Initiation of US clinical trial evaluating monkeypox antiviral agent

press release

Friday 9 September 2022

NIH Study to Collect Data on Tecovirimat (TPOXX).

A phase 3 clinical trial evaluating the antiviral tecovirimate, also known as TPOXX, is now enrolling adults and children with monkeypox infection in the United States. The study researchers plan to enroll more than 500 people from clinical research centers across the country. Interested volunteers can visit the ACTG website (clinical study A5418) for more information. The study 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. That Eunice Kennedy Shriver The NIH’s National Institute of Child Health and Human Development (NICHD) supports multiple sites, including through the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT).

Tecovirimat, manufactured by pharmaceutical company SIGA Technologies, Inc., New York City, is approved by the US Food and Drug Administration for the treatment of smallpox. The drug prevents the virus from spreading through the body by blocking virus particles from leaving human cells by targeting a protein found on both the variola virus, which causes smallpox, and the monkeypox virus. Clinicians currently have access to tecovirimat for monkeypox patients in the United States through an expanded access or compassionate use request process.

“Monkeypox 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 how well this drug can relieve painful monkeypox symptoms and prevent serious outcomes. This clinical study 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 both the World Health Organization (WHO) and the US Department of Health and Human Services last summer. The majority of cases identified to date have involved men who have had 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 have reported 21,504 cases in the United States

Before the global outbreak, monkeypox cases and outbreaks were mainly 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, encephalitis, sepsis, eye infections, and death. The virus can be transmitted from person to person through direct contact with skin lesions, body fluids and respiratory droplets, including through intimate contact, especially sexual contact, and through indirect contact with objects such as contaminated clothing or bedding. Preliminary analysis suggests that sexual transmission may play a role in the current outbreak.

The United States clinical trial of tecovirimat is being led by Timothy Wilkin, MD, Professor of Medicine at Weill Cornell Medicine in New York City. Adults and children of all ages with monkeypox can participate in the study. Adults with severe monkeypox virus infection or those at high risk of severe disease, including those with underlying immunodeficiency, a history of or active inflammatory skin conditions, pregnant women and children will all be enrolled in an open arm where 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. Tecovirimate capsules are taken orally for 14 days, and the dose is based on the participant’s weight. This part of the study is double-blind, meaning neither participants nor investigators know who is receiving placebo or tecovirimat.

Investigators will collect data to determine whether participants who received tecovirimat healed faster (all lesions scabbed or flaked) compared to those who received placebo. They will also examine the effects of tecovirimat on pain scores, rates of progression to serious illness, the elimination of monkeypox virus from various samples, and its safety, among other things. This study will also provide important data on the optimal dosing and safety of tecovirimate in children and pregnant women.

Participants will be observed for at least 8 weeks and asked to fill out a symptom diary, perform daily skin checks at home, and attend virtual and in-person clinic appointments. They will also undergo physical exams and be asked to provide blood and other body fluid samples, including swabs of 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 the safety of participants throughout the duration of the study. The test schedule depends on the sign-up pace. This research is supported by the following NIAID grants: UM1AI068636, UM1AI106701 and UM1AI068634 and NICHD grant number HHSN275201800001I.

NIAID is also working 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 on this study will be available in an upcoming announcement.

NIAID conducts and supports research—at the NIH, in the United States, and worldwide—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):
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 investigating the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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