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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

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ClinicalTrials.gov Identifier: NCT04671017
Recruitment Status : Active, not recruiting
First Posted : December 17, 2020
Last Update Posted : October 29, 2021
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Valneva Austria GmbH

Brief Summary:
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.

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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
  1. st phase Sequential (open-label phase)
  2. nd phase Parallel Assignment (double-blinded randomized phase )
  3. rd phase Parallel Assignment (open-label phase)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
  1. st phase is open-label
  2. nd phase is double-blind randomized (Participant, Investigator )
  3. rd phase is open-label phase
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 : March 31, 2022

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

Experimental: Medium Dose: VLA2001 Biological: VLA2001
whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide

Experimental: High Dose: VLA2001 Biological: VLA2001
whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide

Experimental: Booster: High Dose: VLA2001 Biological: VLA2001
whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide




Primary Outcome Measures :
  1. Frequency and severity of solicited AEs (local and systemic reactions) within 7 days after any vaccination of the primary vaccination series [ Time Frame: until Day 29 ]
  2. Geometric mean titre (GMT) for neutralizing antibodies against SARS-CoV-2 determined by wild-type virus neutralizing assay [ 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. Frequency and severy of solicited AEs (local and systemic reactions) after the booster vaccination [ Time Frame: until Visit 7 plus 6 days ]
  10. Frequency and severity of any unsolicited AE [ Time Frame: until Visit 9 ]
  11. Frequency and severity of any vaccine-related AE [ Time Frame: until Visit 9 ]
  12. Frequency and severity of any SAE [ Time Frame: until Visit 10 ]
  13. Frequency and severity of any AESI [ Time Frame: until Visit 10 ]
  14. Immune response as measured by neutralizing antibody titres against SARS-CoV-2 [ Time Frame: until Day 208 ]
  15. Proportion of Participants with seroconversion in terms of neutralizing antibodies [ Time Frame: until Day 208 ]
  16. Fold increase of SARS-CoV-2 neutralizing antibody titres compared with baseline [ Time Frame: until Day 208 ]
  17. GMTs for IgG antibodies against SARS-CoV-2 determined by ELISA [ Time Frame: until Day 208 ]
  18. Proportion of Participants with seroconversion in terms of IgG antibodies against SARS-CoV-2, as determined by ELISA in Participants negative for SARS-CoV-2 at screening [ Time Frame: until Day 208 ]
  19. Geometric mean fold rise (GMFR) from pre-booster time point (Visit 7) to 2 weeks after booster dose with regards to neutralizing antibodies [ Time Frame: until Visit 8 ]
  20. Geometric mean fold rise (GMFR) from pre-booster time point (Visit 7) to 4 weeks after booster dose with regards to neutralizing antibodies [ Time Frame: until Visit 9 ]
  21. Proportion of Participants with 4-fold increase from pre-booster time point (Visit 7) to 2 weeks after booster dose with regards to neutralizing antibodies [ Time Frame: until Visit 8 ]
  22. Proportion of Participants with 4-fold increase from pre-booster time point (Visit 7) to 4 weeks after booster dose with regards to neutralizing antibodies [ Time Frame: until Visit 9 ]
  23. Geometric mean titres (GMT) measured as neutralizing antibody titres against SARSCoV-2 [ Time Frame: until Visit 9 ]
  24. Geometric mean fold rise (GMFR) from pre-booster time point (Visit 7) to 2 weeks after booster dose with regards to S-protein binding antibodies (ELISA) [ Time Frame: until Visit 8 ]
  25. Geometric mean fold rise (GMFR) from pre-booster time point (Visit 7) to 4 weeks after booster dose with regards to S-protein binding antibodies (ELISA) [ Time Frame: until Visit 9 ]
  26. Proportion of Participants with 4-fold increase from pre-booster time point (Visit 7) to 2 weeks after booster dose in regards to S-protein binding antibodies (ELISA) [ Time Frame: until Visit 8 ]
  27. Proportion of Participants with 4-fold increase from pre-booster time point (Visit 7) to 4 weeks after booster dose in regards to S-protein binding antibodies (ELISA) [ Time Frame: until Visit 9 ]
  28. Geometric mean titres (GMT) measured as IgG antibodies against SARS-CoV-2 (ELISA [ Time Frame: until Visit 9 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04671017


Locations
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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
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Study Chair: Valneva Clinical Development Valneva Austria GmbH
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Responsible Party: Valneva Austria GmbH
ClinicalTrials.gov Identifier: NCT04671017    
Other Study ID Numbers: VLA2001-201
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: October 29, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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COVID-19
Virus Diseases
Infections
Respiratory Tract Infections
Pneumonia, Viral
Pneumonia
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases