COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222 (COV-COMPARE)

A Randomized, Observer-Blind, Controlled, Superiority Study To Compare The Immunogenicity Against COVID-19, Of VLA2001 Vaccine To AZD1222 Vaccine, In Adults Including a Randomized, Observer-blind, Placebo Controlled Part in Adolescents (≥12 to <18 Years)

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Virus Infection
• Intervention / Treatment: Biological: VLA2001; Biological: AZD1222; Biological: VLA2001 - adolescent part; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 4034
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Barnsley Hospital NHS FT
  • Birmingham, United Kingdom, B15 2WB
    • University Hospitals Birmingham NHS Foundation Trust
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Teaching Hospitals NHS Foundation Trust
  • Bristol, United Kingdom, BS10 5NB
    • North Bristol NHS Trust
  • Bristol, United Kingdom, BS2 8DX
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge Biomedical Research Centre
  • Cheadle, United Kingdom, ST10 1NS
    • Cheadle Community Hospital
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry & Warwickshire
  • Edinburgh, United Kingdom, EH42XU
    • Western General Hospital, Edinburgh - NHS Lothian
  • Epsom, United Kingdom, KT187EG
    • Epsom and St. Helier University Hospitals NHS Trust
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital NHS Foundation Trust
  • Leicester, United Kingdom, LE39QP
    • University Hospitals Of Leicester Nhs Trust
  • Liverpool, United Kingdom, L7 8XP
    • NHS Foundation Trust Royal Liverpool University Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, E11BB
    • Barts Health Nhs Trust
  • London, United Kingdom, EN3 4GS
    • Panthera London
  • London, United Kingdom, SE59RS
    • King's College Hospital, Trust College HOspital NHS Foundation Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital NHS Trust
  • London, United Kingdom, SW17 0RE
    • St George's University Hospitals NHS Foundation Trust
  • London, United Kingdom, W1T 7HA
    • NIHR UCLH Clinical Research Facility
  • Newcastle, United Kingdom, NE1 4LP
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Newcastle
  • North Shields, United Kingdom, NE29 8NH
    • Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital
  • Northampton, United Kingdom, NN17 2UR
    • Lakeside Healthcare Research
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals Nhs Trust
  • Plymouth, United Kingdom, PL6 5FP
    • University Hospital Plymouth NHS Trust
  • Preston, United Kingdom, PR1 6YA
    • Panthera Biopartners Preston
  • Rochdale, United Kingdom, OL11 4AU
    • Panthera Biopartners Manchester
  • Salford, United Kingdom, M6 8HD
    • Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton University Hospitals NHS Trust
  • Truro, United Kingdom, TR13LJ
    • Royal Cornwall Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must have read, understood, and signed the informed consent form (ICF).
2. Participants of either gender aged 12 years and older at screening.
3. Medically stable
4. Must be able to attend all visits of the study and comply with all study procedures,
5. 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.
6. WOCBPs must have a negative pregnancy test prior to each vaccination.

Exclusion Criteria:

1. Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.
2. History of allergy to any component of the vaccine.
3. 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.
4. Participant has a known or suspected defect of the immune system
5. Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
6. 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.
7. History of drug dependency or current use of drug of abuse or alcohol abuse at screening.
8. 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).
9. History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
10. Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.

11. 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:

12. 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.
13. Receipt of medications and or vaccinations intended to prevent COVID-19.
14. Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).
15. Any member of the study team or sponsor.
16. 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:

1. Participant has not received another licensed COVID-19 vaccine during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLA2001; <30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222	Biological: VLA2001; whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide 2 vaccinations 28 days apart
Active Comparator: AZD1222; <30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222	Biological: AZD1222; 2 vaccinations 28 days apart AZD1222 is a recombinant, replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 S surface glycoprotein.
Experimental: VLA2001 - adolescent part; ≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo	Biological: VLA2001 - adolescent part; whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxid 2 vaccinations 28 days apart and with a booster vaccination on day 208. Placebo group will receive VLA2001 on day 208 and following second vaccination 28 days later.
Placebo Comparator: Placebo; ≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo	Biological: Placebo; 2 vaccinations 28 days apart with placebo (PBS buffer based on Dulbecco's PBS media formulation without Calcium and Magnesium )

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Proportion of adult participants with seroconversion	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	on Day 8 (age 55+ only), Day 29, Day 71 and Day 208
Proportion of adolescent participants with Seroconversion		on Day 43, Day 71/Day 85 and Day 127
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
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 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
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
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 solicited injection site and systemic reactions		until 7 days after each and any vaccination
Frequency and severity of any AE		through study completion, up to 13 or 16 months
Frequency and severity of any unsolicited 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 serious adverse event (SAE)		through study completion, up to 13 or 16 months
Frequency and severity of any adverse event of special interest (AESI)		through study completion, up to 13 or 16 months
Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies	adult participants with single booster	from day of booster vaccination to 14 days after booster vaccination
GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50 including formal non-inferiority testing on the GMT ratio	adult participants with single booster	on day of booster vaccination, 14 days and 6 months post booster
Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies	adult participants with single booster	from day of booster vaccination to 14 days after booster vaccination
GMFR with regards to S-protein binding antibodies	adult participants with single booster	from day of booster vaccination to 14 days after booster vaccination
Proportion of participants with 4-fold increase with regards to S-protein binding antibodies	adult participants with single booster	from day of booster vaccination to 14 days after booster vaccination
Assessment of T-cell responses from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot	adult participants with single booster	on day of booster vaccination, 14 days and 6 months post booster
Frequency and severity of solicited injection site and systemic reactions	adult participants with single booster	7 days after booster vaccination
Frequency and severity of any unsolicited AE	adult participants with single booster	up to 6 months after booster dose
Frequency and severity of any vaccine-related	adult participants with single booster	up to 6 months after booster dose
Frequency and severity of any serious adverse event (SAE)	adult participants with single booster	up to 6 months after booster dose
Frequency and severity of any adverse event of special interest (AESI)	adult participants with single booster	up to 6 months after booster dose
Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies	adolescent participants with single booster	from day of booster vaccination to 14 days after booster vaccination
GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50	adolescent participants with single booster	Day of booser vaccination and 14 days post booster
Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies	adolescent participants with single booster	from day of booster vaccination to 14 days after booster vaccination
GMFR with regards to S-protein binding antibodies	adolescent participants with single booster	from day of booster vaccination to 14 days after booster vaccination
Proportion of participants with 4-fold increase with regards to S-protein binding antibodies	adolescent participants with single booster	from day of booster vaccination to 14 days after booster vaccination
GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA	adolescent participants with single booster	Day of booser vaccination and 14 days post booster
Assessment of T-cell responses from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot	adolescent participants with single booster	Day of booser vaccination and 14 days post booster
Frequency and severity of solicited injection site and systemic reactions	adolescent participants with single booster	up to 7 days after booster vaccination
Frequency and severity of any unsolicited AE	adolescent participants with single booster	180 days post booster vaccination
Frequency and severity of any serious adverse event (SAE)	adolescent participants with single booster	180 days post booster vaccination
Frequency and severity of any adverse event of special interest (AESI)	adolescent participants with single booster	180 days post booster vaccination
GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA	adult participants with single booster	on day of booster vaccination, 14 days and 6 months post booster
Frequency and severity of any vaccine related AE	adolescent participants with single booster	180 days post booster vaccination

Collaborators and Investigators

• Sponsor: Valneva Austria GmbH

Publications and helpful links

General Publications

• Lazarus R, Querton B, Corbic Ramljak I, Dewasthaly S, Jaramillo JC, Dubischar K, Krammer M, Weisova P, Hochreiter R, Eder-Lingelbach S, Taucher C, Finn A; Valneva phase 3 trial group. Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial. Lancet Infect Dis. 2022 Dec;22(12):1716-1727. doi: 10.1016/S1473-3099(22)00502-3. Epub 2022 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Actual): July 19, 2021
• Study Completion (Actual): March 13, 2023

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 24, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; VLA2001; SARS-CoV-2 Virus Infection; inactivated-adjuvanted SARS-CoV-2 virus vaccine
• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: VLA2001-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No