The STOMP study found tecovirimat safe but ineffective in reducing lesion resolution or pain in adults with mild to moderate clade II mpox.

An interim analysis of the international clinical trial, the Study of Tecovirimat for Mpox (STOMP), revealed that the antiviral drug tecovirimat did not shorten the time to lesion healing or alleviate pain in adults with mild to moderate clade II mpox and a low risk of severe disease. The analysis identified no safety concerns related to tecovirimat (1^✔ ✔Trusted Source
Assessment of the Efficacy and Safety of Tecovirimat in Patients with Monkeypox Virus Disease (UNITY)

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In light of these conclusive findings, the study’s Data Safety and Monitoring Board (DSMB) recommended halting the enrollment of participants randomized to receive either tecovirimat or a placebo. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), accepted this recommendation as the study sponsor. Additionally, due to the absence of an efficacy signal, NIAID decided to close enrollment in an open-label study arm designed for participants with or at high risk of severe disease, which was not intended to evaluate the drug’s effectiveness.

Advancing Mpox Treatment Research

“The initial STOMP findings provide valuable insight to inform clade II mpox medical countermeasures and underscore the critical importance of conducting well-designed randomized clinical trials during infectious disease outbreaks,” said NIAID Director Jeanne Marrazzo, M.D., M.P.H. “Before 2022, no treatment candidate had been studied in people with mpox, and this trial is a critical step in our systematic evaluation of existing antivirals like tecovirimat while pursuing novel antivirals and antibody-based mpox therapeutics.”

Clades I and II: Geographic and Global Impact

Mpox is caused by a virus that spreads mainly through close contact. Two types of the virus have been identified, referred to as clades I and II, historically present in Central and West Africa, respectively. A clade II subtype virus caused a global mpox outbreak in 2022 and the virus continues to circulate at low levels. In 2024, a clade I outbreak in Central and East African countries was declared a public health emergency of international concern by the World Health Organization. Travel-related cases of clade I mpox have been reported internationally and the first reported case in the United States was diagnosed on November 15. In the United States, the risk of clade I mpox to the public remains low. People with significantly compromised immune systems or certain preexisting skin conditions, children, and individuals who are pregnant have an elevated risk of developing severe mpox. Tecovirimat, also known as TPOXX, was initially approved by the Food and Drug Administration (FDA) to treat smallpox—a virus closely related to, but far more serious than, the virus that causes mpox—but the drug’s safety and efficacy as an mpox treatment have not been established prior to this year.

Study Design

The STOMP study began in September 2022 as part of the U.S. whole-of-government response to the clade II mpox outbreak. The randomized international efficacy study enrolled participants who had been ill with mpox for less than 14 days in Argentina, Brazil, Japan, Mexico, Peru, Thailand and the United States, including Puerto Rico. Participants were randomized at a two-to-one ratio to receive tecovirimat or a placebo. Randomized participants and investigators were blinded, meaning they did not know who received tecovirimat or placebo. Children, pregnant people, and other participants with severe disease, certain skin conditions, or substantially suppressed immune systems were assigned to an open-label study arm, meaning they all received tecovirimat instead of being randomized. The STOMP study assessed all participants’ safety and, in randomized arms, evaluated whether a 14-day course of tecovirimat reduced the time to clinical resolution of visible mpox lesions and improved other outcome measures like pain, compared to a placebo.

No Efficacy in Lesion Resolution or Pain Relief

A planned interim analysis at 75% of the study’s target enrollment showed there was no difference in the time to lesion resolution between participants treated with tecovirimat compared with those who received a placebo. Pain decreased similarly between participants treated with tecovirimat and those who received a placebo. At the DSMB’s request, an additional assessment was performed and showed that there was a less than 1% chance that the study would show tecovirimat to be effective if it were to complete enrollment and follow-up, based on the study design and available data. At the time of analysis, reported adverse events were low and comparable between tecovirimat and placebo. By design, the open-label study arm did not assign participants to receive a placebo, so STOMP will not draw conclusions about the efficacy of tecovirimat in participants with, or at elevated risk for, severe clade II mpox.

Ongoing Data Analysis

Further analyses of the study data are ongoing. Study participants are being notified of the findings and study clinicians will make individual clinical care plans with participants based on their disease severity and symptoms. The Centers for Disease Control and Prevention (CDC) holds an expanded access investigational new drug (EA-IND) protocol for mpox treatment outside of research settings. Eligible persons include those with severe immunocompromise, including people with advanced HIV, for whom the role of tecovirimat treatment has not been fully established through a clinical trial. Information on the tecovirimat EA-IND is on the CDC Web site.

Public Health Collaboration in Action

“STOMP was a banner study for its speed of startup, inclusiveness, and collaboration across governments and public health authorities” said study chair Timothy Wilkin, M.D., M.P.H., chief of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego. “This study may serve as a model for outbreak response, delivering essential scientific evidence while also enabling equitable treatment access.”

The STOMP findings are consistent with results reported earlier this year from a NIAID-cosponsored randomized controlled trial of tecovirimat among children and adults with clade I mpox in the Democratic Republic of the Congo.

Reference:

1. Assessment of the Efficacy and Safety of Tecovirimat in Patients with Monkeypox Virus Disease (UNITY) – (https://clinicaltrials.gov/study/NCT05597735)

Source-Eurekalert