Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19 (RESIST)

• ClinicalTrials.gov Identifier: NCT04530396
• Recruitment Status: Active, not recruiting
• First Posted: August 28, 2020
• Last Update Posted: January 22, 2021
• Sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Collaborators: Government of the city of Moscow; CRO: Crocus Medical BV
• Information provided by (Responsible Party): Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

Tracking Information

• First Submitted Date: August 25, 2020
• First Posted Date: August 28, 2020
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: September 7, 2020
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2020)

percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose [ Time Frame: through the whole study, an average of 180 days ]

Demonstrate the superiority of Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the second dose of the study drug/placebo, as confirmed with the method of polymerase chain reaction (PCR)

Original Primary Outcome Measures (submitted: August 27, 2020)

percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose [ Time Frame: through the whole study, an average of 180 days ]

Demonstrate the superiority of Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose of the study drug/placebo, as confirmed with the method of polymerase chain reaction (PCR)

Current Secondary Outcome Measures (submitted: October 23, 2020)

• the severity of the clinical course of COVID-19 [ Time Frame: through the whole study, an average of 180 days ]
  Assess the efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus compared to placebo, based on the severity of the clinical course of COVID-19
• Changing of antibody levels against the SARS-CoV-2 glycoprotein S [ Time Frame: day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose ]
  Assess the immunogenicity of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the geometric mean titer of SARS-CoV-2 glycoprotein-specific antibodies
• Changing of antigen-specific cellular immunity level [ Time Frame: the drug administration day before injecting the first dose of the study drug/placebo and 28±2 days after the first dose ]
  Describe the strength of cell-mediated immune response induced by the use of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo
• Changing of of virus neutralizing antibody titer [ Time Frame: the drug administration day before injecting the first dose of the study drug/placebo and 42±2 days after the first dose ]
  Geometric mean virus-neutralizing antibodies titer
• Incidence of adverse events in trial subjects [ Time Frame: through the whole study, an average of 180 days ]
  Incidence of adverse events in trial subjects compared to placebo
• Severity of adverse events in trial subjects [ Time Frame: through the whole study, an average of 180 days ]
  Severity of adverse events in trial subjects compared to placebo
• estimation of the proportion of study subjects with antibodies to the N-protein of the virus SARS-CoV-2 [ Time Frame: day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose ]
  Percentage of study subjects with antibodies to the N-protein of the SARS - CoV-2 virus that appeared after vaccination

Original Secondary Outcome Measures (submitted: August 27, 2020)

• the severity of the clinical course of COVID-19 [ Time Frame: through the whole study, an average of 180 days ]
  Assess the efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus compared to placebo, based on the severity of the clinical course of COVID-19
• Changing of antibody levels against the SARS-CoV-2 glycoprotein S [ Time Frame: day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose ]
  Assess the immunogenicity of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the geometric mean titer of SARS-CoV-2 glycoprotein-specific antibodies
• Changing of antigen-specific cellular immunity level [ Time Frame: the drug administration day before injecting the first dose of the study drug/placebo and 28±2 days after the first dose ]
  Describe the strength of cell-mediated immune response induced by the use of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo
• Changing of of virus neutralizing antibody titer [ Time Frame: the drug administration day before injecting the first dose of the study drug/placebo and 42±2 days after the first dose ]
  Geometric mean virus-neutralizing antibodies titer
• Incidence of adverse events in trial subjects [ Time Frame: through the whole study, an average of 180 days ]
  Incidence of adverse events in trial subjects compared to placebo
• Severity of adverse events in trial subjects [ Time Frame: through the whole study, an average of 180 days ]
  Severity of adverse events in trial subjects compared to placebo

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19
• Official Title: Randomized Double-blind Placebo-controlled Multi-center Clinical Trial in Parallel Assignment of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine in SARS-СoV-2 Infection Prophylactic Treatment
• Brief Summary: Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment.

Detailed Description

Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment.

The trial will include 40,000 volunteers aged 18+. After screening, they will be randomized (3:1) into two groups - a reference group of 10,000 volunteers receiving placebo and a study group of 30,000 volunteers receiving the Gam-COVID-Vac combined vector vaccine against the SARS-СoV-2-induced coronavirus infection.

The trial subjects will be randomized into five age strata: 18-30, 31-40, 41-50, 51-60, and 60+ years.

The PCR test for SARS-CoV-2 RNA detection at the visit is performed during screening and before the second administration of the vaccine/placebo

Each subject will participate in the trial for 180±14 days after the first dose of the study drug/placebo and will have one screening visit and five on-site visits to the study physician during the said period. The study drug/placebo will be administered intramuscularly during vaccination visits 1 and 2 (day 0 and day 21±2). Subsequent observation visits 3, 4, and 5 will be made on days14±2, 28±2, 35±2,42±2, and 180±14 respectively. During the observation visits, vital signs will be assessed in all trial subjects and changes in the subjects' condition and wellbeing compared to the previous visit will be recorded. Observation visits may be remote, through the telemedicine consultation (TMC).

Additionally, the trial subjects will be able to have remote consultations with the physician through the TMC.

Blood samples will be taken from certain subjects during the following visits to assess the immunogenicity parameters listed below:

Virus-neutralizing activity (300 subjects) ×3 Interferon gamma (107 subjects) ×3 CD4 and CD8 cell count and ratio (50 subjects) SARS-CoV-2 glycoprotein-specific antibodies titer (9,520 subjects) ×3 Determination of the titer of SARS-CoV-2 nucleocleocapsid protein-specific antibodies(9,520 subjects) ×3

Blood sampling will be performed on the day of injecting the first dose of the study drug/placebo immediately prior to the study drug administration Blood sampling for immunogenicity parameters assessment will be only carried out in specially selected study centers.

Blood samples will be taken from 9,520 trial subjects. All four immunogenicity parameters may be assessed in one trial subject.

Trial subjects data will be collected using electronic case report forms and electronic questionnaires to be filled by trial subjects.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized double-blind placebo-controlled

Masking: Double (Participant, Investigator)
Primary Purpose: Prevention

• Condition: Covid19 Prevention

Intervention

• Biological: Gam-COVID-Vac
  vaccine for intramuscular injection
• Other: placebo
  placebo comparator

Study Arms

• Experimental: Primary Group
  Gam-COVID-Vac combined vector vaccine, 0,5ml/dose+0,5 ml/dose prime-boost immunization in days 1 (component I rAd26-S) and 21(component II rAd5-S)
  Intervention: Biological: Gam-COVID-Vac
• Placebo Comparator: Control Group
  placebo, 0,5ml/dose+0,5 ml/dose immunization in days 1 and 21
  Intervention: Other: placebo

• Publications *: Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, Kovyrshina AV, Lubenets NL, Grousova DM, Erokhova AS, Botikov AG, Izhaeva FM, Popova O, Ozharovskaya TA, Esmagambetov IB, Favorskaya IA, Zrelkin DI, Voronina DV, Shcherbinin DN, Semikhin AS, Simakova YV, Tokarskaya EA, Egorova DA, Shmarov MM, Nikitenko NA, Gushchin VA, Smolyarchuk EA, Zyryanov SK, Borisevich SV, Naroditsky BS, Gintsburg AL; Gam-COVID-Vac Vaccine Trial Group. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021 Feb 20;397(10275):671-681. doi: 10.1016/S0140-6736(21)00234-8. Epub 2021 Feb 2. Erratum in: Lancet. 2021 Feb 20;397(10275):670.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 20, 2021): 33758
• Original Estimated Enrollment (submitted: August 27, 2020): 40000
• Estimated Study Completion Date: May 1, 2021
• Estimated Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Written informed consent of a subject to participate in the trial
2. Males and females aged ≥18 y.o.;
3. Negative HIV, hepatitis, and syphilis test results
4. Negative anti-SARS CoV2 IgM and IgG antibodies test carried out with the enzyme immunoassay method
5. Negative COVID-2019 PCR test result at the screening visit
6. No COVID-2019 in the past medical history
7. No contact with COVID-2019 diseased persons within at least 14 days before the enrollment (according to trial subjects)
8. Consent to use effective contraception methods during the trial
9. Negative urine pregnancy test at the screening visit (for child-bearing age women)
10. Negative drugs or psychostimulants urine test at the screening visit
11. Negative alcohol test at the screening visit
12. No evident vaccine-induced reactions or complications after receiving immunobiological products in the past medical history
13. No acute infectious and/or respiratory diseases within at least 14 days before the enrollment.

Exclusion Criteria:

1. Any vaccination/immunization within 30 days before the enrollment;
2. Steroids (except hormonal contraceptives) and/or immunoglobulins or other blood products therapy not finished 30 days before the enrollment
3. Immunosuppressors therapy finished within 3 months before the enrollment
4. Pregnancy or breast-feeding
5. Acute coronary syndrome or stroke suffered less than one year before the enrollment
6. Tuberculosis, chronic systemic infections
7. Drug allergy (anaphylactic shock, Quincke's edema, polymorphic exudative eczema, atopy, serum disease), hypersensitivity or allergic reaction to immunobiological products, known allergic reactions to study drug components, acute exacerbation of allergic diseases on the enrollment day
8. Neoplasms in the past medical history (ICD codes C00-D09)
9. Donated blood or plasma (450+ ml) within 2 months before the enrollment
10. History of splenectomy;
11. Neutropenia (absolute neutrophil count <1,000/mm3), agranulocytosis, significant blood loss, severe anemia (hemoglobin <80 g/L), immunodeficiency in the past medical history within 6 months before the enrollment
12. Active form of a disease caused by the human immunodeficiency virus, syphilis, hepatitis B or C
13. Anorexia, protein deficiency of any origin
14. Big-size tattoos at the injection site (deltoid muscle area), which does not allow assessing the local response to the study drug/placebo administration
15. Alcohol or drug addiction in the past medical history
16. Participation in any other interventional clinical trial
17. Any other condition that the study physician considers as a barrier to the trial completion as per the protocol
18. Study center staff or other employees directly involved in the trial, or their families.

If a subject has any contraindications to vaccination based on the Guidelines on Detection, Investigation and Prevention, of Vaccination-induced Side Reactions (approved by the Ministry of Healthcare of Russia on Apr. 12, 2019, the vaccination may be postponed for a period of time specified in the document.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 111 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT04530396
• Other Study ID Numbers: 04-Gam-COVID-Vac-2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Study Sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

Collaborators

• Government of the city of Moscow
• CRO: Crocus Medical BV

Investigators

• Study Chair: Elena Smolyarchuk, MD, PhD; Study Coordinator
• Study Chair: Sergey Zyryanov, MD, PhD; Study Coordinator

• PRS Account: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Verification Date: August 2020