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

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

A multicenter, 3-arm randomized dose finding study in the 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. All participants who receive two doses of the vaccine candidate will be invited to participate in the Booster phase.

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 of the 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.

This study was extended to investigate the tolerability, safety and immungenicity of a booster vaccination with VLA2001. All study participants, in the Booster phase, will be followed up for safety and immunogenicity up to 6 months after receiving their Booster vaccination.

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

1. Participant is 18 to 55 years of age

2. Participant who has a smart phone and is willing and able to install and use the eDiary.

3. Participant 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. Participant is generally healthy as determined by the Investigator

5. Participant has a Body Mass Index (BMI) of 18.0-30.0 kg/m2

6. If subject is of childbearing potential:

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

Inclusion Criteria for Booster Phase - Subjects who meet ALL of the following criteria are eligible for the Booster phase:

• B1. Participant has received complete VLA2001 primary immunization (two vaccinations according to the protocol)

• B2. Participant who has a smart phone and is willing and able to install and use the e-Diary.

• B3. Participant 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.

• B4. Participant is generally healthy as determined by the Investigator's clinical judgement

• B5. If a participant is of childbearing potential:

  1. Participant has a negative urine pregnancy test at Visit 7 prior to booster vaccination.
  2. Participant agrees to employ adequate birth control measures up to 3 months after the Booster vaccination.

Exclusion criteria - Participants 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. Participant had close contact to persons with confirmed SARS-CoV-2 infection within 30 days prior to screening (Visit 0).
4. Participant has participated in a clinical study involving an investigational SARS-CoV-2 vaccine.
5. Participant has an acute or recent infection not due to SARS-CoV-2
6. Participant has a history of SARS-CoV-1 or MERS infection (self-reported)
7. Participant tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
8. Participant has received any vaccine within 30 days prior Visit 1 other than the study intervention, with the exception of the seasonal influenza vaccination.
9. Participant has abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator.
10. Participants 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. Participants with underlying diseases with a high risk of developing severe COVID-19 symptoms if infected
12. 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 subject 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.
13. Participant has a known or suspected defect of the immune system, such as Participants with congenital or acquired immune deficiency
14. Participant received immuno-suppressive therapy within 4 weeks prior to Visit 1 or receipt of immunosuppressive therapy is expected during the study.
15. Participant has a history of any vaccine related contraindicating event
16. Participant presents with clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
17. Participant is pregnant, has plans to become pregnant up to Day 106 of the study or lactating at the time of enrolment.
18. Participant 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. Participant 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. Participant has a rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating.
21. Participant has a known or suspected problem with alcohol or drug abuse as determined by the Investigator.
22. Participant has any condition that, in the opinion of the Investigator, may compromise the Participant's well-being, might interfere with evaluation of study endpoints, or would limit the Participant's ability to complete the study.
23. Participant is committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities).
24. Participant 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. Participant is a member of the team conducting the study or in a dependent relationship with one of the study team members.

Exclusion Criteria for Booster Phase - Participants who meet ANY of the following criteria are NOT eligible for Booster phase:

• B1. Clinically significant infection or other acute illness, including fever ≥ 38°C within 48 hours prior to the planned Booster vaccination.
• B2. Participant has an acute or recent infection not due to SARS-CoV-2 and is not symptom-free in the week prior to the Booster vaccination (Visit 7).
• B3. Participant has received any vaccine within 30 days prior Visit 7, with the exception of the seasonal influenza vaccination. Participants will be encouraged to receive this vaccination at least 7 days after their Booster vaccine.
• B4. Participant has abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) that is considered clinically relevant by the Investigator.
• B5. Participant has received immuno-suppressive therapy within 4 weeks prior to Visit 7 or is expected to receive immunosuppressive therapy during the study. Immunosuppressive therapy is defined as administration of chronic (longer than 2 weeks) prednisone or equivalent ≥ 0.05 mg/kg/day within 4 weeks prior to Visit 7 (topical and inhaled steroids are allowed), radiation therapy or immunosuppressive cytotoxic drugs or monoclonal antibodies in the previous 3 years.
• B6. Participant has clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• B7. Participant is pregnant (positive urine pregnancy test at Visit 7, respectively), has plans to become pregnant up to 3 months after the Booster vaccination.
• B8. Participant has a rash, dermatological condition that would, in the opinion of the Investigator, interfere with injection site reaction rating.
• B9. Participant has a known or suspected problem with alcohol or drug abuse as determined by the Investigator.
• B10. Participant has any condition that, in the opinion of the Investigator, may compromise the Participant's well-being, might interfere with evaluation of study endpoints, or would limit the Participant's ability to complete the study.
• B11. Participant is committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities).
• B12. Participant has participated in another clinical study involving an investigational medicinal product (IMP) or device within 4 weeks prior to Visit 7 or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study.