COV-COMPARE Immunogenicity of vaccine VLA2001 compared to AZD1222 [COVID-19] [UPH]
Research type
Research Study
Full title
A RANDOMIZED, OBSERVER-BLIND, CONTROLLED, SUPERIORITY STUDY TO COMPARE THE IMMUNOGENICITY AGAINST COVID-19, OF VLA2001 VACCINE TO AZD1222 VACCINE, IN ADULTS
IRAS ID
294164
Contact name
Adam Finn
Contact email
Sponsor organisation
Valneva Austria GmbH
Eudract number
2021-000522-97
ISRCTN Number
ISRCTN79815558
Duration of Study in the UK
1 years, 1 months, 6 days
Research summary
This study compares the ability of VLA2001 vaccine to generate an adequate immune response to COVID-19, to the AZD1222 vaccine. The aim is to show that VLA2001 is superior to AZD1222. Participants will be adults aged ≥ 18 years of age. The study will run in the UK at approximately 27 sites.
Approximately 3,000 participants 30 years and older will be allocated to receive 2 intramuscular doses of either VLA2001 or AZD1222 at random and overall in a 2:1 ratio. That is 2000 participants to receive VLA2001 and 1000 participants to receive AZD1222 at the recommended dose level, 28 days apart, on Days 1 and 29.
Approximately 1000 participants under 30 years of age will receive VLA2001 at the recommended dose level, 28 days apart, on Days 1 and 29.
For immunogenicity analyses, samples from approximately 1,200 participants (600 per group) who have been tested negative for SARS-CoV-2 at screening will be analysed.
Blood samples will be collected from all participants for safety labs at the screening visit; blood sampling for immunogenicity analyses will take place throughout the study.
Blood samples for PBMC isolation for cellular immunity testing will be selected from 200 participants at approximately 6 sites.
Participants will be provided with an electronic Diary (e-Diary) and will record specifically solicited systemic and local symptoms daily as well as any additional AEs during the 7-day follow-up period after each of both vaccinations and up until Day 43.Participants who think they may have contracted COVID-19 during the study will attend up to 2 COVID-19 verification visits. If COVID-19 infection is confirmed, the participant will attend an unscheduled COVID-19 illness visit during which saliva or a nasal swab will be collected. This will be used to identify the strain of SARS-CoV-2.
Participants will be observed in the study for approximately 12 months.
Primary vaccination (i.e., the 2 first doses 28 days apart) with VLA2001 was generally safe and well- tolerated in adults. After the first vaccination, participants who had received VLA2001 were less likely to suffer from injection site reactions (like injection site pain, tenderness, redness) and systemic reactions (like fatigue, headache, muscle pain, nausea/vomiting or fever) than participants who had received Vaxzevria. After the second and booster vaccination, frequency of these reactions were similar in VLA2001- and Vaxzevria recipients. The vast majority of adverse events was mild or moderate and lasted only for few days. No serious adverse event was caused by the vaccine.
VLA2001 vaccination induced the production of SARS-CoV-2-neutralizing antibodies, which were measured in participants’ blood samples at defined timepoints before and after vaccination. Two weeks after the second vaccinations, antibody levels were higher in blood samples from VLA2001- recipients than in Vaxzevria-recipients. Subsequently, antibody levels decreased over time in both groups, but were still detectable 6 months later. A similar decline of neutralizing antibodies over 6 months post second vaccination had previously been reported for other licensed COVID vaccines.
The booster dose of VLA2001 was also generally safe and well-tolerated both in participants who received VLA2001 and those who received Vaxzevria for primary immunization. The study showed that neutralizing antibody levels increased further after a booster dose with VLA2001. A SARS-CoV-2- specific immune responses persisted up to 6 months post booster.
27% of the adult participants had a PCR-confirmed SARS-CoV-2 infection after the second dose, and 17% of those who received a booster (third) dose, had a PCR-confirmed SARS-CoV-2 infection after their booster dose. Almost all infections were mild or moderate. Only 2 participants had a severe PCR-confirmed SARS-CoV-2 infection: One case occurred 5 months after the second dose of VLA2001, one 6 months after booster vaccination; both cases occurred in participants with comorbidities/risk factors. In adolescents, primary and booster vaccinations with VLA2001 were also generally safe and well- tolerated, and induced a SARS-CoV-2-specific immune response. Unfortunately, the small number of participants does not allow to draw firm conclusions in terms of safety and effectiveness.Primary vaccination (i.e., the 2 first doses 28 days apart) with VLA2001 was generally safe and well- tolerated in adults. After the first vaccination, participants who had received VLA2001 were less likely to suffer from injection site reactions (like injection site pain, tenderness, redness) and systemic reactions (like fatigue, headache, muscle pain, nausea/vomiting or fever) than participants who had received Vaxzevria. After the second and booster vaccination, frequency of these reactions were similar in VLA2001- and Vaxzevria recipients. The vast majority of adverse events was mild or moderate and lasted only for few days. No serious adverse event was caused by the vaccine.
VLA2001 vaccination induced the production of SARS-CoV-2-neutralizing antibodies, which were measured in participants’ blood samples at defined timepoints before and after vaccination. Two weeks after the second vaccinations, antibody levels were higher in blood samples from VLA2001- recipients than in Vaxzevria-recipients. Subsequently, antibody levels decreased over time in both groups, but were still detectable 6 months later. A similar decline of neutralizing antibodies over 6 months post second vaccination had previously been reported for other licensed COVID vaccines.
The booster dose of VLA2001 was also generally safe and well-tolerated both in participants who received VLA2001 and those who received Vaxzevria for primary immunization. The study showed that neutralizing antibody levels increased further after a booster dose with VLA2001. A SARS-CoV-2- specific immune responses persisted up to 6 months post booster.
27% of the adult participants had a PCR-confirmed SARS-CoV-2 infection after the second dose, and 17% of those who received a booster (third) dose, had a PCR-confirmed SARS-CoV-2 infection after their booster dose. Almost all infections were mild or moderate. Only 2 participants had a severe PCR-confirmed SARS-CoV-2 infection: One case occurred 5 months after the second dose of VLA2001, one 6 months after booster vaccination; both cases occurred in participants with comorbidities/risk factors. In adolescents, primary and booster vaccinations with VLA2001 were also generally safe and well- tolerated, and induced a SARS-CoV-2-specific immune response. Unfortunately, the small number of participants does not allow to draw firm conclusions in terms of safety and effectiveness.Lay Summary of Results:
Study informaon
Study VLA2001-301 COV-COMPARE is a clinical study to test the novel COVID-19 vaccine VLA2001 in a
large group of people. In this study, researchers want to learn more about the safety and the ability
of the vaccine to prevent severe COVID-19 by comparing it to the already marketed vaccine Vaxzevria
(AstraZeneca).
Why was the research needed?
Valneva has developed VLA2001, a vaccine for protecting people against coronavirus disease 2019
(COVID-19). The vaccine contains whole particles of the original strain of SARS-CoV-2 (the virus that
causes COVID-19) that has been inactivated (killed) and cannot cause the disease. Researchers
conducted a large-scale study, known as a phase 3 clinical trial, to test the effectiveness and safety of
VLA2001.
What were the main quesons studied?
The main goal of this study was to determine if VLA2001 was at least as effective in protecting from
COVID-19 as another, already available vaccine, for which effectiveness had already been proven
(Vaxzevria – COVID-19 Vaccine AstraZeneca). Protection is known to be strongly associated with the
immune response that can be measured in blood samples in terms of concentrations of antibodies
and of immune cells specific for SARS-CoV-2. Therefore, in this study, researchers compared the
concentration of protective antibodies after participants had received either VLA2001 or Vaxzevria. In
addition, researchers wanted to investigate possible side effects of VLA2001.
Who parcipated in the study?
The study was carried out at 26 clinics in the UK. It involved a significant number of people from
different backgrounds and ages to ensure the vaccine's efficacy across various populaons.
Parcipants had to be healthy or medically stable, such that a worsening of their condion was not
ancipated during the study. The necessary number of parcipants was selected in order to also
enable the detecon of uncommon side effects (occurring only in 0.1% of vaccinees) with a high (94%)
probability.
What treatments did the parcipants take?
4012 adult participants received at least one vaccination in the study. 56% of them were males and
44% were females. 1041 participants were aged between 18 and 29 years, 2947 were between 30 and
55 years, and 24 were above 55 years old.
In addition, 22 participants aged ≥12 to <18 years received at least one vaccination in the study (12
females and 10 males)
Participants aged 30 years received either VLA2001 or Vaxzevria, 2 vaccinations 28 days apart. 1976
participants received VLA2001, and 995 received Vaxzevria.
Participants aged between 18 and 29 years received 2 vaccinations with VLA2001, since at that time
in the UK, Vaxzevria was not recommended for people below 30 years.
958 of the adult participants received a third (booster) dose of VLA2001, 7 to 10 months after the
second dose.
Participants aged ≥12 to <18 years received either VLA2001 or placebo, 2 vaccinations 28 days apart.
Those who received placebo, in addition received first 2 doses of VLA, 8 weeks and 12 weeks after the
Clinical Study Report detail ready for submission to the HRA.
Version 08Sep2023
second placebo dose. 16 participants aged ≥12 to <18 years have received a third (booster) dose of
VLA2001
Participants were asked to report any side effects and other medical occurrences and had several
follow-up visits including medical check-ups and withdrawal of blood samples for the laboratory
analysis of the immune response. Participants were followed up for one year in total. Participants who
received a booster dose were followed up for 6 months after the booster dose.
What were the results of the study?
Primary vaccination (i.e., the 2 first doses 28 days apart) with VLA2001 was generally safe and welltolerated
in adults. After the first vaccination, participants who had received VLA2001 were less likely
to suffer from injection site reactions (like injection site pain, tenderness, redness) and systemic
reactions (like fatigue, headache, muscle pain, nausea/vomiting or fever) than participants who had
received Vaxzevria. After the second and booster vaccination, frequency of these reactions were
similar in VLA2001- and Vaxzevria recipients. The vast majority of adverse events was mild or
moderate and lasted only for few days. No serious adverse event was caused by the vaccine.
VLA2001 vaccination induced the production of SARS-CoV-2-neutralizing antibodies, which were
measured in participants’ blood samples at defined timepoints before and after vaccination. Two
weeks after the second vaccinations, antibody levels were higher in blood samples from VLA2001-
recipients than in Vaxzevria-recipients. Subsequently, antibody levels decreased over time in both
groups, but were still detectable 6 months later. A similar decline of neutralizing antibodies over 6
months post second vaccination had previously been reported for other licensed COVID vaccines.
The booster dose of VLA2001 was also generally safe and well-tolerated both in participants who
received VLA2001 and those who received Vaxzevria for primary immunization. The study showed
that neutralizing antibody levels increased further after a booster dose with VLA2001. A SARS-CoV-2-
specific immune responses persisted up to 6 months post booster.
27% of the adult participants had a PCR-confirmed SARS-CoV-2 infection after the second dose, and
17% of those who received a booster (third) dose, had a PCR-confirmed SARS-CoV-2 infection after
their booster dose. Almost all infections were mild or moderate. Only 2 participants had a severe PCRconfirmed
SARS-CoV-2 infection: One case occurred 5 months after the second dose of VLA2001, one
6 months after booster vaccination; both cases occurred in participants with comorbidities/risk
factors.
In adolescents, primary and booster vaccinations with VLA2001 were also generally safe and welltolerated,
and induced a SARS-CoV-2-specific immune response. Unfortunately, the small number of
participants does not allow to draw firm conclusions in terms of safety and effectiveness.
How has this study helped paents and researchers?
This study has helped to demonstrate the safety and effecveness of the VLA2001 vaccine, in
comparison with another available vaccine, in an adult populaon.
Where can I learn more about this study?
VALNEVA AUSTRIA GMBH
Campus Vienna Biocenter 3, 1030 Vienna, Austria
T +43 1 20620
F +43 1 20620 800
info@valneva.com
Clinical Study Report detail ready for submission to the HRA.
Version 08Sep2023
Addional informaon on VLA2001 can be found here:
hps://www.ema.europa.eu/en/medicines/human/EPAR/covid-19-vaccine-inacvatedadjuvanted-
valneva
hps://valneva.com/category/covid-19/?post_types=press-releaseREC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
21/YH/0151
Date of REC Opinion
22 Apr 2021
REC opinion
Further Information Favourable Opinion