The 6-in-1 Vaccine Study

Plain English Summary

Background and study aims
In 2017 the hepatitis B vaccine was added to the UK routine immunisation programme. An infection with the hepatitis B virus can cause severe inflammation of the liver and can cause severe long-term damage to the liver. To allow the introduction of the Hepatitis B vaccine to the UK’s childhood immunisation schedule without increasing the number of vaccine injections, the previously used ‘5-in-1’ vaccine was replaced by a ‘6-in-1’ vaccine which protects against diphtheria, tetanus, poliovirus, whooping cough (pertussis), hepatitis B and haemophilus influenza B (Hib). There are two licensed ‘6-in-1’ vaccines available and these are called Infanrix-Hexa and Vaxelis. Infanrix-hexa is currently used routinely in the UK. It is known from previous studies that this vaccine works well with the other vaccines in the UK schedule, including the meningococcal B vaccine (MenB, Bexsero), in that it is able to induce a good immune response to all vaccine components and has an acceptable side effect profile. At present this information is not available for the Vaxelis vaccine, and it is important to check this as the components of Vaxelis are slightly different from Infanrix hexa. If it can be shown that immunisation with Vaxelis creates a similar response from the immune system to Infanrix hexa and is just as safe when given in the immunisation schedule along with the MenB vaccine, the NHS will be able to use either vaccine for children in the UK. Having the option to use either of the 6 in 1 vaccines is important to ensure all children continue to be protected even if one vaccine becomes temporarily unavailable. To do this the researchers will enrol 240 infants, 8 to 13 weeks of age, and randomly allocate them to receive either 6 in 1 Infanrix-hexa or Vaxelis along with the routine infant UK immunisation schedule. Blood tests will be taken at 5 and 13 months of age to check the immune responses to these vaccines.

Who can participate?
Infants aged 8-13 weeks who are due to receive their primary immunisations can be enrolled in this study if their parent(s)/legal guardian(s) are over 16 years of age and willing to consent to enrol their child in the study and comply with the study protocol. These infants must live in the Thames Valley where the study is being conducted and have been born ≥ 37 weeks gestational age. Infants with confirmed immunodeficiency, previous anaphylaxis (allergic reaction) to any constituent or excipient in one of the vaccines, a latex allergy or another significant disease which might put the participant at risk will not be eligible to participate in the study.

What does the study involve?
The study involves six visits over approximately 11 months. All study visits are conducted at the participant's home or at a convenient location. Four of the visits (at 2, 3, 4 and 12 months) involve administering the routine infant immunisations and either Infanrix-hexa or Vaxelis depending on which group the infant is randomly allocated to. Two of the visits (at 5 and 13 months) involve a blood test. Participants are provided with numbing cream to apply to the skin before this procedure to minimise any pain or discomfort. After the vaccine visits parents/legal guardians are asked to complete a 5-day symptom diary.

What are the possible benefits and risks of participating?
The benefits include participants receiving their routine vaccinations in their own home up until 12 months of age. These visits are conducted by trained nurses and doctors and are arranged at a convenient time for the families. The researchers will also test the immune response to the vaccines received, and if any child were to have an inadequate immune response to the Hib component of the 6-in-1 vaccines they arrange for a booster dose of the appropriate vaccine. This information would not otherwise be available. All vaccines (as with any medicine) can sometimes cause side effects. The most common side effects include crying, lethargy, fever, reduced appetite, vomiting and redness/swelling and pain at the site of the injection. Very rarely (less than 1 in 1 million cases) a vaccination can cause a severe allergic reaction (anaphylaxis), which typically occurs soon after vaccine administration. The study team will ensure all participants are observed for 15 minutes after vaccination and are trained and have equipment to treat this should it occur. The blood tests can sometimes cause temporary bruising or tenderness. Discomfort at the time of sampling will be reduced by using anaesthetic cream to numb the skin.

Where is the study run from?
The study is being coordinated and carried out by the Oxford Vaccine Group (UK)

When is the study starting and how long is it expected to run for?
Recruitment to the study will start from March 2019 and continue until October 2019. The trial end date is September 2021.

Who is funding the study?
Funding has been received from MCM, the vaccine manufacturer of Vaxelis

Who is the main contact?
Parvinder Aley
parvinder.aley@paediatrics.ox.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

University of Oxford
University/education

University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom

"ROR"	https://ror.org/052gg0110

Funders

Funder type

Industry

Results and Publications

Study outputs

Additional files

36421 Protocol V4.0 17AUG20.pdf

6in1 Study SAP V2.0 02July21.pdf

Editorial Notes

06/01/2023: IPD sharing statement added.
05/01/2023: Publication reference added.
17/10/2022: The following changes were made to the trial record:
1. The intention to publish date was changed from 30/09/2022 to 31/01/2023.
2. The total final enrolment was added.
06/10/2022: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The statistical analysis plan was uploaded as an additional file.
04/08/2020: The recruitment end date was changed from 31/07/2020 to 21/04/2020.
13/11/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 25/03/2019 to 01/07/2019.
2. The recruitment end date was changed from 31/10/2019 to 31/07/2020
22/03/2019: The condition has been changed from “Specialty: Children, Primary sub-specialty: Allergy, Infection and Immunity” to “Vaccination against diphtheria, tetanus, pertussis, polio, haemophilus influenza B (Hib) and hepatitis B virus (HBV)” following a request from the NIHR.
12/03/2019: Trial's existence confirmed by the NIHR.