COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

Valneva Austria GmbH4,034 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

4,034

Conditions

SARS-CoV-2 Virus Infection

Interventions

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.

Eligibility

Sex: ALLMin age: 12 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (31)

Outcomes

Primary Outcomes

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

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

Time frame: Day 43

Frequency and severity of any Adverse Events (AE)

Time frame: Up to Day 43 post-vaccination

Secondary Outcomes

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

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

Proportion of adolescent participants with Seroconversion

Time frame: 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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

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

...and 21 more locations

Time frame: on Day 43

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

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

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

Time frame: on Day 43, Day 71/Day 85 and Day 127

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

Time frame: on Day 43

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

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

Frequency and severity of solicited injection site and systemic reactions

Time frame: until 7 days after each and any vaccination

Frequency and severity of any AE

Time frame: through study completion, up to 13 or 16 months

Frequency and severity of any unsolicited AE

Time frame: through study completion, up to 13 or 16 months

Frequency and severity of any unsolicited vaccine-related AE

Time frame: through study completion, up to 13 or 16 months

Frequency and severity of any serious adverse event (SAE)

Time frame: through study completion, up to 13 or 16 months

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

Time frame: through study completion, up to 13 or 16 months

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

adult participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

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

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

adult participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

GMFR with regards to S-protein binding antibodies

adult participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

adult participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

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

Frequency and severity of solicited injection site and systemic reactions

adult participants with single booster

Time frame: 7 days after booster vaccination

Frequency and severity of any unsolicited AE

adult participants with single booster

Time frame: up to 6 months after booster dose

Frequency and severity of any vaccine-related

adult participants with single booster

Time frame: up to 6 months after booster dose

Frequency and severity of any serious adverse event (SAE)

adult participants with single booster

Time frame: up to 6 months after booster dose

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

adult participants with single booster

Time frame: up to 6 months after booster dose

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

adolescent participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

adolescent participants with single booster

Time frame: Day of booser vaccination and 14 days post booster

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

adolescent participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

GMFR with regards to S-protein binding antibodies

adolescent participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

adolescent participants with single booster

Time frame: from day of booster vaccination to 14 days after booster vaccination

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

adolescent participants with single booster

Time frame: Day of booser vaccination and 14 days post booster

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

Time frame: Day of booser vaccination and 14 days post booster

Frequency and severity of solicited injection site and systemic reactions

adolescent participants with single booster

Time frame: up to 7 days after booster vaccination

Frequency and severity of any unsolicited AE

adolescent participants with single booster

Time frame: 180 days post booster vaccination

Frequency and severity of any serious adverse event (SAE)

adolescent participants with single booster

Time frame: 180 days post booster vaccination

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

adolescent participants with single booster

Time frame: 180 days post booster vaccination

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

adult participants with single booster

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

Frequency and severity of any vaccine related AE

adolescent participants with single booster

Time frame: 180 days post booster vaccination