Booster Dose of SARS-CoV-2 Vaccine with Adjuvant [COVID-19]
Research type
Research Study
Full title
Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccines with AS03 Adjuvant in Adults 18 Years of Age and Older as a Primary Series and Immunogenicity and Safety of a Booster Dose of SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (two Monovalent and one Bivalent)
IRAS ID
302236
Contact name
Adam Finn
Contact email
Sponsor organisation
Sanofi Pasteur Inc.
Eudract number
2020-003370-41
Duration of Study in the UK
1 years, 3 months, 3 days
Research summary
COVID-19 is a contagious disease that has quickly infected many people all over the world and continues to be a major public health concern. There are currently several vaccines that have been shown to protect against COVID-19 that have been approved/authorised and are being given to people in many countries. However, further vaccines must be developed to meet global demand and emerging virus variants [i.e. type of coronavirus]. This study investigates a new COVID-19 vaccine called SARS-CoV-2 AS03 Adjuvanted Recombinant Protein Vaccine. It consists of a virus “spike” protein used in other authorised COVID-19 vaccines and an adjuvant, AS03. Adjuvants are ingredients added to help a vaccine work better by increasing the immune response. This COVID-19 study vaccine is either monovalent (contains the spike protein antigen from 1 variant) or bivalent (contains the spike protein antigen from 2 variants). The trial has been set-up to determine which vaccine dose provides the desired safety profile and immune response. Additionally, the study will determine if the vaccines are safe and can stimulate similar immune responses between the different variants that cause COVID-19 after 2 primary injections or 1 booster injection, and if a booster injection can increase and broaden the immune response against these variants. A total of 5412 participants, 18 years of age and older are planned to take part in the study in United States, Honduras, and other parts of the world. In the UK, participants will receive a single booster vaccine. Blood samples and nasal swabs will be collected from each participant and blood sample for cellular mediated immunity and saliva samples from randomly selected participants. Participants will be involved in the study for 12 months.
Lay summary of study results: Key information about this study• What is CoV2 preS dTM-AS03? This is a protein-based vaccine that was developed to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19 disease. The CoV2 preS dTM-AS03 study vaccine contains SARS-CoV-2 strains called “antigens”. When injected in the body, these antigens trigger what is called an “immune response”. The immune response causes the body to make germ-fighting chemicals called “antibodies”. The antibodies can attack the SARS-CoV-2 virus. The CoV2 preS dTMAS03 study vaccine was approved in Europe and the United Kingdom as a COVID-19 Booster vaccine in adults who are 18 years of age and older who have previously received other types of COVID-19 vaccines (a messenger ribonucleic acid [mRNA] or adenovirus-vector COVID-19 vaccine).
• Reason for this study: The purpose of this study was to evaluate whether the CoV2 preS dTM-AS03 study vaccine was safe and induced antibodies.
• What was tested: Different formulations of the CoV2 preS dTMAS03 study vaccine with different antigens and different antigen/adjuvant quantities were tested.
• Who took part in this study:o In Part 1, 721 people who had not been previously vaccinated with a COVID-19 vaccine took part in the study in 2 countries o In Part 2, 2,602 people who had been vaccinated with a COVID19 vaccine took part in the study in 6 countries.
• Results of the study: All CoV2 preS dTM-AS03 study vaccine formulations tested induced antibodies in people.
• Safety: All CoV2 preS dTM-AS03 study vaccine formulations tested were safe and well-tolerated.
Full study name: Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccines with AS03 Adjuvant in Adults 18 Years of Age and Older as a Primary Series and Immunogenicity and Safety of a Booster Dose of SARSCoV-2 Adjuvanted Recombinant Protein Vaccines (two Monovalent and one Bivalent)1 General information about the study
Why the study was done
The CoV2 preS dTM-AS03 study vaccine was developed in response to the COVID-19 pandemic.
What is COVID-19 disease?
COVID-19 is a contagious disease that has quickly infected many people all over the world. The symptoms usually include fever, cough, and shortness of breath, among others. The symptoms can last from several days to 2 or more weeks. Older adults and people with long-term health problems, especially of the lungs and heart, are at higher risk of having complications than young healthy children and adults. COVID-19 may sometimes cause severe problems such as pneumonia (a lung infection) and serious trouble breathing, which can lead to a hospital stay and can cause death.
What did researchers want to find out?
This was a Phase 2/3 study with 2 parts. Researchers wanted to evaluate if vaccination with each formulation of the CoV2 preS dTM-AS03 study vaccine was safe and induced antibodies in people who had not received a COVID-19 vaccine before the study (Part 1) and in people who had received a COVID-19 vaccine before the study (Part 2).
Where and when the study took place
• Part 1 started in February 2021, ended in May 2022, and took place in 2 countries (Honduras and the United States).
• Part 2 started in July 2021, ended in February 2023, and took place in 6 countries (Australia, France, Honduras, Spain, the United Kingdom, and the United States).2 Who took part in the study?
Who could take part in the study
• Part 1: adults who were 18 years of age and older and had not been vaccinated with a COVID-19 vaccine before starting the study • Part 2: adults who were 18 years of age and older who had been vaccinated with a COVID-19 vaccine 4 to 10 months before starting the studyWho could not to take part in the study
People with any medical problems or medical history - or anything else that made them unsuitable for the study.
About the people who took part in the study In Part 1, 721 people in total took part, including 362 men and 359 women, who were 18 years of age or older. They were from Honduras (140 people) and the United States (582 people).
In Part 2, 2,602 people in total took part, including 1,262 men and 1,340 women, who were 18 years of age or older. They were from Australia (363 people), France (375 people), Honduras (80 people), Spain (83 people), the United Kingdom (307 people), and the United States (1,409 people).3 What vaccine was studied?
About the study vaccine CoV2 preS dTM-AS03 The CoV2 preS dTM-AS03 study vaccine contains an “antigen” and an “adjuvant”. Antigens can trigger the body’s immune system to produce antibodies that fight disease. Antibodies are proteins in the blood which are part of your immune system. The antigen in the study vaccine is the spike protein that has been copied from the SARS-CoV-2 virus. Adjuvants are ingredients added to help a vaccine work better by increasing the immune response. The adjuvant in this study is called AS03.
How was it decided which group people were in?
In Part 1, participants were randomly assigned to be in 1 of 3 different groups, with each group receiving a different formulation of the CoV2 preS dTM-AS03 study vaccine. Participants were assigned to their group by chance, like flipping a coin, and they did not know which study vaccine formulation they received until the study was over.
Part 2 had 2 main groups called “Booster Cohort 1” and “Booster Cohort 2”. All participants in Booster Cohort 1 were given the same formulation of the CoV2 preS dTM-AS03 study booster vaccine. In Booster Cohort 2, participants were randomly assigned to be in 1 of 2 different groups, with each group receiving a different formulation of the CoV2 preS dTM-AS03 study booster vaccine. Participants were assigned to their group by chance, like flipping a coin, and they did not know which study vaccine formulation they received until the study was over.How was the vaccine given?
The CoV2 preS dTM-AS03 study vaccine was injected in the upper arm muscle as a 2-dose primary series given 21 days apart (Part 1) or as a single dose of one of the formulations (Part 2). This study was “modified double-blind”. This means that neither the participant taking part, nor the study doctors knew who was given which vaccine, but the person who injected the vaccine did. This was done to make sure that the study results were not influenced in any way. In Part 2, Booster Cohort 1, an “open-label” design was also included where people knew which formulation they received.Doses tested
Different formulations of the CoV2 preS dTM-AS03 study vaccine were tested. Vaccines are called “monovalent” if they contain 1 antigen or “bivalent” if they contain 2 antigens. Part 1 tested one monovalent (MV) vaccine with 3 different antigen quantities. Part 2 tested 2 monovalent vaccines with different antigens (MV [D614] or MV [B.1.351]) and a bivalent (BV) vaccine (BV [D614+B.1.351]). In addition, Part 2 included exploration of one of the monovalent vaccines tested at different antigen and adjuvant quantities, and with or without adjuvant.4 Results of the study
Part 1 showed that the CoV2 preS dTM-AS03 study vaccine induced antibodies in people who had not already been vaccinated with COVID-19 vaccine. The level of antibodies increased when the quantity of antigen also increased. Part 2 showed that all formulations of the CoV2 preS dTM-AS03 study vaccine induced antibodies in people who had already received a COVID-19 vaccine before starting the study. Antibody levels varied depending on the SARS-CoV-2 variant tested (versions of the virus that have enough mutations to behave differently from the original version of the virus).5 What were the side effects?
Different methods for presenting safety data exist. In this summary, we use the method required by the European Medicines Agency for this sort of document. We summarize the side effects that happened during the study. This means that we describe the health problems that people had and that the study doctor thought might be related to the vaccine used in the study. Study results are also presented in other places, and available to the public, using different reference methods.
Side effects are health problems that happen to a study participant during the course of the study. These health problems are called “side effects” because the study doctor thinks they might be related to the medicine used in the study.
How many people had side effects?Part 1: 217 out of 240 participants (90%) in the low antigen quantity group; 214 out of 240 participants (89%) in the medium antigen quantity group; and 218 out of 241 participants (90%) in the high antigen quantity group had any side effects.
Part 2: 686 out of 803 participants (85%) in the MV (D614) group; 577 out of 705 participants (82%) in the MV (B.1.351) group; and 526 out of 621 participants (85%) in the BV (D614+B.1.351) group had any side effects.
Were any of the side effects serious?A side effect is considered serious if it:
• leads to death or is life-threatening, or • causes the study participant to go to the hospital or to stay longer in the hospital, or • causes permanent damage, or • causes a health problem in the pregnant study participant’s baby, or • is considered as an important medical problem putting the study participant in danger.In Part 1 of this study, none of the side effects were considered serious.
In Part 2 of this study, 1 person had a rash and joint pain that were considered serious.What were the most common non-serious side effects?
The tables below show the most common non-serious side effects (those that happened in 5% or more of participants):
Did people stop receiving the vaccine because of a side effect?
In Part 1, none of the participants were stopped from receiving the second vaccination. In Part 2, this was not applicable since the participants received only 1 (booster) dose of the vaccine.What do these results tell us?
Overall, all the CoV2 preS dTM-AS03 study vaccine formulations were safe and well-tolerated.6 How has this study helped people/children?
This study showed that all CoV2 preS dTM-AS03 study vaccine formulations induced antibodies against different SARS-CoV-2 variants. All formulations were safe and well-tolerated in adults.7 Where can I find more information about this study?
Results of clinical studies may be available to the public in different places, and in many countries. As explained in Section 5, study results presented in other places use different reference methods. If you want more information, and if it is available, then you will need to use the study reference numbers. The list below provides those numbers, used by different organizations around the world:
Study number: VAT00002
Sponsor products code: 549 and 561
EudraCT number: 2020-003370-41
National Clinical Trial (NCT) number: NCT04762680 World Health Organization (WHO) Universal Trial Number (UTN): U1111-12514616 You can find out more information in English about this study or its results on the following website(s):
• https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Cleicestercentral.rec%40hra.nhs.uk%7C3af24b855e0840e660fd08dd9d314bc0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638839557233740304%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=hYo3O8gLB4bNNyV%2BWxTPQkl4pvpstOybQr5VQViUv4M%3D&reserved=0 – search for the EudraCT number • https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Cleicestercentral.rec%40hra.nhs.uk%7C3af24b855e0840e660fd08dd9d314bc0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638839557233754341%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=xgb6rJ5oyX8HVEPyJTDT6JqboZbTJ7oTsXCCn3DURIk%3D&reserved=0 - search for the NCT number More information on this study may be found by performing an internet search in available search engine(s), with study identifier VAT00002.8 Who sponsored this study?
Sponsor: Sanofi
How to contact: Contact-Us-PLS@sanofi.com In order to help us manage your email, please include (copy or type) the following information:
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East Midlands - Leicester Central Research Ethics Committee
REC reference
21/EM/0201
Date of REC Opinion
24 Aug 2021
REC opinion
Further Information Favourable Opinion