US clinical trial evaluating monkeypox antiviral begins

News release

Friday, September 9, 2022

NIH Data Collection Study for Tecoirimate (TPOXX).

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. The researchers aim to enroll more than 500 people from clinical research centers across the country. Interested volunteers can visit the ACTG website (clinical trial A5418) for more information. The study was 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 be expanded to international sites. The Eunice Kennedy Shriver The National Institute of Child Health and Human Development (NICHD) at NIH maintains several sites, including through the International Maternal and Adolescent AIDS Clinical Trials Network (IMPAACT).

Tecovirimat, manufactured by the pharmaceutical company SIGA Technologies, Inc., New York, is approved by the US Food and Drug Administration for the treatment of smallpox. The drug prevents the virus from spreading in the body by preventing virus particles from leaving human cells by targeting a protein found in both the variola virus that causes smallpox and the monkeypox virus. Clinicians currently have access to tecovirimat for US patients with monkeypox 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 alleviate the painful symptoms of monkeypox and prevent serious outcomes.” This clinical trial is designed to answer these important questions.

A global outbreak of the human monkeypox virus, first identified in May 2022, prompted the World Health Organization (WHO) and the US Department of Health and Human Services to declare public health emergencies last summer. The majority of cases identified so far are in men who have sex with men, although other populations, including women and children, can become infected. From 1 January 2022 to 7 September 2022, WHO has reported 52,996 cases and 18 deaths in 102 countries, territories and areas. The Centers for Disease Control and Prevention reported 21,504 cases in the US

Before the global epidemic, monkeypox cases and outbreaks were mostly confined to countries in central and west 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, inflammation of the brain, 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 analyzes suggest that sexual transmission may play a role in the current outbreak.

The clinical trial of tecovirimat in the United States is 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 join the trial. Adults with severe monkeypox virus infection or those at high risk of severe disease, including individuals with hidden immunodeficiency, a history of or active inflammatory skin disease, pregnant people, and children, will all be enrolled in an open arm in which all participants receive tecovirimat. Other adult participants – a total of 530 – will be randomly assigned in a 2:1 ratio to receive tecoxiramit or placebo pills. Tecovirimat capsules are taken orally for 14 days, with the dose based on the participant’s weight. This part of the trial is double-blind, meaning that neither the participants nor the researchers will know who is getting the placebo or tecoxiramit.

The researchers will collect data to determine whether participants who received tecoxiramit healed faster (all lesions covered or peeled off) compared to those who received a placebo. They will also study the impact of tecovirimat on pain outcomes, the rate of progression to severe disease, the clearance of monkeypox virus from different samples and its safety, among other data. This study will also provide critical data on the optimal dosing and safety of tecocirimate in children and pregnant women.

Participants will be followed for at least 8 weeks and will be asked to complete a symptom diary, do daily skin checks at home and attend virtual and in-person clinic appointments. They will also undergo physical examinations and be asked to provide samples of blood and other body fluids, including swab 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 for the duration of the study. Trial schedule will depend on enrollment speed. This research was 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 begin a separate clinical trial of tecorimat in adults and children with monkeypox in that country. More information about this trial will be available in an upcoming announcement.

NIAID conducts and supports research—at NIH, in the United States, and around the world—to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating these diseases. News releases, fact sheets, and other materials related to NIAID are available on the NIAID website.

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