Clinical trial NCT04640233: 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
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID-19 Prevention
Keywords: Sputnik
Gamaleya
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
name: Russian Direct Investment Fund
name: CRO: JSS Medical Research India Pvt. Ltd.
First posted: 2020-11-23
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: For Phase II study - at Day 28; For Phase III study - till day 180 after first dose
measure: Immunogenicity
timeFrame: For Phase II study - Day 28 after first dose
measure: Immunogenicity
timeFrame: For Phase III study - Day 42 after first dose
Secondary outcomes:
measure: Adverse Events
timeFrame: Baseline to Day 180
measure: Immunogenicity assessment
timeFrame: Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180
measure: Immunogenicity assessment
timeFrame: Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180
measure: Immunogenicity assessment
timeFrame: Baseline, Day 28, Day 42, Day 90 and Day 180
measure: Immunogenicity assessment
timeFrame: Baseline, Day 28, Day 42, Day 90 and Day 180
measure: Percentage of subjects with mild, moderate, severe coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose of the vaccine/placebo
timeFrame: Baseline to Day 180
measure: Incidence of coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose in trial subjects
timeFrame: Baseline to Day 180
Other outcomes:
Locations:
city: Agra
country: India
facility: S N Medical College
city: Aurangabad
country: India
facility: MGM Medical College and Hospital
city: Belgaum
country: India
facility: KLE Prabhakar Kore Hospital
city: Delhi
country: India
facility: Apollo Hospital
city: Delhi
country: India
facility: Batra Hospital
city: Delhi
country: India
facility: HIMSR with CHRD-SAS
city: Faridabad
country: India
facility: ESIC Medical College & Hospital
city: Hyderabad
country: India
facility: AIG hospital
city: Jaipur
country: India
facility: Maharaja Agrasen Superspecialty Hospital
city: Kanpur
country: India
facility: GSVM Medical College
city: Kolkata
country: India
facility: Peerless Hospital
city: Lucknow
country: India
facility: Atharva Hospital
city: Mumbai
country: India
facility: St. George's Hospital
city: Mysore
country: India
facility: JSS Hospital
city: Palwal
country: India
facility: INCLEN trust and Gurunanak Hospital
city: Puducherry
country: India
facility: PIMS
city: Pune
country: India
facility: BJ Sassoon Hospital
city: Pune
country: India
facility: KEM Hospital
city: Pune
country: India
facility: Noble Hospital Private Limited
city: Sūrat
country: India
facility: BAPS hospital
city: Vadodara
country: India
facility: Rhythm Heart Institute
city: Vadodara
country: India
facility: Sumandeep Vidyapeeth
city: Vellore
country: India
facility: Christian Medical College
Study officials:
References: