Dose Finding Study to Evaluate Safety, Tolerability and Immunogenicity of an Inactiviated Adjuvanted Sars-Cov-2 Virus Vaccine Candidate Against Covid-19 in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04671017
• Recruitment Status: Active, not recruiting
• First Posted: December 17, 2020
• Last Update Posted: March 9, 2021
• Sponsor: Valneva Austria GmbH
• Collaborator: National Institute for Health Research, United Kingdom
• Information provided by (Responsible Party): Valneva Austria GmbH

Study Description

Brief Summary:

A multicenter, 3-arm randomized dose finding study in UK to evaluate safety, tolerability and immunogenicity of a vaccine candidate against Covid-19. 150 healthy volunteers will be enrolled and receive two shots of the vaccine candidate.

Condition or disease	Intervention/treatment	Phase
Sars-Cov-2 Virus Infection	Biological: VLA2001	Phase 1; Phase 2

Detailed Description:

The multicenter, dose finding Phase 1/2 study starts off with an open-label, dose-escalation part, thereafter, during the double-blind part of study, participants will be randomized 1:1:1 to receive the low, medium or high dose of the vaccine (VLA2001). All participants will received a total of two vaccinations intramuscularly, on day 1 and day 22.

The first 5 participants in each dose group will receive VLA2001 open label, starting with the low dose of VLA2001. If no safety concerns are identified, the next 5 subjects will receive the medium dose of the vaccine. Again, if no safety issues are identified, 5 participants will be vaccinated with the high dose vaccine. A Data Safety and Monitoring Board (DSMB) will review accrued safety data before randomization of the remaining 135 subjects across all sites will be initiated.

All study participants will be followed up for safety and immunogenicity up to approximately 6 months after receiving their second vaccination.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention Model Description

1. st phase Sequential (open-label randomized phase)
2. nd phase Parallel Assignment (double-blinded randomized phase )

• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

1. st phase is open-label randomized
2. nd phase is double-blind randomized (Participant, Investigator )

• Primary Purpose: Prevention
• Official Title: A Phase I/II Randomized, Two Parts, Dose-Finding Study To Evaluate The Safety, Tolerability and Immunogenicity Of An Inactivated, Adjuvanted Sars-Cov-2 Virus Vaccine Candidate (VLA2001), Against Covid-19 In Healthy Subjects
• Actual Study Start Date: December 16, 2020
• Actual Primary Completion Date: February 26, 2021
• Estimated Study Completion Date: August 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose: VLA2001	Biological: VLA2001; whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phosphor-guanine (CpG) 1018 in combination with aluminium hydroxide
Experimental: Medium Dose: VLA2001	Biological: VLA2001; whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phosphor-guanine (CpG) 1018 in combination with aluminium hydroxide
Experimental: High Dose: VLA2001	Biological: VLA2001; whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phosphor-guanine (CpG) 1018 in combination with aluminium hydroxide

Outcome Measures

Primary Outcome Measures :

1. Frequency and severity of solicited AEs (local and systemic reactions) within 7 days after any vaccination [ Time Frame: until Day 29 ]
2. Geometric mean titre (GMT) for neutralizing antibodies against SARS-CoV-2 [ Time Frame: Day 36 ]

Secondary Outcome Measures :

1. Frequency and severity of any unsolicited AE [ Time Frame: until Day 36 ]
2. Frequency and severity of any vaccine-related AE [ Time Frame: until Day 36 ]
3. Frequency and severity of any AE [ Time Frame: until Day 208 ]
4. Frequency and severity of any vaccine-related AE [ Time Frame: until Day 208 ]
5. Frequency and severity of any SAE [ Time Frame: until Day 36 ]
6. Frequency and severity of any AESI [ Time Frame: until Day 36 ]
7. Frequency and severity of any SAE [ Time Frame: until Day 208 ]
8. Frequency and severity of an AESI [ Time Frame: until Day 208 ]
9. Immune response as measured by neutralizing antibody titres against SARS-CoV-2 [ Time Frame: until Day 208 ]
10. Proportion of subjects with seroconversion in terms of neutralizing antibodies [ Time Frame: until Day 208 ]
11. Fold increase of SARS-CoV-2 neutralizing antibody titres compared with baseline [ Time Frame: until Day 208 ]
12. GMTs for IgG antibodies against SARS-CoV-2 [ Time Frame: until Day 208 ]
13. Proportion of subjects with seroconversion in terms of IgG antibodies against SARS-CoV-2 in subjects negative for SARS-CoV-2 at screening [ Time Frame: until Day 208 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria - Subjects who meet ALL of the following criteria are eligible for the study:

1. Subject is 18 to 55 years of age
2. Subject who has a smart phone and is willing and able to install and use the eDiary.
3. Subject has an understanding of the study and its procedures, agrees to its provisions, and voluntarily gives written informed consent prior to any study-related procedures.
4. Subject is generally healthy as determined by the Investigator
5. Subject has a Body Mass Index (BMI) of 18.0-30.0 kg/m2

6. If subject is of childbearing potential:

   1. Subject has practiced an adequate method of contraception during the 30 days before screening (Visit 0).
   2. Subject has a negative serum or urine pregnancy test at screening (Visit 0) or Visit 1, respectively.
   3. Subject agrees to employ adequate birth control measures up to Day 106 (Visit 5).

Exclusion criteria - Subjects who meet ANY of the following criteria are NOT eligible for this study:

1. Clinically significant infection or other acute illness, including fever ≥ 38°C within 24 hours prior to the planned study vaccination.
2. History of laboratory-confirmed SARS-CoV-2 infection.
3. Subject had close contact to persons with confirmed SARS-CoV-2 infection within 30 days prior to screening (Visit 0).
4. Subject has participated in a clinical study involving an investigational SARS-CoV-2 vaccine.
5. Subject has an acute or recent infection not due to SARS-CoV-2
6. Subject has a history of SARS-CoV-1 or MERS infection (self-reported)
7. Subject tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
8. Subject has received any vaccine within 30 days prior Visit 1 other than the study intervention, with the exception of the seasonal influenza vaccination.
9. Subject has abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator.
10. Subjects with either medical history of or present acute or progressive, unstable or uncontrolled clinical conditions that pose a risk for participation or completion of the study, based on Investigator's clinical judgement.
11. Subjects with underlying diseases with a high risk of developing severe COVID-19 symptoms if infected
12. Subject 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 subject may be enrolled. A history of hematologic malignancy is a permanent exclusion. Subjects with a history of skin cancer must not be vaccinated at the previous tumour site.
13. Subject has a known or suspected defect of the immune system, such as subjects with congenital or acquired immune deficiency
14. Subject received immuno-suppressive therapy within 4 weeks prior to Visit 1 or receipt of immunosuppressive therapy is expected during the study.
15. Subject has a history of any vaccine related contraindicating event
16. Subject presents with clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
17. Subject is pregnant, has plans to become pregnant up to Day 106 of the study or lactating at the time of enrolment.
18. Subject has donated blood, blood fractions or plasma within 4 weeks prior to Visit 1 or received blood-derived products (e.g. plasma) within 12 weeks prior to Visit 1 in this study or plans to donate blood or use blood products during the study.
19. Subject with clinically significant bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder) or prior history of significant bleeding or bruising following IM injections or venepuncture.
20. Subject has a rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating.
21. Subject has a known or suspected problem with alcohol or drug abuse as determined by the Investigator.
22. Subject has any condition that, in the opinion of the Investigator, may compromise the subject's well-being, might interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study.
23. Subject is committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities).
24. Subject has participated in another clinical study involving an investigational medicinal product (IMP) or device within 4 weeks prior to Visit 0 (screening) or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study.
25. Subject is a member of the team conducting the study or in a dependent relationship with one of the study team members.

Contacts and Locations

Locations

United Kingdom

Queen Elizabeth Hospital

Birmingham, United Kingdom, B15 2TH

University Hospital Bristol and Weston NHS Foundation Trust

Bristol, United Kingdom, BS1 3NU

Newcastle University Medical School

Newcastle, United Kingdom, NE7 7DN

Southampton NIHR Clinical Research Facility

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

Valneva Austria GmbH

National Institute for Health Research, United Kingdom

Investigators

• Study Chair: Valneva Clinical Development; Valneva Austria GmbH

More Information

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT04671017
• Other Study ID Numbers: VLA2001-201
• First Posted: December 17, 2020
• Last Update Posted: March 9, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Valneva Austria GmbH:

VLA2001; Sars-Cov-2 Virus Infection; Covid-19; inactivated-adjuvanted Sars-Cov-2 virus vaccine

Additional relevant MeSH terms:

Virus Diseases