Inovio Pharmaceuticals Inc (INO)

[Lakers_w]

ISRCTN15779782
https://doi.org/10.1186/ISRCTN15779782
Solidarity trial of candidate vaccines against COVID-19
https://www.isrctn.com/ISRCTN15779782

Primary outcome measure
Virologically confirmed COVID-19 disease, through SARS-CoV2 RNA isolation and RRT-PCR amplification in oro-nasopharyngeal specimen, regardless of disease severity, at 14, 180, 365 days after the last dose.

Secondary outcome measures
Measured at dose 1, dose 2, 7, 180, and 365 days after dose 2:
1. Serious adverse events (SAEs), adverse events of special interest (AESIs) as requested, collected for all participants throughout the study.
2. Severe COVID-19 (as per WHO classification) and death with recently confirmed COVID-19.
3. COVID-19 and severe COVID-19 diagnosed starting 14 days after the final dose through the final study visit.
4. SARS-CoV-2-specific neutralization antibody, binding antibody and T-cell immune responses measured using blood test in a subset of participants at selected sites.
5. COVID-19 viral load and other disease progression biomarkers measured using blood test.

Target number of participants
The trial is endpoint driven, as the main analysis for each vaccine arm versus the concurrent shared placebo/control arm is triggered by occurrence of a total of 150 cases of COVID-19 across these two arms, at which point the results will be reported but blinded follow-up will continue. This fixed num-ber of 150 endpoints is set to provide sufficient power to detect a predefined target level of VE, reject-ing the initially specified null hypothesis that VE is < 30%. For example, for the 150-endpoint design noted above, where a 50:100 vaccine:placebo endpoint split just meets success criteria, if the 6-month COVID-19 attack rate in the placebo arm is 1-2%, and par-ticipants are enrolled evenly over 3 months, then a total evaluable sample size of about 20,000 per vaccine arm, with an equal number in the shared-placebo arm is expected to yield the needed end-points within 2 to 4 months after the median enrolment date.

Publication and dissemination plan
This international collaboration is coordinated through the World Health Organisation, which is also a sponsor of the trial. Any wholly reliable interim findings will be disseminated rapidly by the WHO. There will be group authorship recognizing the contribution of all national and local investigators and guided by the International Committee of Medical Journal Editors (ICMJE) recommendations. Alt-hough the writing committee will consist of the executive group and the WHO trial secretariat, authorship will include all steering committee members and local collaborators whose hospital, in the view of the national principal investigator, contributed substantially towards the trial.

Intervention
Four vaccine candidates selected for evaluation. Candidate vaccines are selected on a rolling basis by the WHO Working Group on vaccine prioritization

Trial entry, randomization: Once electronic data collection has been completed the volunteer automatically enters the trial and a random allocation of their trial vaccine is generated (by an algorithm that ensures eventual balance in the characteristics just recorded between each study vaccines and its placebos) and displayed. The volunteers will be randomly allocated either to placebo or to one of the study vaccines.

Follow-up: Each participant will be contacted weekly for 52 weeks for information as to whether any potentially relevant symptoms have arisen, with laboratory testing triggered if the report suggests COVID-19.

Adaptive design: A global Data Monitoring Committee will keep the accumulating safety results and major outcome results under regular review. Different candidate vaccines may be available or suitable to enter the trial at different times; for each candidate vaccine, the primary efficacy results are expected within 3-6 months of the vaccine entering the trial. By using a shared placebo/control group and a common Core protocol to evaluate multiple candidate vaccines in the trial, resources allocated to the evaluation of each candidate vaccine are judiciously saved while a high standard of scientific rigor and efficiency is ensured.

Add-on studies: Particular countries, or particular groups of sites, may want to collaborate in making further measurements or observations. These could be thought of as Phase 2b trials that are being conducted concurrently with the Phase 3 trial. However, while well-organised additional research studies of additional secondary and supportive endpoints, for which monitoring is valuable but optional at each study site include infection with SARS-CoV-2, trans-mission of SARS-CoV-2, and possible immunological markers as correlates of risk could well be valuable, they are not core requirements in every site.