Trial CTRI/2021/10/037066
Publication Thuluva S, Vaccine, 2022
Primary outcome on 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).

Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.

Bias Author's judgement Support for judgement
Randomization
Low 		Quote: “Computer generated randomization.” “After all screening-related activities were completed and prior to the first dose of study vaccine, participants in the study were stratified and randomized to either test or placebo groups in 3:1 ratio according to a random generated codes using the interactive web response system (IWRS) platform.”
Comment: Allocation sequence random.
Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote: “Double-blind. Participants and investigators were blinded to group allocation. Except independent statistician and personnel responsible for conducting packaging/ labelling/blinding of the investigational product, all the personnel involved in the study remained blinded to the study vaccine. The test and placebo were labelled and packed identical to each other.”
Comment: Blinded study (participants and personnel/carers)
Total vaccinated cohort analyzed (ITT).
As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate.
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 624 participants randomized; 624 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Measurement of the outcome
Low 		Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry was available.
Outcomes pre-specified.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias
Low