COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222
- Conditions
- SARS-CoV-2 Virus Infection
- Interventions
- Biological: VLA2001Biological: PlaceboBiological: AZD1222Biological: VLA2001 - adolescent part
- Registration Number
- NCT04864561
- Lead Sponsor
- Valneva Austria GmbH
- Brief Summary
This is a multicentre, randomized, observer-blind, active-controlled, superiority, study in adults to compare the immunogenicity of VLA2001 to AZD1222 in terms of GMT of SARS-CoV-2-specific neutralising antibodies. Furthermore, VLA2001 will be compared to placebo in an adolescent population.
- Detailed Description
Approximately 4000 Adult participants will be recruited in the study. About 3000 participants aged 30 years and above will be randomized in a 2:1 ratio to receive 2 intramuscular recommended doses of either VLA2001 (n=2000) or AZD1222 (n=1000). In addition, approximately 1000 subjects aged 18-29 years will participate in this study in a non-randomized, open-label fashion to receive VLA2001. The 2 doses of vaccination for both vaccines will be administered 28 days apart, on Days 1 and 29. All visits will be conducted at the clinical site on an outpatient basis.
All participants - except those who already received a licensed COVID-19 vaccine outside of the study - will be offered a booster dose with VLA2001 between Jan and Mar 2022 and will have a follow-up visit 14 days (Visit B2) and 6months after the booster dose.
Approximately 660 Adolescent participants were planned to be recruited and randomized in a 1:1 ratio to receive 2 intramuscular doses of either VLA2001 (n=330) or placebo (n=300). Participants in the placebo group will receive a 2-dose primary immunization with VLA2001 on Day 85 and the second vaccination 28 days later. For safety reasons, the first 16 adolescents will be enrolled in an open label, non-randomized manner (sentinel dosing).
Recruitment of adolescent participants has been stopped after recruitment of 6 randomized participants (3 randomized to VLA2001 and 3 participants randomized to placebo) due to the low recruitment rate. The study design ensures a safety follow-up of at least 6 months after the last VLA2001 vaccination/booster for all enrolled study participants
Participants will be provided with an electronic Diary (e-Diary) and will be trained to record specifically solicited systemic and local symptoms daily as well as any additional AEs during follow-up period after each of both vaccinations up to the next visit to the site until Day 43 visit has been completed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4034
- Participants must have read, understood, and signed the informed consent form (ICF).
- Participants of either gender aged 12 years and older at screening.
- Medically stable
- Must be able to attend all visits of the study and comply with all study procedures,
- Women of childbearing potential (WOCBP) must be able and willing to use at least 1 highly effective method of contraception for a minimum of 3 months after the last dose of study vaccine.
- WOCBPs must have a negative pregnancy test prior to each vaccination.
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Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.
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History of allergy to any component of the vaccine.
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Significant infection (e.g. positive SARS-CoV-2 RT-PCR) or other acute illness, including fever > 100 °F (> 37.8 °C) 48 hours before vaccination.
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Participant has a known or suspected defect of the immune system
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Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
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Participant has a history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there has been surgical excision or treatment more than 5 years ago that is considered to have achieved a cure, the participant may be enrolled. A history of hematologic malignancy is a permanent exclusion. Participants with a history of skin cancer must not be vaccinated at the previous tumour site.
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History of drug dependency or current use of drug of abuse or alcohol abuse at screening.
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Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma within 6 weeks prior to the expected day of randomization (Visit 1).
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History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
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Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.
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Any other significant disease, disorder or finding which in the opinion of the investigator may significantly increase the risk to the volunteer
Prior/concomitant therapy:
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Receipt of immunoglobulin or another blood product within the 3 months before expected day of randomization (visit 1) in this study or those who expect to receive immunoglobulin or another blood product during this study.
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Receipt of medications and or vaccinations intended to prevent COVID-19.
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Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).
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Any member of the study team or sponsor.
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An immediate family member or household member of the study's personnel.
Booster Vaccination (Adults and Adolescents)
In addition to the above-described eligibility criteria, the following criteria must be met:
- Participant has not received another licensed COVID-19 vaccine during the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VLA2001 VLA2001 \<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222 Placebo Placebo ≥12 to \< 18 years will be randomized 1:1 to receive VLA2001 or Placebo AZD1222 AZD1222 \<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222 VLA2001 - adolescent part VLA2001 - adolescent part ≥12 to \< 18 years will be randomized 1:1 to receive VLA2001 or Placebo
- Primary Outcome Measures
Name Time Method Frequency and severity of any Adverse Events (AE) Up to Day 43 post-vaccination Immune response measured after completion of a 2-dose immunization schedule, as determined by the geometric mean titer (GMT) ratio in adults and GMT in adolescents of SARS-CoV-2-specific neutralizing antibodies Day 43 Immune response measured after completion of a 2-dose immunization schedule, as determined by Seroconversion in adults and adolescents (definded as 4-fold increase from baseline) of SARS-CoV-2-specific neutralizing antibodies Day 43
- Secondary Outcome Measures
Name Time Method Immune response in adults as determined geometric mean titer (GMT) of SARS-CoV-2-specific neutralising antibodies on Day 8 (age 55+ only), Day 29, Day 71 and Day 208 GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50 including formal non-inferiority testing on the GMT ratio on day of booster vaccination, 14 days and 6 months post booster adult participants with single booster
Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies from day of booster vaccination to 14 days after booster vaccination adolescent participants with single booster
Frequency and severity of any unsolicited AE 180 days post booster vaccination adolescent participants with single booster
Immune response in adolescents as determined by the GMT of SARS-CoV-2-specific neutralising antibodies on Day 43, Day 71/Day 85 and Day 127 GMT ratio of SARS-CoV-2-specific neutralizing antibodies in the adolescent and adult population on Day 43 Immune response in adolescents determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein on Day 43, Day 71/Day 85 and Day 127 Frequency and severity of any serious adverse event (SAE) 180 days post booster vaccination adolescent participants with single booster
Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies from day of booster vaccination to 14 days after booster vaccination adolescent participants with single booster
Assessment of T-cell responses from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot Day of booser vaccination and 14 days post booster adolescent participants with single booster
Frequency and severity of any vaccine-related up to 6 months after booster dose adult participants with single booster
Proportion of adolescent participants with Seroconversion on Day 43, Day 71/Day 85 and Day 127 Proportion of adult participants with seroconversion on Day 8 (age 55+ only), Day 29, Day 71 and Day 208 Seroconversion is defined as \>= 4-fold increase in SARS-CoV-2 neutralizing antibody titer against the Wuhan strain and IgG antibodies directed against the S-protein of the Wuhan strain between Day 1 and the defined post-vaccination timepoints
GMFR with regards to S-protein binding antibodies from day of booster vaccination to 14 days after booster vaccination adolescent participants with single booster
Proportion of participants with 4-fold increase with regards to S-protein binding antibodies from day of booster vaccination to 14 days after booster vaccination adolescent participants with single booster
Immune response in adults determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein on Day 8 (age 55+ only), Day 29, Day 43, Day 71 and Day 208 GMT ratio of IgG antibodies to SARS-CoV-2 S-protein in the adolescent and adult population on Day 43 Assessment of T-cell responses from PBMCs on selected time points in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using e.g., ELISpot or intracellular cytokine staining Adult: Day 29, Day 43, Day 71 and Day 208, Adolescence: on Day 43, Day 71/Day 85 and Day 127 Frequency and severity of any AE through study completion, up to 13 or 16 months Frequency and severity of any unsolicited vaccine-related AE through study completion, up to 13 or 16 months Frequency and severity of any vaccine related AE 180 days post booster vaccination adolescent participants with single booster
Frequency and severity of solicited injection site and systemic reactions up to 7 days after booster vaccination adolescent participants with single booster
Frequency and severity of any adverse event of special interest (AESI) 180 days post booster vaccination adolescent participants with single booster
GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50 Day of booser vaccination and 14 days post booster adolescent participants with single booster
GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA on day of booster vaccination, 14 days and 6 months post booster adult participants with single booster
Trial Locations
- Locations (31)
Barnsley Hospital NHS FT
🇬🇧Barnsley, United Kingdom
North Bristol NHS Trust
🇬🇧Bristol, United Kingdom
Cambridge Biomedical Research Centre
🇬🇧Cambridge, United Kingdom
University Hospitals Bristol and Weston NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Cheadle Community Hospital
🇬🇧Cheadle, United Kingdom
University Hospitals Coventry & Warwickshire
🇬🇧Coventry, United Kingdom
Western General Hospital, Edinburgh - NHS Lothian
🇬🇧Edinburgh, United Kingdom
Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow
🇬🇧Glasgow, United Kingdom
Epsom and St. Helier University Hospitals NHS Trust
🇬🇧Epsom, United Kingdom
Royal Surrey County Hospital NHS Foundation Trust
🇬🇧Guildford, United Kingdom
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
NHS Foundation Trust Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Panthera London
🇬🇧London, United Kingdom
Chelsea and Westminster Hospital NHS Trust
🇬🇧London, United Kingdom
King's College Hospital, Trust College HOspital NHS Foundation Trust
🇬🇧London, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Newcastle
🇬🇧Newcastle, United Kingdom
NIHR UCLH Clinical Research Facility
🇬🇧London, United Kingdom
Lakeside Healthcare Research
🇬🇧Northampton, United Kingdom
Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital
🇬🇧North Shields, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
University Hospital Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
Panthera Biopartners Preston
🇬🇧Preston, United Kingdom
Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧Southampton, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Panthera Biopartners Manchester
🇬🇧Rochdale, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Cornwall Hospitals NHS Trust
🇬🇧Truro, United Kingdom
Blackpool Teaching Hospitals NHS Foundation Trust
🇬🇧Blackpool, United Kingdom