by Bill Snyder
Vanderbilt University Medical Center (VUMC) has been named Data Coordinating Center (DCC) for a nationwide platform of studies aimed at “repurposing” existing drugs to treat mild to moderate symptoms of COVID-19.
The Duke Clinical Research Institute (DCRI) is the Clinical Coordinating Center for the ACTIV-6 platform announced April 19 by the National Institutes of Health (NIH). DCRI has contracted with VUMC for data coordinating services for the studies, which are supported by $155 million in federal funding.
The DCC principal investigator is Chris Lindsell, PhD, professor of Biostatistics and director of the Research Methods Program in the Vanderbilt Institute for Clinical and Translational Research (VICTR), which provides comprehensive support for clinical and translational research at VUMC.
Currently there are no therapies approved specifically to treat mild to moderate COVID-19 symptoms. The goal of ACTIV-6, part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, is to prioritize and speed development of the most promising treatments.
“We have designed the ACTIV-6 platform to make it easy for anyone to take part, no matter where they live,” Lindsell said. “Because we are repurposing existing drugs, it is increasingly possible to deliver research therapies directly to someone’s home.
“Combining easy access to the study with advanced ways of analyzing the data, we will quickly sort through already available, safe drugs to find which ones might help people feel better sooner while also keeping them out of the hospital,” he said.
The National Center for Advancing Translational Sciences (NCATS), part of the NIH, is sponsoring the ACTIV-6 platform with funding from the Biomedical Advanced Research and Development Authority (BARDA) in the Office of the Assistant Secretary for Preparedness and Response, U.S. Department of Health and Human Services.
PCORnet, the National Patient-Centered Clinical Research Network, will support ACTIV-6 governance and operations, and PCORnet sites including VUMC will enroll participants from a broad range of communities. PCORnet funding comes from the Patient-Centered Outcomes Research Institute (PCORI), an independent non-profit research organization.
VICTR has extensive experience with drug repurposing, the use of a drug approved for one disease or condition to treat another.
Supported by NCATS, VICTR’s biostatisticians have been leading the design and analysis of drug repurposing studies at VUMC for the past five years. They have developed novel and efficient approaches to collecting and analyzing the data that “are moving forward the science of doing clinical trials,” Lindsell said. “Leading the ACTIV-6 DCC is the culmination of a lot of hard work laying the foundations.”
DCC co-investigators are Sean Collins, MD, MSci, and Wesley Self, MD, MPH, who helped lead clinical protocol development; Russell Rothman, MD, MPP, PCORnet liaison; Thomas Stewart, PhD, MS, the study’s lead or “blinded” biostatistician; and Frank Harrell PhD, the independent or “unblinded” statistician.
Collins is co-director of the Vanderbilt Coordinating Center (VCC), which provides clinical trials support; Self is VUMC Vice President for Clinical Research Networks and Strategy; and Rothman is VUMC Senior Vice President for Population and Public Health.
Other team members are Jessica Collins, VCC program director; Nicole Zaleski, MA, MPH, VICTR project manager; and Jana Shirey-Rice, PhD, VICTR project management team lead.
The ACTIV-6 protocol will explore a pool of drugs already tested for safety and approved by the U.S. Food and Drug Administration (FDA) for other conditions.
Repurposed drugs that are found to relieve mild to moderate symptoms of COVID-19 could provide treatment options to patients much sooner by avoiding extensive clinical trials testing required of investigational drugs.
ACTIV-6 is a platform trial that uses advanced statistical methods to learn as quickly as possible if there is likely to be any possible gain from using the drug. If there might be some benefit, a drug can continue to be studied if more evidence is needed.
Most of the drugs will be administered orally and will be easy for participants to take at home. Patients will be randomly assigned to receive either the treatments or placebos, which will be sent to them by mail.
If the early data are not promising, then the study can switch it out for a new drug. In this way, the study can sort through a number of possible repurposed drugs to find out which ones might help people feel better sooner and keep the out of the hospital.
Enrollment is expected to open by this summer to participants who are at least 30 years old, have tested positive for infection by SARS-CoV-2, the virus that causes COVID-19, and who have had two or more mild to moderate symptoms of COVID-19 for no more than seven days.
Researchers plan to assess changes in patients’ symptoms over a 14-day period, as well as any hospitalizations and deaths over a 28-day period. Ninety days after treatment begins, the researchers also will assess long-term COVID-19–related symptoms.
A goal is to enable participation by people within communities significantly affected by COVID-19 but who do not have access to major academic medical centers where large clinical trials usually take place.
VUMC has contributed to several other ACTIV initiatives.
Subcontracting with RTI International, a non-profit research organization in North Carolina, VICTR is the Science Unit for the Administrative Coordinating Center of CONNECTS, a national effort that collaborates with the ACTIV program to streamline the research response to life-threatening lung and heart problems caused by COVID-19.
VICTR Director Gordon Bernard, MD, Executive Vice President for Research at VUMC, is the principal investigator of the VUMC Science Unit for CONNECTS, funded by the National Heart, Lung, and Blood Institute of the NIH.
VUMC is participating in the ACTIV-2 protocol to evaluate the safety and efficacy of new potential therapeutics in adult patients with COVID-19 illness who are not hospitalized.
Part of the ACTIV-2 platform of studies, AZD7442, an investigational monoclonal antibody therapy discovered at VUMC and developed by AstraZeneca is now in late-stage clinical trials in the United States and Europe.
PCORnet also facilitates the HERO (Healthcare worker Exposure, Response and Outcomes) program, which includes a registry of health care workers reporting their experiences related to the COVID-19 pandemic, and HERO-Together (www.heroesresearch.org), a study assessing COVID-19 vaccine-related outcomes among health care workers. VUMC remains an active recruitment site for both studies.
Rothman is a member of the PCORnet Executive Steering Committee, co-chair of the HERO Steering Committee, and principal investigator of the PCORI-funded Stakeholders, Technology and Research Clinical Research Network (STAR CRN).
“Our engagement in ACTIV-6 represents a great opportunity for Vanderbilt to once again demonstrate our leadership in designing, conducting and evaluating large pragmatic trials, and to provide important research results that can help us address the COVID-19 pandemic,” Rothman said.
