Covid-19 Living Data

Trial CTRI/2021/10/037066
Publication Thuluva S, Vaccine, 2022

Funding: Mixed (Biological E.Limited, Telangana, India; BIRAC- a division of the Department of Biotechnology, Govt of India; CEPI (Coalition for Epidemic Preparedness Innovation).)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / India Follow-up duration (months): 1.87
	0.5mL BECOV2 12-18 yo. (n = 234) Placebo 12-18 yo. (n = 78) 0.5mL BECOV2 5-12 yo. (n = 234) Placebo 5-12 yo. (n = 78)
Inclusion criteria	Ability to provide written informed consent (by the parents or legally acceptable/authorized representative (LAR) and assent by the children aged between ≥7 to <18 years Subject, in the opinion of the investigator, has ability to communicate and willingness to comply with the requirements of the protocol Participants of either gender of age between <18years to ≥5 (Participant should be <18 years at the time of Screening of the study) Participants virologically seronegative to SARS-CoV-2 infection by RT-PCR and anti-SARS-CoV-2 antibody prior to enrolment Participants considered of stable health as judged by the investigator, determined by medical history and physical examination with normal vital signs as defined in the protocol. [Normal vital sign defined as body temperature <100.4ºF prior to enrolment] Agrees not to participate in another clinical trial at any time during the total study period Agrees to remain in the town where the study centre is located, for the entire duration of the study Willing to allow storage and future use of collected biological samples for future research in an anonymised form.
Exclusion criteria	History of vaccination with any investigational vaccine against COVID-19 disease Seropositive to IgG antibodies against SARS CoV-2 Living in the same household of any COVID-19 positive person Use of any investigational or non-registered product other than the study vaccine during the trial period or 3 months prior to enrolment 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) Current or planned participation in prophylactic drug trials for the duration of the study Known history of HIV 1 & 2, HBV and HCV infection in participants prior to enrolment Body temperature of ≥100.4°F (>38.0°C) or symptoms of an acute illness at the time of screening or prior to vaccination History of severe psychiatric conditions likely to affect participation in the study History of any bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder) History of allergic disease or reactions likely to be exacerbated by any component of the Biological E’s CORBEVAX vaccine formulations Chronic respiratory disease, including asthma Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness Any other serious chronic illness requiring hospital specialist supervision 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. For corticosteroids, this will mean prednisolone ≥0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required) Any medical condition that in the judgment of the investigator would make study participation unsafe Individuals who are part of the study team or close family members of individuals conducting the study Anaphylactic reaction following administration of the investigational vaccine.
Interventions
	Intervention 2 IM doses of 0.5 mL BECOV2, 28 days apart
	Control 2 IM doses adjuvant placebo, 28 days apart2 IM doses adjuvant placebo, 28 days apart
Participants
	Randomized 624 participants
	Characteristics of participants Type of participants: children and adolescents N=624 0 males Children: 858 Immunocompromized patients: 0 Mean age: Age range:
	Description of participants Healthy children and adolescents who were SARS-CoV-2 RT-PCR and anti-SARS-CoV-2 antibody negative in 23 centers in India
Primary outcome
	In the register Phase II: 1. Occurrence of any adverse reactions within 60 minutes of immediate post vaccination period after each dose. 2.The occurrence of solicited symptoms and their severity 7 consecutive days after each dose. 3. The occurrence of any unsolicited adverse events and their severity till 28 days after each post vaccination period. 4. The occurrence and severity of any SAEs or medically attended AEs or AEs of special interest (AESIs) 28 days after each dose. Phase III: 1. Immune response in terms of geometric mean neutralizing titres and their geometric mean fold rise from baseline, at day 42.
	In the report The primary outcome of the phase-2 and secondary outcome of phase-3 part of the study was to assess the safety, tolerability and reactogenicity of CORBEVAX™ vaccine in children and adolescents in comparison to placebo group in terms of occurrence of any solicited and unsolicited AEs for 28 days’ post vaccination. The primary outcome of phase-3 part of the study was demonstration of immunogenic non-inferiority of BE’s CORBEVAX™ vaccine against adult population in terms of geometric mean neutralizing titers and their geometric mean fold rise from baseline, at day 42 (14 days after 2nd dose).
Documents available	Protocol NR Statistical plan * Data-sharing stated: Yes Data accessibility: Additional study data which is not part of the manuscript can be made available upon request and addressed to the corresponding author Dr. Subhash Thuluva at his email subhash.thuluva@biologicale.com
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Low
General comment	In addition to the published article, the trial registry and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The primary and secondary outcomes in the article reflect those in the registry. The trial (n = 624) its target sample size (n = 624). This trial was updated on November 10th 2022, after publication of the study report.