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SARS-CoV-2 Virus InfectionPhase 3COV-COMPARENCT04864561

COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

A Phase 3 study testing VLA2001, AZD1222 and VLA2001 - adolescent part in people with SARS-CoV-2 Virus Infection, run by Valneva Austria GmbH at 31 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and olderHealthy volunteers can take part
Conditions the study is for
SARS-CoV-2 Virus Infection
What is being tested?
VLA2001, AZD1222 and VLA2001 - adolescent part
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
4,034 participants
Where
31 sitesUnited Kingdom
Study dates
26 Apr 2021to 13 Mar 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
  • 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.
  • 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.
  • 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

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United Kingdom31 sites

  • Barnsley Hospital NHS FT

    Barnsley, S75 2EP

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2WB

  • Blackpool Teaching Hospitals NHS Foundation Trust

    Blackpool, FY3 8NR

  • North Bristol NHS Trust

    Bristol, BS10 5NB

  • University Hospitals Bristol and Weston NHS Foundation Trust

    Bristol, BS2 8DX

  • Cambridge Biomedical Research Centre

    Cambridge, CB2 0QQ

  • Cheadle Community Hospital

    Cheadle, ST10 1NS

  • University Hospitals Coventry & Warwickshire

    Coventry, CV2 2DX

  • Western General Hospital, Edinburgh - NHS Lothian

    Edinburgh, EH42XU

  • Epsom and St. Helier University Hospitals NHS Trust

    Epsom, KT187EG

  • Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow

    Glasgow, G51 4TF

  • Royal Surrey County Hospital NHS Foundation Trust

    Guildford, GU2 7XX

  • University Hospitals of Leicester NHS Trust

    Leicester, LE39QP

  • NHS Foundation Trust Royal Liverpool University Hospital

    Liverpool, L7 8XP

  • Barts Health NHS Trust

    London, E11BB

  • Panthera London

    London, EN3 4GS

  • Royal Free London NHS Foundation Trust

    London, NW3 2QG

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

    London, SE59RS

  • Chelsea and Westminster Hospital NHS Trust

    London, SW10 9NH

  • St George's University Hospitals NHS Foundation Trust

    London, SW17 0RE

  • NIHR UCLH Clinical Research Facility

    London, W1T 7HA

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

    Newcastle, NE1 4LP

  • Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital

    North Shields, NE29 8NH

  • Lakeside Healthcare Research

    Northampton, NN17 2UR

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG5 1PB

  • University Hospital Plymouth NHS Trust

    Plymouth, PL6 5FP

  • Panthera Biopartners Preston

    Preston, PR1 6YA

  • Panthera Biopartners Manchester

    Rochdale, OL11 4AU

  • Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust

    Salford, M6 8HD

  • Southampton University Hospitals NHS Trust

    Southampton, SO16 6YD

  • Royal Cornwall Hospitals NHS Trust

    Truro, TR13LJ

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
VLA2001, AZD1222, VLA2001 - adolescent part, Placebo
Keywords
VLA2001, SARS-CoV-2 Virus Infection, COVID-19, inactivated-adjuvanted SARS-CoV-2 virus vaccine
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VLA2001Biological

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

  • AZD1222Biological

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

  • VLA2001 - adolescent partBiological

    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.

  • PlaceboBiological

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

Study groups in NCT04864561
Study groupRoleWhat they receive
VLA2001Experimental<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222
Receives: Biological: VLA2001
AZD1222Active comparator<30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222
Receives: Biological: AZD1222
VLA2001 - adolescent partExperimental≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo
Receives: Biological: VLA2001 - adolescent part
PlaceboPlacebo comparator≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Day 43

  2. 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

    Measured: Day 43

  3. Frequency and severity of any Adverse Events (AE)

    Measured: Up to Day 43 post-vaccination

Secondary outcomes (39)

  1. 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

    Measured: on Day 8 (age 55+ only), Day 29, Day 71 and Day 208

  2. Proportion of adolescent participants with Seroconversion

    Measured: on Day 43, Day 71/Day 85 and Day 127

  3. Immune response in adults as determined geometric mean titer (GMT) of SARS-CoV-2-specific neutralising antibodies

    Measured: on Day 8 (age 55+ only), Day 29, Day 71 and Day 208

  4. Immune response in adolescents as determined by the GMT of SARS-CoV-2-specific neutralising antibodies

    Measured: on Day 43, Day 71/Day 85 and Day 127

  5. GMT ratio of SARS-CoV-2-specific neutralizing antibodies in the adolescent and adult population

    Measured: on Day 43

  6. Immune response in adults determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein

    Measured: on Day 8 (age 55+ only), Day 29, Day 43, Day 71 and Day 208

  7. Immune response in adolescents determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein

    Measured: on Day 43, Day 71/Day 85 and Day 127

  8. GMT ratio of IgG antibodies to SARS-CoV-2 S-protein in the adolescent and adult population

    Measured: on Day 43

  9. 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

    Measured: Adult: Day 29, Day 43, Day 71 and Day 208, Adolescence: on Day 43, Day 71/Day 85 and Day 127

  10. Frequency and severity of solicited injection site and systemic reactions

    Measured: until 7 days after each and any vaccination

  11. Frequency and severity of any AE

    Measured: through study completion, up to 13 or 16 months

  12. Frequency and severity of any unsolicited AE

    Measured: through study completion, up to 13 or 16 months

  13. Frequency and severity of any unsolicited vaccine-related AE

    Measured: through study completion, up to 13 or 16 months

  14. Frequency and severity of any serious adverse event (SAE)

    Measured: through study completion, up to 13 or 16 months

  15. Frequency and severity of any adverse event of special interest (AESI)

    Measured: through study completion, up to 13 or 16 months

  16. Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies

    adult participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  17. 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

    Measured: on day of booster vaccination, 14 days and 6 months post booster

  18. Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies

    adult participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  19. GMFR with regards to S-protein binding antibodies

    adult participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  20. Proportion of participants with 4-fold increase with regards to S-protein binding antibodies

    adult participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  21. 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

    Measured: on day of booster vaccination, 14 days and 6 months post booster

  22. Frequency and severity of solicited injection site and systemic reactions

    adult participants with single booster

    Measured: 7 days after booster vaccination

  23. Frequency and severity of any unsolicited AE

    adult participants with single booster

    Measured: up to 6 months after booster dose

  24. Frequency and severity of any vaccine-related

    adult participants with single booster

    Measured: up to 6 months after booster dose

  25. Frequency and severity of any serious adverse event (SAE)

    adult participants with single booster

    Measured: up to 6 months after booster dose

  26. Frequency and severity of any adverse event of special interest (AESI)

    adult participants with single booster

    Measured: up to 6 months after booster dose

  27. Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies

    adolescent participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  28. GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50

    adolescent participants with single booster

    Measured: Day of booser vaccination and 14 days post booster

  29. Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies

    adolescent participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  30. GMFR with regards to S-protein binding antibodies

    adolescent participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  31. Proportion of participants with 4-fold increase with regards to S-protein binding antibodies

    adolescent participants with single booster

    Measured: from day of booster vaccination to 14 days after booster vaccination

  32. GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA

    adolescent participants with single booster

    Measured: Day of booser vaccination and 14 days post booster

  33. 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

    Measured: Day of booser vaccination and 14 days post booster

  34. Frequency and severity of solicited injection site and systemic reactions

    adolescent participants with single booster

    Measured: up to 7 days after booster vaccination

  35. Frequency and severity of any unsolicited AE

    adolescent participants with single booster

    Measured: 180 days post booster vaccination

  36. Frequency and severity of any serious adverse event (SAE)

    adolescent participants with single booster

    Measured: 180 days post booster vaccination

  37. Frequency and severity of any adverse event of special interest (AESI)

    adolescent participants with single booster

    Measured: 180 days post booster vaccination

  38. GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA

    adult participants with single booster

    Measured: on day of booster vaccination, 14 days and 6 months post booster

  39. Frequency and severity of any vaccine related AE

    adolescent participants with single booster

    Measured: 180 days post booster vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2021
  2. Study start26 Apr 2021
  3. Primary completion19 Jul 2021
  4. Study completion13 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
4,034 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04864561
Sponsor's protocol ID
VLA2001-301
Acronym
COV-COMPARE
Status last verified
Mar 2023
First submitted
23 Apr 2021
Last updated
20 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 37406777

  • 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.

    PubMed 36075233

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing VLA2001, AZD1222 and VLA2001 - adolescent part in people with SARS-CoV-2 Virus Infection, run by Valneva Austria GmbH at 31 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Day 43). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04864561, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2023.

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