ACTIV-2: A Platform Trial for the Evaluation of Novel Therapeutics for the Treatment of Early COVID-19 in Outpatients

In April of 2020, the public-private partnership, Accelerating COVID-19 Therapeutics and Vaccine (ACTIV), a cross National Institutes of Health (NIH) initiative, was created to jumpstart the evaluation of new therapeutics and vaccines for coronavirus disease 2019 (COVID-19) in randomized clinical trials. The process through which the ACTIV trials were developed and the rationale for the use of a master protocol for this purpose has been previously described. The ACTIV-2 trial was initiated to address the need to evaluate monoclonal antibodies and other novel therapies for ambulatory patients with COVID-19, and the AIDS Clinical Trials Group (ACTG) was selected by the NIH and the ACTIV Therapeutics Working Group to lead the protocol development and study conduct. The goal was to develop a platform trial that could rapidly evaluate compounds that were prioritized for study by the ACTIV agent prioritization group. The clinical trial was sponsored by the NIH and designed and led by a team of investigators in the ACTG with funding to the ACTG UM1 awards. The time from concept submission for ACTIV-2 to the first participant enrolled was 2.5 months. The study team worked in collaboration with pharmaceutical companies who were developing the products; however, all aspects of the trial were under the primary sponsorship of the NIH. A clinical research organization (CRO), PPD, was contracted by the NIH to support the ACTG in the implementation of the trial. This supplement includes papers that describe selected key findings and study design and analysis challenges. In this overview, we provide a description of the ACTIV-2 trial and highlight key operational challenges.