NIH trial to collect data on tecovirimat (TPOXX).
Interested volunteers can visit the ACTG site for information on the A5418 clinical trial(link is external). Please do not call or email the NIAID News and Science Writing Branch to inquire about enrollment in this trial.
September 9, 2022 – A Phase 3 clinical trial evaluating the antiviral drug tecovirimat, also known as TPOXX, is currently enrolling adults and children infected with monkeypox in the United States. Study researchers aim to recruit more than 500 people from clinical research sites nationwide. Interested volunteers can visit the ACTG website (clinical trial A5418)(link is external) 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(link is external) (ACTG) is leading the study, which may later expand to international sites. The Eunice Kennedy Shriver The NIH’s National Institute of Child Health and Human Development (NICHD) supports multiple sites, including through the International Network for Pediatric Adolescent and Maternal AIDS Clinical Trials (IMPAACT).
Tecovimat, manufactured by the pharmaceutical company SIGA Technologies, Inc., New York City, is approved by the United States Food and Drug Administration for the treatment of smallpox. The drug stops the virus from spreading in the body by preventing virus particles from leaving human cells by targeting a protein found on both the variola virus, which causes smallpox, and the monkeypox virus. Clinicians can currently access tecovirimat for US patients with monkeypox through expanded access or “compassionate use.”(link is external)” application process.
“Monkey pox can be an extremely painful infection that lasts for weeks,” said NIAID Director Anthony S. Fauci, MD. “We currently lack efficacy data that would help us understand the extent to which this drug can alleviate the painful symptoms of monkeypox and prevent serious consequences. This clinical trial was designed to answer these important questions.”
A global outbreak of the human monkeypox virus, first identified in May 2022, prompted public health emergency declarations from the World Health Organization (WHO) and the US Department of Health and of Social Services last summer. The majority of cases identified so far have been in men who have sex with men, although other populations, including women and children, can be infected. From January 1, 2022 to September 7, 2022, WHO reported 52,996 cases and 18 deaths in 102 countries, territories and areas. The Centers for Disease Control and Prevention has reported 21,504 cases in the United States
Prior to the global outbreak, cases and outbreaks of monkeypox were mostly confined to countries in central and western Africa, where the virus is endemic. Monkeypox can cause flu-like symptoms and painful skin lesions. In rare cases, the monkeypox virus can cause serious complications, including dehydration, bacterial infections, pneumonia, brain inflammation, sepsis, eye infections, and death. The virus can be transmitted from person to person through direct contact with broken skin, body fluids, and respiratory droplets, including intimate contact, especially sexual contact, and indirect contact with objects such as contaminated clothing or bedding. Preliminary analyzes indicate that sexual transmission may play a role in the current epidemic.
The US clinical trial of tecovirimat is being led by Timothy Wilkin, MD, professor of medicine at Weill Cornell Medicine in New York. Adults and children of any age with monkeypox are eligible to participate in the trial. Adults with severe monkeypox virus infection or those at high risk of severe disease, including those with underlying immune deficiency, a history of or active inflammatory skin conditions, pregnant women and children, will all be enrolled in an open group in which all participants will receive tecovirimat. Other adult participants – 530 in total – will be randomly assigned in a 2:1 ratio to receive tecovirimat or placebo pills. Tecovirimat capsules are taken orally for 14 days and the dose is based on the participant’s weight. This part of the trial is double-blind, which means that neither the participants nor the investigators will know who is receiving the placebo or the tecovirimat.
Investigators will collect data to determine whether participants given tecovirimat heal faster (all lesions are crusted or flaking off) compared to those taking a placebo. They will also examine the impact of tecovirimat on pain scores, rates of progression to severe disease, clearance of monkeypox virus from various specimens, and its safety, among other data. This study will also provide essential data on the optimal dosage and safety of tecovirimat in children and pregnant women.
Participants will be followed for at least 8 weeks and will be required to complete a symptom diary, perform daily home skin checks, and attend virtual and in-person clinical appointments. They will also undergo physical examinations and be asked to provide samples of blood and other bodily fluids, including fluid from their lesions.
Data on the safety and efficacy of tecovirimat will be submitted to the FDA. An independent Data and Safety Monitoring Board (DSMB) will monitor participant safety throughout the study. The timing of the trial will depend on the pace of registration. This research is supported by the following NIAID grants: UM1AI068636, UM1AI106701, and UM1AI068634, and NICHD contract number HHSN275201800001I.
NIAID is also collaborating with the National Institute for Biomedical Research (INRB) in the Democratic Republic of the Congo to initiate a separate clinical trial of tecovirimat in adults and children with monkeypox in that country. More information about this trial will be available in a future announcement.
NIAID conducts and supports research—at the NIH, in the United States, and around the world—to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets, and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.