U.S. clinical trial evaluating antiviral for monkeypox begins
A Phase 3 clinical trial evaluating the antiviral tecovirimat, also known as TPOXX, is now enrolling adults and children with monkeypox infection in the United States.
Study investigators aim to enroll more than 500 people from clinical research sites nationwide. Interested volunteers can visit the ACTG website (clinical trial A5418) for more information. The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The NIAID-funded AIDS Clinical Trials Group (ACTG) is leading the study, which may later expand to international sites. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at NIH is supporting several sites, including through the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT).
Tecovirimat, manufactured by the pharmaceutical company SIGA Technologies, Inc., New York City, is approved by the U.S. Food and Drug Administration for the treatment of smallpox. The drug prevents the virus from spreading in the body by preventing virus particles from exiting human cells by targeting a protein found on both the variola virus, which causes smallpox, and the monkeypox virus. Clinicians currently can access tecovirimat for U.S. patients with monkeypox through an expanded access or “compassionate use” request process.
The clinical trial of tecovirimat in the United States is led by Timothy Wilkin, M.D., professor of medicine at Weill Cornell Medicine in New York City. Adults and children of any age with monkeypox are eligible to enroll in the trial. Adults with severe monkeypox virus infection or those at high risk for severe disease including individuals with underlying immune deficiency, a history of or active inflammatory skin conditions, pregnant people and children all will be enrolled in an open-label arm in which all participants receive tecovirimat. Other adult participants—530 total—will be randomly assigned in a 2:1 ratio to receive tecovirimat or placebo pills. Tecovirimat capsules are taken by mouth for 14 days, and the dose is based on the participant’s weight. This part of the trial is double-blind, meaning neither participants nor investigators will know who is receiving placebo or tecovirimat.
Investigators will gather data to determine if participants receiving tecovirimat heal more quickly (all lesions scabbed over or flaked off) compared with those taking placebo. They also will examine tecovirimat’s impact on pain scores, rates of progression to severe disease, clearance of monkeypox virus from various samples, and its safety, among other data. This study also will provide critical data on the optimal dosing and safety of tecovirimat in children and people who are pregnant.
Participants will be followed for at least 8 weeks and will be asked to fill out a symptom diary, do daily skin checks at home and attend virtual and in-person clinic appointments. They also will undergo physical exams and will be asked to provide blood and other bodily fluid samples, including swabbing fluid from their lesions.
