A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

Project: Research project

Project Details

Description

Rationale for Proposed Clinical Study
In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in some of these patients. This novel coronavirus has been designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disease caused by this virus has been designated Coronavirus Disease 2019 (COVID-19). There were 59 confirmed cases on January 5, 2020, 278 cases on January 20, 2118 cases on January 26, rising to more than 80,000 confirmed cases and 2,700 deaths as of February 25, 2020 according to various international health reporting agencies. Currently there are no approved therapeutic agents available for coronaviruses.
Study Design
This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 75 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. The initial sample size is calculated to be approximately 440 subjects, and if any additional therapeutic arms are added, the sample size will be recalculated.
Subjects will be assessed daily while hospitalized. Subjects discharged from the hospital will be asked to attend study visits at Days 15 and 29. The Day 22 visit may be conducted by phone. All subjects will undergo a series of efficacy, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to infusion); 3, 5, 8, 11 (while hospitalized); and Day 15 and 29 (if attends an in-person visit or still hospitalized).
The primary outcome evaluates an 8-point ordinal scale (i.e., from death to not hospitalized, no limitations on activities) at Day 15. As little is known about the clinical course of COVID-19, there is uncertainty about the optimal clinical assessment time. Because of this, a pilot study of 100 subjects will be used to evaluate, which day is optimal for assessment. This analysis will be blinded to treatment arm and will inform a decision to keep Day 15 as the timepoint for the primary outcome, or to change it to Day 8, 22 or 29.
StatusActive
Effective start/end date3/22/208/30/20

Funding

  • Leidos Biomedical Research, Inc. (20CTA-DM0006//75N91019D00024 TO 75N9101F00130)
  • National Institute of Allergy and Infectious Diseases (20CTA-DM0006//75N91019D00024 TO 75N9101F00130)

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