COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

SARS-CoV-2 Virus Infection Clinical Trial

— COV-COMPARE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04864561
• Other study ID #: VLA2001-301
• Status: Completed
• Phase: Phase 3
• Start date: April 26, 2021
• Est. completion date: March 13, 2023

Study information

• Verified date: March 2023
• Source: Valneva Austria GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4034
• Est. completion date: March 13, 2023
• Est. primary completion date: July 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• SARS-CoV-2 Virus Infection
• Virus Diseases

Intervention

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
• AZD1222
2 vaccinations 28 days apart AZD1222 is a recombinant, replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 S surface glycoprotein.
• 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
2 vaccinations 28 days apart with placebo (PBS buffer based on Dulbecco's PBS media formulation without Calcium and Magnesium )

Locations

Country	Name	City	State
United Kingdom	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	Chelsea and Westminster Hospital NHS Trust	London
United Kingdom	King's College Hospital, Trust College HOspital NHS Foundation Trust	London
United Kingdom	NIHR UCLH Clinical Research Facility	London
United Kingdom	Panthera London	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	St George's University Hospitals NHS Foundation Trust	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

Sponsors (1)

Lead Sponsor	Collaborator
Valneva Austria GmbH

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Frequency and severity of any Adverse Events (AE)		Up to Day 43 post-vaccination
Secondary	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
Secondary	Proportion of adolescent participants with Seroconversion		on Day 43, Day 71/Day 85 and Day 127
Secondary	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
Secondary	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
Secondary	GMT ratio of SARS-CoV-2-specific neutralizing antibodies in the adolescent and adult population		on Day 43
Secondary	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
Secondary	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
Secondary	GMT ratio of IgG antibodies to SARS-CoV-2 S-protein in the adolescent and adult population		on Day 43
Secondary	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
Secondary	Frequency and severity of solicited injection site and systemic reactions		until 7 days after each and any vaccination
Secondary	Frequency and severity of any AE		through study completion, up to 13 or 16 months
Secondary	Frequency and severity of any unsolicited AE		through study completion, up to 13 or 16 months
Secondary	Frequency and severity of any unsolicited vaccine-related AE		through study completion, up to 13 or 16 months
Secondary	Frequency and severity of any serious adverse event (SAE)		through study completion, up to 13 or 16 months
Secondary	Frequency and severity of any adverse event of special interest (AESI)		through study completion, up to 13 or 16 months
Secondary	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
Secondary	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
Secondary	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
Secondary	GMFR with regards to S-protein binding antibodies	adult participants with single booster	from day of booster vaccination to 14 days after booster vaccination
Secondary	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
Secondary	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
Secondary	Frequency and severity of solicited injection site and systemic reactions	adult participants with single booster	7 days after booster vaccination
Secondary	Frequency and severity of any unsolicited AE	adult participants with single booster	up to 6 months after booster dose
Secondary	Frequency and severity of any vaccine-related	adult participants with single booster	up to 6 months after booster dose
Secondary	Frequency and severity of any serious adverse event (SAE)	adult participants with single booster	up to 6 months after booster dose
Secondary	Frequency and severity of any adverse event of special interest (AESI)	adult participants with single booster	up to 6 months after booster dose
Secondary	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
Secondary	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
Secondary	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
Secondary	GMFR with regards to S-protein binding antibodies	adolescent participants with single booster	from day of booster vaccination to 14 days after booster vaccination
Secondary	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
Secondary	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
Secondary	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
Secondary	Frequency and severity of solicited injection site and systemic reactions	adolescent participants with single booster	up to 7 days after booster vaccination
Secondary	Frequency and severity of any unsolicited AE	adolescent participants with single booster	180 days post booster vaccination
Secondary	Frequency and severity of any serious adverse event (SAE)	adolescent participants with single booster	180 days post booster vaccination
Secondary	Frequency and severity of any adverse event of special interest (AESI)	adolescent participants with single booster	180 days post booster vaccination
Secondary	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
Secondary	Frequency and severity of any vaccine related AE	adolescent participants with single booster	180 days post booster vaccination