COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

NCT04864561 | Completed Phase 3 DMC

• 1 other identifier: VLA2001-301
• Study Type: interventional
• Target: 4,034
• Locations: 1 country
• Sites: 31

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.

Conditions

SARS-CoV-2 Virus Infection

Keywords

VLA2001; SARS-CoV-2 Virus Infection; COVID-19; inactivated-adjuvanted SARS-CoV-2 virus vaccine

Outcome Measures

Primary Outcomes (3)

• 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

• Frequency and severity of any Adverse Events (AE)

  Up to Day 43 post-vaccination

Secondary Outcomes (39)

• Proportion of adult participants with seroconversion

  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

Study Arms (4)

VLA2001

EXPERIMENTAL

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

Biological: VLA2001

AZD1222

ACTIVE COMPARATOR

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

Biological: AZD1222

VLA2001 - adolescent part

EXPERIMENTAL

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

Biological: VLA2001 - adolescent part

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

VLA2001 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

VLA2001

AZD1222 BIOLOGICAL

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

AZD1222

VLA2001 - adolescent part 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.

VLA2001 - adolescent part

Placebo BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.
• History of allergy to any component of the vaccine.
• 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.
• Participant has a known or suspected defect of the immune system
• Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
• History of drug dependency or current use of drug of abuse or alcohol abuse at screening.
• 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).
• History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
• Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.
• 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:
• 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.
• Receipt of medications and or vaccinations intended to prevent COVID-19.
• Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).
• Any member of the study team or sponsor.

Sponsors & Collaborators

• Valneva Austria GmbH: lead

Study Sites (31)

Barnsley Hospital NHS FT

Barnsley, S75 2EP, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2WB, United Kingdom

Location

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, FY3 8NR, United Kingdom

Location

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS2 8DX, United Kingdom

Location

Cambridge Biomedical Research Centre

Cambridge, CB2 0QQ, United Kingdom

Location

Cheadle Community Hospital

Cheadle, ST10 1NS, United Kingdom

Location

University Hospitals Coventry & Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

Western General Hospital, Edinburgh - NHS Lothian

Edinburgh, EH42XU, United Kingdom

Location

Epsom and St. Helier University Hospitals NHS Trust

Epsom, KT187EG, United Kingdom

Location

Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow

Glasgow, G51 4TF, United Kingdom

Location

Royal Surrey County Hospital NHS Foundation Trust

Guildford, GU2 7XX, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, LE39QP, United Kingdom

Location

NHS Foundation Trust Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Barts Health NHS Trust

London, E11BB, United Kingdom

Location

Panthera London

London, EN3 4GS, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

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

London, SE59RS, United Kingdom

Location

Chelsea and Westminster Hospital NHS Trust

London, SW10 9NH, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, SW17 0RE, United Kingdom

Location

NIHR UCLH Clinical Research Facility

London, W1T 7HA, United Kingdom

Location

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

Newcastle, NE1 4LP, United Kingdom

Location

Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital

North Shields, NE29 8NH, United Kingdom

Location

Lakeside Healthcare Research

Northampton, NN17 2UR, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

University Hospital Plymouth NHS Trust

Plymouth, PL6 5FP, United Kingdom

Location

Panthera Biopartners Preston

Preston, PR1 6YA, United Kingdom

Location

Panthera Biopartners Manchester

Rochdale, OL11 4AU, United Kingdom

Location

Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust

Truro, TR13LJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37406777 DERIVED

• 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.

  PMID: 36075233 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

VLA2001 COVID-19 vaccine; ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Study Officials

• Valneva Clinical Development

  Valneva Austria GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: study participants aged 18-29 years at the time of enrolment are unblinded, study participant aged 12-18 and 30 years above at the time of enrolment are blinded (sentinel group is unblinded) until 28 days after vaccination on day 208, when all participants will be unblinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: April 29, 2021
• Study Start: April 26, 2021
• Primary Completion: July 19, 2021
• Study Completion: March 13, 2023
• Last Updated: March 20, 2023

Record last verified: 2023-03

Locations

GB (31)