COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

NCT ID: NCT04864561

Last Updated: 2023-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4034 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-26
• Study Completion Date: 2023-03-13

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.

Conditions

SARS-CoV-2 Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

VLA2001

\<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222

Group Type: EXPERIMENTAL

VLA2001

Intervention Type: BIOLOGICAL

whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide 2 vaccinations 28 days apart

AZD1222

\<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222

Group Type: ACTIVE_COMPARATOR

AZD1222

Intervention Type: BIOLOGICAL

2 vaccinations 28 days apart AZD1222 is a recombinant, replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 S surface glycoprotein.

VLA2001 - adolescent part

≥12 to \< 18 years will be randomized 1:1 to receive VLA2001 or Placebo

Group Type: EXPERIMENTAL

VLA2001 - adolescent part

Intervention Type: BIOLOGICAL

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

≥12 to \< 18 years will be randomized 1:1 to receive VLA2001 or Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

2 vaccinations 28 days apart with placebo (PBS buffer based on Dulbecco's PBS media formulation without Calcium and Magnesium )

Interventions

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

Intervention Type: BIOLOGICAL

AZD1222

2 vaccinations 28 days apart AZD1222 is a recombinant, replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 S surface glycoprotein.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Placebo

2 vaccinations 28 days apart with placebo (PBS buffer based on Dulbecco's PBS media formulation without Calcium and Magnesium )

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Valneva Austria GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valneva Clinical Development

Role: STUDY_CHAIR

Valneva Austria GmbH

Locations

Barnsley Hospital NHS FT

Barnsley, , United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, , United Kingdom

North Bristol NHS Trust

Bristol, , United Kingdom

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, , United Kingdom

Cambridge Biomedical Research Centre

Cambridge, , United Kingdom

Cheadle Community Hospital

Cheadle, , United Kingdom

University Hospitals Coventry & Warwickshire

Coventry, , United Kingdom

Western General Hospital, Edinburgh - NHS Lothian

Edinburgh, , United Kingdom

Epsom and St. Helier University Hospitals NHS Trust

Epsom, , United Kingdom

Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow

Glasgow, , 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

Royal Free London NHS Foundation Trust

London, , United Kingdom

King's College Hospital, Trust College HOspital NHS Foundation Trust

London, , United Kingdom

Chelsea and Westminster Hospital NHS Trust

London, , United Kingdom

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

NIHR UCLH Clinical Research Facility

London, , United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Newcastle

Newcastle, , United Kingdom

Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital

North Shields, , United Kingdom

Lakeside Healthcare Research

Northampton, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

University Hospital Plymouth NHS Trust

Plymouth, , United Kingdom

Panthera Biopartners Preston

Preston, , United Kingdom

Panthera Biopartners Manchester

Rochdale, , United Kingdom

Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Royal Cornwall Hospitals NHS Trust

Truro, , United Kingdom

Countries

United Kingdom

References

Taucher C, Lazarus R, Dellago H, Maurer G, Weisova P, Corbic-Ramljak I, Dubischar K, Lilja A, Eder-Lingelbach S, Hochreiter R, Jaramillo JC, Junker H, Krammer M, Pusic P, Querton B, Larcher-Senn J, Hoffmann M, Pohlmann S, Finn A; Valneva Phase 3 Booster Trial Group. Safety and immunogenicity against ancestral, Delta and Omicron virus variants following a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001): Interim analysis of an open-label extension of the randomized, controlled, phase 3 COV-COMPARE trial. J Infect. 2023 Sep;87(3):242-254. doi: 10.1016/j.jinf.2023.06.022. Epub 2023 Jul 3.

Reference Type: DERIVED

PMID: 37406777 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36075233 (View on PubMed)

Other Identifiers

VLA2001-301

Identifier Type: -

Identifier Source: org_study_id