Clinical trial NCT04864561: COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2 Virus Infection
Keywords: VLA2001
SARS-CoV-2 Virus Infection
COVID-19
inactivated-adjuvanted SARS-CoV-2 virus vaccine
Lead sponsor: Valneva Austria GmbH
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 4034
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
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
timeFrame: Day 43
measure: 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
timeFrame: Day 43
measure: Frequency and severity of any Adverse Events (AE)
timeFrame: Up to Day 43 post-vaccination
Secondary outcomes:
measure: Proportion of adult participants with seroconversion
timeFrame: on Day 8 (age 55+ only), Day 29, Day 71 and Day 208
measure: Proportion of adolescent participants with Seroconversion
timeFrame: on Day 43, Day 71/Day 85 and Day 127
measure: Immune response in adults as determined geometric mean titer (GMT) of SARS-CoV-2-specific neutralising antibodies
timeFrame: on Day 8 (age 55+ only), Day 29, Day 71 and Day 208
measure: Immune response in adolescents as determined by the GMT of SARS-CoV-2-specific neutralising antibodies
timeFrame: on Day 43, Day 71/Day 85 and Day 127
measure: GMT ratio of SARS-CoV-2-specific neutralizing antibodies in the adolescent and adult population
timeFrame: on Day 43
measure: Immune response in adults determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein
timeFrame: on Day 8 (age 55+ only), Day 29, Day 43, Day 71 and Day 208
measure: Immune response in adolescents determined by the GMT of IgG antibodies to SARS-CoV-2 S-protein
timeFrame: on Day 43, Day 71/Day 85 and Day 127
measure: GMT ratio of IgG antibodies to SARS-CoV-2 S-protein in the adolescent and adult population
timeFrame: on Day 43
measure: 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
timeFrame: Adult: Day 29, Day 43, Day 71 and Day 208, Adolescence: on Day 43, Day 71/Day 85 and Day 127
measure: Frequency and severity of solicited injection site and systemic reactions
timeFrame: until 7 days after each and any vaccination
measure: Frequency and severity of any AE
timeFrame: through study completion, up to 13 or 16 months
measure: Frequency and severity of any unsolicited AE
timeFrame: through study completion, up to 13 or 16 months
measure: Frequency and severity of any unsolicited vaccine-related AE
timeFrame: through study completion, up to 13 or 16 months
measure: Frequency and severity of any serious adverse event (SAE)
timeFrame: through study completion, up to 13 or 16 months
measure: Frequency and severity of any adverse event of special interest (AESI)
timeFrame: through study completion, up to 13 or 16 months
measure: Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50 including formal non-inferiority testing on the GMT ratio
timeFrame: on day of booster vaccination, 14 days and 6 months post booster
measure: Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: GMFR with regards to S-protein binding antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: Proportion of participants with 4-fold increase with regards to S-protein binding antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: Assessment of T-cell responses from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot
timeFrame: on day of booster vaccination, 14 days and 6 months post booster
measure: Frequency and severity of solicited injection site and systemic reactions
timeFrame: 7 days after booster vaccination
measure: Frequency and severity of any unsolicited AE
timeFrame: up to 6 months after booster dose
measure: Frequency and severity of any vaccine-related
timeFrame: up to 6 months after booster dose
measure: Frequency and severity of any serious adverse event (SAE)
timeFrame: up to 6 months after booster dose
measure: Frequency and severity of any adverse event of special interest (AESI)
timeFrame: up to 6 months after booster dose
measure: Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: GMT of SARS-CoV-2-specific neutralizing antibodies as measured by MNA50
timeFrame: Day of booser vaccination and 14 days post booster
measure: Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: GMFR with regards to S-protein binding antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: Proportion of participants with 4-fold increase with regards to S-protein binding antibodies
timeFrame: from day of booster vaccination to 14 days after booster vaccination
measure: GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA
timeFrame: Day of booser vaccination and 14 days post booster
measure: Assessment of T-cell responses from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot
timeFrame: Day of booser vaccination and 14 days post booster
measure: Frequency and severity of solicited injection site and systemic reactions
timeFrame: up to 7 days after booster vaccination
measure: Frequency and severity of any unsolicited AE
timeFrame: 180 days post booster vaccination
measure: Frequency and severity of any serious adverse event (SAE)
timeFrame: 180 days post booster vaccination
measure: Frequency and severity of any adverse event of special interest (AESI)
timeFrame: 180 days post booster vaccination
measure: GMT measured as IgG antibodies against SARS-CoV-2 as determined by ELISA
timeFrame: on day of booster vaccination, 14 days and 6 months post booster
measure: Frequency and severity of any vaccine related AE
timeFrame: 180 days post booster vaccination
Other outcomes:
Locations:
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital NHS FT
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge Biomedical Research Centre
city: Cheadle
country: United Kingdom
facility: Cheadle Community Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire
city: Edinburgh
country: United Kingdom
facility: Western General Hospital, Edinburgh - NHS Lothian
city: Epsom
country: United Kingdom
facility: Epsom and St. Helier University Hospitals NHS Trust
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Liverpool
country: United Kingdom
facility: NHS Foundation Trust Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Panthera London
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital, Trust College HOspital NHS Foundation Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Trust
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: NIHR UCLH Clinical Research Facility
city: Newcastle
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Newcastle
city: North Shields
country: United Kingdom
facility: Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital
city: Northampton
country: United Kingdom
facility: Lakeside Healthcare Research
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: University Hospital Plymouth NHS Trust
city: Preston
country: United Kingdom
facility: Panthera Biopartners Preston
city: Rochdale
country: United Kingdom
facility: Panthera Biopartners Manchester
city: Salford
country: United Kingdom
facility: Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust
Study officials:
affiliation: Valneva Austria GmbH
name: Valneva Clinical Development
role: STUDY_CHAIR
References:
citation: 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.