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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04864561
Other study ID # VLA2001-301
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Completed NCT04671017 - Dose Finding Study to Evaluate The Safety, Tolerability and Immunogenicity of an Inactiviated, Adjuvanted SARS-CoV-2 Virus Vaccine Candidate Against Covid-19 in Healthy Subjects Phase 1/Phase 2
Completed NCT04956224 - Safety and Immunogenicity of VLA2001 Adults Aged ≥56 Years Phase 3