety, tolerability, immunogenicity, and transmission-blocking activity (TBA) of a 3 dose regimen of Study Agents (four total) versus rabies vaccine in healthy adults. This will be a first-in-human assessment of the co-administration of R0.6C-AlOH/Matrix-M with Pfs230D1-EPA/Matrix-M. |
| Ethics approval(s) | Approved 19/04/2022, University of Sciences, Techniques and Technologies of Bamako (USTTB) Ethics Committee (FMOS-FAPH/USTTB, BP 1805 Point G, Bamako, Mali; +223-2022-5277; mdiakite@icermali.org), ref: 2022/84/CE/USTTB |
| Condition | Prevention of Plasmodium falciparum transmission in humans |
| Intervention | This is a study to assess the safety, tolerability, immunogenicity, and transmission-blocking activity (TBA) of a three-dose regimen of Study Agents (four total) versus rabies vaccine in healthy adults. This will be a first-in-human assessment of the co-administration of R0.6C-AlOH/Matrix-M with Pfs230D1-EPA/Matrix-M. Participants will be randomized to one of the study arms. Participants will be followed for 12 months from the last dose of the study vaccine for safety and tolerability, as well as immunogenicity and functional antibody responses. 1. Group 1: Pilot Group 1.1. Arm 1a (n=5): 30 µg ProC6C-AlOH/15 µg Matrix-M (this arm is to be enrolled only if safety has not already been demonstrated in the ongoing first-in-human trial PACTR202201848463189) 1.2. Arm 1b (n=5): 30 µg R0.6C-AlOH/15 µg Matrix-M co-administered with 12.5 µg Pfs230D1-EPA/25 µg Matrix-M 1.3. Arm 1c (n=5): rabies vaccine (standard dose) 2. Group 2: Main Group 2.1. Arm 2a (n=20): 100 µg R0.6C-AlOH/50 µg Matrix-M and normal saline 2.2. Arm 2b (n=20): 100 µg ProC6C-AlOH/50 µg Matrix-M and normal saline 2.3. Arm 2c (n=20): 40 µg Pfs230D1-EPA/50 µg Matrix-M and normal saline (Pfs230D1-EPA regimen may be adjusted based on results of ongoing clinical trial NCT05135273) 2.4. Arm 2d (n=20): 100 µg R0.6C-AlOH/25 µg Matrix-M co-administered with 40 µg Pfs230D1-EPA/25 µg Matrix-M (Pfs230D1-EPA regimen may be adjusted based on ongoing clinical trial PACTR202201848463189) 2.5. Arm 2e (n=20): rabies vaccine (standard dose) Added 13/02/2024: Arm 3 (n=5): 40 µg Pfs230D1-EPA/50 µg Matrix-M given at 0, 1, and 6 months. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | R0.6C-AlOH/Matrix-M™, ProC6C/Matrix-M™, Pfs230D1-EPA/Matrix-M™, R0.6C-AlOH/Matrix-M™ Co-administered with Pfs230D1-EPA/Matrix-M™, Verorab Rabies Vaccine |
| Primary outcome measure | 1. Incidence of serious adverse events (SAEs) possibly, probably or definitely related to co-administered vaccinations, measured clinically and by laboratory assessments, measured 7 days after each vaccination in the period from first vaccinations up to 1 month after the last immunization: 1.1. That results in death 1.2. That is life-threatening (places the participant at immediate risk of death from the event as it occurred) 1.3. That requires inpatient hospitalization or prolongs an existing hospitalization 2. Incidence of solicited grade 3 local and systemic adverse events (AEs) possibly, probably or definitely related to co-administered vaccinations, measured clinically and by laboratory assessments, measured 7 days after each vaccination in the period from first vaccinations up to 1 month after the last immunization: 2.1. Systemic adverse events: 2.1.1. Fever (temperature ≥ 38.0°c) 2.1.3. Headache 2.1.4. Nausea/vomiting 2.1.5. Diarrhea 2.1.6. Abdominal pain 2.1.7. Fatigue 2.1.8. Malaise 2.1.9. Myalgia 2.1.10. Arthralgia 2.1.11. Urticarial 2.2. Local reactogenicity following the injection: 2.2.1 Pain/tenderness 2.2.2. Erythema/redness 2.2.3. Swelling 2.2.3. Induration 2.2.4. Pruritus 2.2.5. Limitation of arm movement |
| Secondary outcome measures | 1. The functional transmission reducing activity (TRA) measured using the standard membrane feeding assay of volunteer sera at two weeks after the third immunizations, compared to baseline within each of the Study Agent Groups 2. The TRA measured using the standard membrane feeding assay of volunteer sera at other time points (2 weeks after first and second immunizations and 4 months post third vaccination) compared to baseline (D0) in each of the Study Agent Groups 3. The Study Agent antibody quantity in volunteer sera measured by ELISA two weeks after each dose and at 4 months post dose compared to baseline (D0) in each of the three dose-adjuvant combinations 4. Incidence of adverse events possibly, probably or definitely related to any investigational vaccines measured clinically and by laboratory assessments at study duration period |
| Overall study start date | 02/02/2022 |
| Overall study end date | 19/02/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | 110 |
| Total final enrolment | 115 |
| Participant inclusion criteria | 1. Aged between 18 years old and <50 years old 2. Available for the duration of the trial 3. Known resident or long-term resident (more than 1 year) of Doneguebougou or surrounding villages 4. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process 5. In good general health and without clinically significant medical history in the opinion of the investigator 6. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to Study Day 0 and until 1 month after the last vaccination 7. Willing to have blood samples stored for future research |
| Participant exclusion criteria | 1. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (β hCG) test (if female). Note: Pregnancy is also a criterion for discontinuation of any further vaccine dosing. 2. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject’s age. 3. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels outside the local laboratory-defined limits of normal. Subjects may be included at the investigator’s discretion for “not clinically significant” values outside of normal range and ≤ Grade 2. 4. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. Subjects may be included at the investigator’s discretion for “not clinically significant” values outside of the normal range and ≤ Grade 2. 5. Infected with HIV 6. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies 7. History of receiving any investigational product within the past 30 days 8. Current or planned participation in an investigational vaccine study until the time period of the last required study visit under this protocol 9. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months 10. History of a severe allergic reaction or anaphylaxis 11. Known: 11.1. Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years 11.2. Autoimmune or antibody-mediated disease including but not limited to: 11.2.1. Systemic lupus erythematosus 11.2.2. Rheumatoid arthritis 11.2.3. Multiple sclerosis 11.2.4. Sjögren’s syndrome or autoimmune thrombocytopenia 11.3. Immunodeficiency syndrome 11.4. Seizure disorder (exception: history of simple febrile seizures) 11.5. Asplenia or functional asplenia 11.6. Use of chronic (≥14 days) oral or intravenous (IV) corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0 11.7. Allergy to latex or neomycin 12. Receipt of: 12.1. Live vaccine within 4 weeks prior to enrollment or a killed vaccine within 2 weeks prior to enrollment 12.2. Immunoglobulins and/or blood products within the past 6 months 12.3. Investigational malaria vaccine in the last 2 years 13. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives or would render the subject unable to comply with the protocol |
| Recruitment start date | 30/06/2022 |
| Recruitment end date | 31/08/2022 |
Locations
Countries of recruitment
- Mali
Study participating centre
University of Sciences, Techniques and Technologies of Bamako (USTTB)
PO Box 1805 Point G
Bamako
BP 1805
Mali
Sponsor information
University/education
Faculty of Medicine and Odonto-Stomatology & Faculty of Pharmacy
PO Box 1805 Point G
Bamako
BP 1805
Mali
| Phone | +22 376459079 |
|---|---|
| isagara@icermali.org | |
| Website | https://pftv.org |
"ROR" |
https://ror.org/023rbaw78 |
Funders
Funder type
Research organisation
Private sector organisation / International organizations
- Alternative name(s)
- Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
- Location
- Netherlands
Results and Publications
| Intention to publish date | 19/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from (Issaka Sagara, isagara@icermali.org). The type of data which will be made available include the demographic data (age, gender) adverse events data (clinical and laboratory parameters), the immunology (antibody to the different transmission-blocking vaccine candidates), the vaccine arm and the Study ID. Those data will be available at the latest one year after the last vaccination and can be kept at the different repositories as lasting as required by the specific regulatory requirement. Data will be protected from unauthorized person usage. The data will be shared with different stakeholders, including EDCTP, the ethics committee, the DSMB (Data Safety and Monitoring Board) and the regulatory health authorities. The data will be analysed according to predefined data analysis plan. The consent form already states that data will be published or shared with the above-indicated stakeholders but the personal identification code (PIC) will not be revealed. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 24/06/2022 | No | Yes | |
| Protocol file | version 3.0 | 15/06/2022 | 08/08/2022 | No | No |
| Other files | Interim safety report | 15/06/2023 | 11/01/2024 | No | No |
Additional files
- 41949 English_Consent_TBVax2_Version 2.0_14042022 - Clean.pdf
- Participant information sheet
- ISRCTN13649456_PROTOCOL_V3.0_15Jun22.pdf
- ISRCTN13649456 TBVax2_Mali_PfTBV_SafetyReport#3_15June2023AK_MT.pdf
- Interim safety report
Editorial Notes
13/02/2024: The following changes were made to the study record:
1. The interventions were updated.
2. Total final enrolment added.
3. The overall study end date was updated from 31/01/2023 to 19/02/2024.
4. The intention to publish date was changed from 31/01/2024 to 19/02/2025.
11/01/2024: A report was uploaded as an additional file.
08/08/2022: The following changes were made to the trial record:
1. Uploaded protocol (not peer reviewed).
2. The recruitment end date was changed from 24/08/2022 to 31/08/2022.
3. The target number of participants was changed from 115 to 110.
