Safety and Immunogenicity of VLA2001 Adults Aged ≥56 Years

SARS-CoV-2 Virus Infection Clinical Trial

Official title:

A Phase III, Open Label, Multicenter, Single Arm Study to Assess the Safety, Tolerability and Immunogenicity of VLA2001 in Volunteers Aged ≥ 56 Years.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04956224
• Other study ID #: VLA2001-304
• Status: Completed
• Phase: Phase 3
• Start date: August 9, 2021
• Est. completion date: November 18, 2022

Study information

• Verified date: August 2023
• Source: Valneva Austria GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a A Phase III, Open label, Multicenter, Single Arm Study to assess the Safety, Tolerability and Immunogenicity of VLA2001 in volunteers aged ≥ 56 years. Approximately 300 participants are enrolled in a non-randomized manner.

Description:

This Phase 3 study is designed as a Multicentre, Open Label, Single Arm Study to assess the Safety, Tolerability and Immunogenicity of VLA2001.

Participants aged 56 years or older and who are either generally healthy or are with a stable medical condition are enrolled.

Approximately 300 participants will be enrolled in a non-randomized manner to receive VLA2001 at the recommended dose level, 28 days apart on Days 1 and 29.

Immunogenicity and safety will be assessed up to month 12 after the first vaccination.

All participants, except those who already received a licensed COVID-19 vaccine outside of the study, will be offered a booster dose with VLA2001. All eligible and willing participants will receive a booster vaccination with VLA2001 and will have a follow-up visit 14 days after the booster dose. The participants will have 1 more follow-up visit 6 months after the booster vaccination which replaces Day 365 for those participants who received a booster dose.

This study will support the VLA2001 safety and immunogenicity database for vaccines aged ≥56 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: November 18, 2022
• Est. primary completion date: November 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 56 Years and older

Eligibility

Inclusion Criteria:

1. All participants must have read, understood, and signed the informed consent form (ICF).

2. Participants of either gender aged 56 years or older at screening.

3. Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up.

4. Participant has a Body Mass Index (BMI) of 18.0-35.0 kg/m2, inclusive, at screening (Visit 0).

5. Must be able to attend all visits of the study and comply with all study procedures, including daily completion of the e-diary for 7 days following each vaccination.

6. Women of childbearing potential (WOCBP), who are sexually active with a man, must be able and willing to use at least 1 highly effective method of contraception (i.e. implant contraceptive, intra-uterine device (IUD) containing either copper or levonorgestrel, male sterilization [vasectomy], female sterilization, injectable contraceptive, oral contraceptive pill, vaginal contraceptive ring, barrier type of birth control measure) from study start until a minimum of 3 months after the last dose of study vaccine (i.e. 3 months after second dose or 3 months after booster dose).

7. 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 last study vaccine administration.

2. History of allergy to any component of the vaccine.

3. History of laboratory-confirmed SARS-CoV infection

4. Participant had close contact to persons with confirmed SARS-CoV-2 infection within 30 days prior to screening.

5. Participant has participated in a clinical study involving an investigational SARS-CoV-2 vaccine or has received or plans to receive a licensed SARS-CoV-2 vaccine during the duration of the study.

6. 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.

7. Participant has a known or suspected defect of the immune system, such as participants with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to the expected day of randomization.

8. 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.

9. History of drug dependency or current use of drug of abuse or alcohol abuse at screening.

10. 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 first vaccination or the booster administration.

11. History of clinically significant bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.

12. Severe and uncontrolled ongoing autoimmune or inflammatory disease, history of Guillain-Barre syndrome or any other demyelinating condition.

13. Any other significant disease, disorder or finding which in the opinion of the investigator may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study.

Prior/concomitant therapy:

14. Receipt of immunoglobulin or another blood product within the 3 months before expected day of first vaccination or the booster administration in this study or those who expect to receive immunoglobulin or another blood product during this study.

15. Receipt of medications and or vaccinations intended to prevent COVID-19.

16. Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine or for medical emergencies such as tetanus or rabies exporsure, within 28 days prior to the expected day of randomization.

Others:

17. Any member of the study team or sponsor.

18. An immediate family member or household member of the study's personnel.

Booster Vaccination in participants 56 years and older:

In addition to the above described eligibility criteria, the following criteria must be met:

1. Participant has not received a licensed COVID-19 vaccine during his/her participation in the study.

Related Conditions & MeSH terms

• SARS-CoV-2 Virus Infection
• Virus Diseases

Intervention

Biological:
• VLA2001
whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide (Wuhan strain) 2 vaccinations 28 days apart Booster Vaccination on Visit B1

Locations

Country	Name	City	State
New Zealand	Southern Clinical Trials Remuera	Auckland	Remuera
New Zealand	Southern Clinical Trials Totara	Auckland	New Lynn
New Zealand	Southern Clinical Trials Waitemata	Auckland	Birkenhead
New Zealand	Southern Clinical Trials Christchurch	Christchurch
New Zealand	Lakeland Clinical Trials Waikato	Hamilton	Nawton
New Zealand	Southern Clinical Trials Tasman	Nelson	Stoke
New Zealand	Lakeland Clinical Trials Culloden	Papamoa	Papamoa Beach
New Zealand	Lakeland Clinical Trials Rotorua	Rotorua

Sponsors (1)

Lead Sponsor	Collaborator
Valneva Austria GmbH

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of any Adverse Events (AE) up to Day 43 post-vaccination		Day 43
Primary	Immune response as determined by the geometric mean titer (GMT) of SARS-CoV-2-specific neutralizing antibodies		Day 43
Primary	Immune response as determined by the seroconversion rate (SCR) of SARS-CoV-2-specific neutralizing antibodies		Day 43
Secondary	Frequency and severity of solicited injection site and systemic reactions after each vaccination		within 7 days
Secondary	Frequency and severity of any unsolicited Adverse Event (AE)		until Day 43
Secondary	Frequency and severity of any unsolicited vaccine-related Adverse Event (AE)		until Day 43
Secondary	Frequency and severity of any Serious Adverse Event (SAE)		until Day 365
Secondary	Frequency and severity of any Adverse Event of Special Interest (AESI)		until Day 365
Secondary	Proportion of participants with Seroconversion after receipt of 2 doses of study vaccination in terms of SARS-CoV-2-specific neutralizing antibodies		on Day 29, Day 57, Day 71 and Day 208
Secondary	Immune response as determined by the Geometric Mean Titer (GMT) of SARS-CoV-2-specific neutralizing antibodies		on Day 29, Day 57, Day 71 and Day 208
Secondary	Proportion of participants with Seroconversion after receipt of 2 doses of study vaccination in terms of S-protein binding IgG levels		on Day 29, Day 57, Day 71 and Day 208
Secondary	Immune response as determined by the Geometric Mean Titer (GMT) of IgG antibodies to SARS-CoV-2 S-protein		on Day 29, Day 57, Day 71 and Day 208
Secondary	Geometric Mean Fold Increase (GMFI) of neutralizing antibody (for binding and neutralizing antibodies)		on Day 29, Day 43, Day 57, Day 71 and Day 208
Secondary	Assessment of T-cell responses from Peripheral Blood Mononuclear Cell (PBMCs) in a subset of participants after in vitro stimulation with SARS-CoV-2 antigens using e.g. ELISpot or intracellular cytokine staining.		on Day 1, Day 43, Day 208, Day 365
Secondary	Frequency and severity of solicited injection site and systemic reactions		within 7 days after booster vaccination
Secondary	Frequency and severity of any unsolicited AE (Adverse Event)		up to 6 months after booster vaccination
Secondary	Frequency and severity of any vaccine-related unsolicited AE (Adverse Event)		up to 6 months after booster vaccination
Secondary	Frequency and severity of any SAE (Serious Adverse Event)		up to 6 months after booster vaccination
Secondary	Frequency and severity of any AESI (Adverse Event of Special Interest)		up to 6 months after booster vaccination
Secondary	Geometric mean fold rise (GMFR) with regards to SARS-CoV-2-specific neutralizing antibodies		from day of booster vaccination up to 14 days after
Secondary	Geometric Mean Titer (GMT) of SARS-CoV-2 specific neutralizing antibodies including formal non-inferiority testing on the GMT ratio for the booster subgroup who had received 2 doses of VLA2001 for primary immunization		on Day 43 and 14 days after booster vaccination
Secondary	Proportion of participants with 4-fold increase with regards to SARS-CoV-2-specific neutralizing antibodies		from day of booster vaccination up to 14 days after
Secondary	Geometric mean fold rise (GMFR) with regards to S-protein binding antibodies		from day of booster vaccination up to 14 days after
Secondary	Proportion of participants with 4-fold increase with regards to S-protein binding antibodies		from day of booster vaccination up to 14 days after
Secondary	Geometric Mean Titer (GMT) measured as IgG antibodies against SARS-CoV-2 as determined by ELISA		from day of booster vaccination up to 6 months after
Secondary	Assessment of T-cell responses from Peripheral Blood Mononuclear Cell (PBMCs) in participants after in vitro stimulation with SARS-CoV-2 antigens using ELISpot		from day of booster vaccination up to 6 months after