A Prospective, multicentre, Phase II Seamlessly Followed by Phase III Clinical Study to Evaluate the Immunogenicity and Safety of Biological E’s CORBEVAX Vaccine for Protection Against COVID-19 Disease When Administered to COVID-19-Negative Adult Subjects.
试验速览
- 阶段
- 2/3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,268
- 试验地点
- 15
- 主要终点
- 1.Proportion of subjects with solicited adverse reactions/symptoms
研究概览
简要总结
This is a prospective, open-label, singlearm, phase II seamlessly followed by Phase III clinical study design toevaluate the immunogenicity and safety of CORBEVAX vaccine for ProtectionAgainst COVID-19 Disease When administered to COVID-19-Negative Adult Subjects between18-80 years of age.
Atotal of 1268 male and non-pregnant female adult, from moderate to high-riskpopulation with and without comorbidities will be enrolled across both phasesof the study. Subjects must be RT-PCR negative to SARS-CoV-2 antigen. A total of 100 subjects, aged 18 to 55 years, will be enrolled in PhaseII for safety assessment and a total of 1168 subjects, aged 18 to 80 years,will be enrolled in Phase III to receive BioE’s SARS-CoV-2 vaccine (CORBEVAX).
The study will be conducted in compliance with GSR 227(E), ICH andIndian good clinical practice guidelines in force at the time of study conduct.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria ONLY for Phase II: 1.Male or female (non-pregnant) subject between ≥ 18 to 55 years of age.
- •2.Subject seronegative to anti-SARS-CoV-2 antibody prior to enrolment.
- •Inclusion Criteria ONLY for Phase III: 1.Male or female subject between ≥ 18 to 80 years of age.
- •Inclusion Criteria for Phase II and Phase III: 1.Subject or their legally acceptable representative (LAR) is willing to provide a written informed consent for voluntary participation in the study.
- •2.Subject, in the opinion of the investigator, has ability to communicate and willingness to comply with the requirements of the protocol.
- •3.Subject is virologically seronegative to SARS-CoV-2 infection as confirmed by RT-PCR prior to enrolment.
- •4.Subject is seronegative to HIV 1 & 2, HBV and HCV infection prior to enrolment.
- •5.Subject is considered of stable health as judged by the investigator, determined by medical history and physical examination.
- •6.Female subject of child bearing potential must have a negative urine pregnancy test (UPT), and willingness to avoid becoming pregnant through use of an effective method of contraception or abstinence from the time of study enrolment until six weeks after the last dose of vaccination in the study.
- •7.Male subject, who is sexually active, must agree to use double-barrier contraception (e.g. condom with spermicide) with his female partner during the study period.
- •Male subject should also agree to avoid semen donation or providing semen for in-vitro fertilization during the study duration.
- •8.Subject agrees not to participate in another clinical trial at any time during the total study period.
- •9.Subject agrees to refrain from blood donation during the course of the study.
- •10.Subject agrees to remain in the town where the study centre is located, for the entire duration of the study.
排除标准
- •1.History of vaccination with any investigational or approved vaccine against COVID-19 disease.
- •2.Subject living in the same household as that of any active COVID-19 positive individual at the time of enrolment.
- •3.History of receipt of any licensed vaccine within 1 month prior to screening, likely to impact on interpretation of the trial data (e.g., influenza vaccines); 4.Subjects with any clinically significant abnormal haematology and biochemical laboratory parameters tested at screening as judged by the investigator.
- •5.Subjects with Body temperature of ≥100.4°F (>38.0°C) or symptoms of an acute illness at the time of screening or prior to vaccination.
- •6.Pregnant women, nursing women or women of childbearing potential who are not actively avoiding pregnancy during the study.
- •7.Subjects with known current or chronic history of any of the following conditions, likely to affect participation in the study: i.severe psychiatric conditions; ii.any bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder); iii.allergic disease or reactions likely to be exacerbated by any component of the study vaccine (BE CORBEVAX vaccine); iv.neurological illness, and any other serious chronic illness requiring hospital specialist supervision.
- •8.Subjects requiring chronic administration (defined as more than 14 days in total) of immunosuppressant (e.g. corticosteroids, cytotoxic drugs or antimetabolites, etc.) or other immune-modifying drugs (e.g. interferons) during the period starting six months prior to the first vaccine dose including use of any blood products.
- •i.For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day, or equivalent.
- •ii.Inhaled and topical steroids are allowed.
- •iii.Receipt of prohibited concomitant medication that may jeopardize the safety of the participant or interpretation of the data.
- •9.Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •10.Any medical condition that in the judgment of the investigator would make study participation unsafe.
- •11.Planned use of any investigational or non-registered product other than the study vaccine during the trial period or 3 months prior to enrolment.
- •13.Individuals who are part of the study team or close family members of individuals conducting the study.
结局指标
主要结局
1.Proportion of subjects with solicited adverse reactions/symptoms
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
2.Proportion of subjects with unsolicited adverse events (AEs)
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
3.Immunogenicity in terms of GMC/T
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
3.SAEs & MAAE in all subjects.
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
1.Anti-RBD IgG antibodies in terms of ratio of IgG1 to IgG4 anti-RBD titres.
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
2.Neutralizing antibody titre
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
4.Proportion of subjects seroconverted in terms of ≥2-fold & ≥4-fold rise
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
5.Cell mediated immunity assessment in terms of cytokine expression from stimulated PBMCs (INF-γ, IL-4)
时间窗: 1.during first 60 minutes of post vaccination and subsequent 7 days. | 2.28-day follow-up period after each dose. | 3.At 6 and 12months post 2nd dose. | 1.at day 42 vs baseline. | 2.at baseline and again at day 42. | 3.at baseline and again at day 42. | 4.in baseline seronegative subjects and ≥2-fold rise in baseline seropositive subjects along with their GMFR at day 42 | 5.at baseline and at day 42
次要结局
- Cell mediated immunity assessment in terms of cytokine expression from stimulated PBMCs (INF-γ, IL-4)(At baseline and at day 42)
- At Phase-III:(Proportion of subjects with solicited adverse reactions/symptoms)
- Proportion of subjects with unsolicited adverse events (AEs)(During the 28-day follow up period after each dose)
- SAEs and MAAES(During the entire study period)
- At Phase-II:(Anti-RBD IgG concentrations (GMC, Fold Rise, GMFR))
- Anti-RBD IgG subclass assessment in terms of ratio of IgG1 to IgG4 titres(At day 42 & day 56.)
- Neutralizing antibody titre(At baseline, day 28, 42, 56 and at 6 and 12 months post second dose.)
- Safety follow-up visit(At 6 and12 months post 2nd dose)