Clinical Trial to Assess Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Сov-2) Infection

COVID-19 Prevention Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04640233
• Other study ID #: RDI-GCV-001
• Secondary ID: CTRI/2020/11/029
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 30, 2020
• Est. completion date: September 2021

Study information

• Verified date: May 2021
• Source: Dr. Reddy's Laboratories Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects.

Description:

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects.

In phase II trial, 100 subjects of immunogenicity group will be enrolled in 3:1 (Test:Placebo) ratio. These 100 subjects will be assessed for safety and immunogenicity outcomes till Day 28 post the first dose of investigational medicinal product (IMP)/placebo administration and will continue with study assessments till Day 180. Safety and immunogenicity data collected till Day 28 will be submitted to the regulatory authority for recommendation to proceed with Phase III recruitment.

In Phase III trial, 1500 subjects will be enrolled and randomized in the ratio of 3:1 (Gam-COVID--Vac : Placebo).

Each subject will participate in this adaptive study phase II/III clinical trial for 180±14 days after the first dose of the IMP/placebo and will have one screening visit and seven on-site visits during the trial period. The IMP/placebo will be administered intramuscularly during vaccination Visits 1 and 3 (Day 1 and Day 21±2). The observation Visits 2, 4, 5, 6, and 7 will be made on Day 19±2, Day 28±2, Day 42±2, Day 90±7, and Day 180±14, respectively. During the observation visits, vital indicators will be assessed in all subjects and changes in the subjects' condition and well being compared to the previous visit will be recorded. The schedule of examination procedures is mentioned in the Schedule of Event tables.

Additionally, the subjects will be able to have remote consultations with the study physician through the weekly telephonic follow-up.

Blood samples will be taken from immunogenicity group of phase II (all 100) and phase III (284 out of 1500) trials during the following visits to assess the immunogenicity parameters.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1600
• Est. completion date: September 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent of a subject to participate in the trial

2. Males and females aged 18+ years

3. Negative human immunodeficiency virus (HIV 1 & 2) and hepatitis B and C test results

4. Negative immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies through enzyme immunoassay test result

5. Negative COVID-2019 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test result at the screening visit (72 hours prior to Visit 1 [Day 1])

6. No COVID-2019 in the medical history

7. History of no contact with COVID-2019 persons within at least 14 days before the enrolment (according to subjects)

8. Consent for using effective methods of contraception during the entire trial 1

9. Negative urine pregnancy test at the screening visit (for child-bearing age women)

10. No evident vaccine-induced reactions or complications after receiving immunobiological products in the medical history

11. No acute infectious and/or respiratory diseases within at least 14 days before the enrolment.

Exclusion Criteria:

1. Any vaccination/immunization within 30 days before the enrolment

2. Steroids (except hormonal contraceptives) and immunoglobulins or other blood products therapy not finished 30 days before the enrolment

3. Immunosuppressors therapy finished within 3 months before the enrolment

4. Pregnancy or breast-feeding

5. Acute coronary syndrome or stroke suffered less than one year before the enrolment

6. Tuberculosis, chronic systemic infections

7. Drug allergy (anaphylactic shock, Quincke edema, polymorphic exudative eczema, atopy, serum disease),hypersensitivity or allergic reaction to immunobiological products, known allergic reactions to study product components, acute exacerbation of allergic diseases on the enrolment day

8. Subjects who are on drugs that could have potential drug interactions with adenovirus vaccine

9. Medical history of malignancy

10. Donated blood or plasma (450+ mL) within 2 months before the enrolment

11. Splenectomy in the medical history

12. Neutropenia (absolute neutrophil count less than 1,000 mm3), agranulocytosis, significant blood loss,severe anaemia (haemoglobin less than 80 g/L), immunodeficiency including autoimmune disorders in the medical history within 6 months before the enrolment

13. Active form of a disease caused by the HIV and hepatitis B or C

14. Anorexia, protein deficiency of any origin

15. Tattoos at the injection site (deltoid muscle area), which does not allow assessing the local response to the IMP or placebo administration

16. Alcohol or drug addiction in the medical history.

17. Participation in any other interventional clinical trial within 1 month prior to the Screening

18. Any other medical condition that would limit the participation of the subject as per Investigator discretion

19. Study centre staff or other employees directly involved in the trial and their families

20. Subjects contraindicated for vaccination

Related Conditions & MeSH terms

• COVID-19 Prevention
• Infection

Intervention

Biological:
• Gam-COVID-Vac
Vaccine for intramuscular injection

Other:
• Placebo
Placebo comparator

Locations

Country	Name	City	State
India	S N Medical College	Agra
India	MGM Medical College and Hospital	Aurangabad
India	KLE Prabhakar Kore Hospital	Belgaum
India	Apollo Hospital	Delhi
India	Batra Hospital	Delhi
India	HIMSR with CHRD-SAS	Delhi
India	ESIC Medical College & Hospital	Faridabad
India	AIG hospital	Hyderabad
India	Maharaja Agrasen Superspecialty Hospital	Jaipur
India	GSVM Medical College	Kanpur
India	Peerless Hospital	Kolkata
India	Atharva Hospital	Lucknow
India	St. George's Hospital	Mumbai
India	JSS Hospital	Mysore
India	INCLEN trust and Gurunanak Hospital	Palwal
India	PIMS	Puducherry
India	BJ Sassoon Hospital	Pune
India	KEM Hospital	Pune
India	Noble Hospital Private Limited	Pune
India	BAPS hospital	Surat
India	Rhythm Heart Institute	Vadodara
India	Sumandeep Vidyapeeth	Vadodara
India	Christian Medical College	Vellore

Sponsors (4)

Lead Sponsor	Collaborator
Dr. Reddy's Laboratories Limited	CRO: JSS Medical Research India Pvt. Ltd., Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation, Russian Direct Investment Fund

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	For Phase II study - - Incidence & severity of adverse events (AEs) after first dose of IMP/Placebo; For Phase III study -; - Incidence of related serious adverse events (SAEs) following vaccination during the study	For Phase II study - at Day 28; For Phase III study - till day 180 after first dose
Primary	Immunogenicity	For Phase II study -; - Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group	For Phase II study - Day 28 after first dose
Primary	Immunogenicity	For Phase III study - Geometric mean titre ratio of SARS-CoV-2 glycoprotein-specific antibodies between IMP and placebo in immunogenicity group	For Phase III study - Day 42 after first dose
Secondary	Adverse Events	Incidence and severity of adverse events after injecting the first dose of the IMP/placebo; Incidence of SAE following vaccination	Baseline to Day 180
Secondary	Immunogenicity assessment	Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group; Seroconversion rate of SARS-CoV-2 virus-neutralizing antibodies in immunogenicity group	Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180
Secondary	Immunogenicity assessment	Geometric mean virus-neutralizing antibodies titre in immunogenicity group	Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180
Secondary	Immunogenicity assessment	Interferon gamma concentration in T-cells after restimulation with the SARS-CoV-2 glycoprotein in cell mediated immunogenicity group	Baseline, Day 28, Day 42, Day 90 and Day 180
Secondary	Immunogenicity assessment	The number of proliferating cluster of differentiation 4 (CD4) cell and cluster of differentiation 8 (CD8) cells in response to mitogen stimulation in cell mediated immunogenicity group	Baseline, Day 28, Day 42, Day 90 and Day 180
Secondary	Percentage of subjects with mild, moderate, severe coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose of the vaccine/placebo	Comparing percentage of subjects developing COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo based on severity course	Baseline to Day 180
Secondary	Incidence of coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose in trial subjects	Comparing incidence of COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo	Baseline to Day 180