The 6th major component of the 1-year old ACTIV public-private initiative of the NIH will test candidate drugs to repurpose for COVID-19.
One year after the NIH announced formation of a public-private partnership to develop treatments for COVID-19, the 6th major research component will commence, with clinical trials to test repurposing of several candidate drugs to treat mild-to-moderate disease and avoid hospitalization.
SInce the NIH announced formation of ACTIV, Accelerating COVID-19 Therapeutic Interventions and Vaccines, in April 2020, the initiative has undertaken 5 major testing and development programs on, respectively: immune modulators; outpatient monoclonal antibodies and other therapies; inpatient monoclonal antibodies and other therapies; antithrombotics; and "big effect" trials, identifying phase 2 trials that evidence promise in late-stage clinical development.
In the most recently announcedACTIV-6 protocol, for platform clinical trials of repurposing approved drugs for outpatients, the candidate agents that demonstrate efficacy in reducing symptoms of mild-to-moderate COVID-19 will be further evaluated for effects on clinical outcomes such as hospitalization and mortality, and long-term COVID-19 symptoms.
"While we're doing a good job with treating hospitalized patients with severe disease, we don't currently have an approved medication that can be self-administered to ease symptoms of people suffering from mild disease at home, and reduce the chance of their needing hospitalization," said NIH Director Francis Collins, MD, PhD, in the announcement."ACTIV-6 will evaluate whether certain drugs showing promise in small trials can pass the rigor of a larger trial."
The ACTIV-6 program, funded by the American Rescue Plan Act, will be overseen by the NIH's National Center for Advancing Translational Sciences (NCATS); with the Duke Clinical Research Institute (DCRI), Durham, North Carolina serving as clinical coordinating center and the Vanderbilt University Medical Center, Nashville, Tennessee serving as the trial data coordinating center.
In an announcement from the DCRI, issued simultaneously with the NIH release,Susanna Naggie, MD, Vice Dean for Clinical Research, Duke University School of Medicine, and the principal investigator who will oversee the coordinating center, described the value of the platform trial, which will enable the concurrent study of up to 7 different drugs that will be selected from a pool of candidates.
"Even with the impressive progress that has been made on vaccines, the pandemic continues to evolve, with new variants and surges of infections in different regions of the world," Naggie stated."Therefore, there remains a critical need for ongoing clinical evidence generation about treatments for COVID-19 in order to meet public health needs, particularly treatments that can be easily administered by patients in their own home."
According to the April 19announcement from the NIH, enrollment in the ACTIV-6 platform trial of drugs to repurpose for COVID-19 is expected to open within a few weeks, for up to 13,500 participants who are at least 30 years old, and have tested positive for SARS-CoV-2 infection, and have experienced two or more mild-to-moderate symptoms of COVID-19 for no more than 7 days.
Researchers will assess changes in patients' symptoms over a 14-day period, as well as hospitalizations and deaths over a 28-day period.They will also assess long-term COVID-19 related symptoms at 90 days after treatment begins.Although the drugs to be tested have not been finalized, the announcement indicates that all will have established safety records, as well as early indications of potential effectiveness against COVID-19 from smaller or less controlled studies.
The ACTIV-6 platform trial will also focus on enrollment of people within minority, rural, or other communities that are significantly affected by COVID-19 but lack access to major academic medical centers that are the usual sites for large clinical trials.