Study of Tecovirimat for Human Mpox Virus

NCT05534984 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: A541838982
• Study Type: interventional
• Target: 719
• Locations: 6 countries
• Sites: 54

Brief Summary

The purpose of this study was to see if tecovirimat is safe and successful at treating mpox. The main questions were whether tecovirimat reduced time to lesion resolution and pain compared to placebo (no treatment).

Conditions

MPOX

Keywords

HMPXV

Outcome Measures

Primary Outcomes (1)

• Cumulative Proportion With Clinical Resolution by Day 29

  Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative incidence of clinical resolution was estimated using the Aalen-Johansen estimator. The treatment effect, i.e., the subdistribution hazard ratio of tecovirimat relative to placebo, was estimated using the Fine and Gray subdistribution proportional hazards model. All-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.

  From study entry through 28 days of follow-up (i.e., Day 29)

Secondary Outcomes (19)

• Mean Time-weighted Average of Pain Intensity Difference Over 5 Days of Treatment

  Through 5 days of treatment (i.e., Treatment Day 6)

• Mean Time-weighted Average of Pain Intensity Difference Over 14 Days of Treatment

  Through 14 days of treatment (i.e., Treatment Day 15)

• Number of Participants Who Developed Severe HMPXV Disease

  From study entry through 56 days of follow-up (i.e., Day 57)

• Number of Participants With HMPXV DNA Below Limit of Detection in Skin Lesions

  Baseline, Days 8, 15, 22, 29, and 57

• Number of Participants With HMPXV DNA Below Limit of Detection in Oropharynx

  Baseline, Days 8, 15, 22, 29, and 57

Study Arms (3)

Tecovirimat (Arm A)

EXPERIMENTAL

Participants randomized to tecovirimat.

Drug: Tecovirimat Oral Capsule

Placebo (Arm B)

PLACEBO COMPARATOR

Participants randomized to placebo.

Drug: Placebo for Tecovirimat

Open-Label Tecovirimat (Arm C)

EXPERIMENTAL

Participants assigned to open-label tecovirimat.

Drug: Tecovirimat Oral Capsule (Open Label)

Interventions

Tecovirimat Oral Capsule DRUG

* Participants weighing 25 kg to less than 40 kg - Tecovirimat 400 mg every 12 hours for 14 days * Participants weighing 40 kg to less than 120 kg - Tecovirimat 600 mg every 12 hours for 14 days * Participants weighing 120 kg and over - Tecovirimat 600 mg every 8 hours for 14 days

Tecovirimat (Arm A)

Placebo for Tecovirimat DRUG

* Participants weighing 25 kg to less than 40 kg - Placebo for Tecovirimat 400 mg every 12 hours for 14 days * Participants weighing 40 kg to less than 120 kg - Placebo for Tecovirimat 600 mg every 12 hours for 14 days * Participants weighing 120 kg and over - Placebo for Tecovirimat 600 mg every 8 hours for 14 days

Placebo (Arm B)

Tecovirimat Oral Capsule (Open Label) DRUG

* Participants weighing \<3 kg - Tecovirimat 33.3 mg every 12 hours for 14 days * Participants weighing 3 kg to less than 6 kg- Tecovirimat 50 mg every 12 hours for 14 days * Participants weighing 6 kg to less than 13 kg - Tecovirimat 100 mg every 12 hours for 14 days * Participants weighing 13 kg to less than 25 kg - Tecovirimat 200 mg every 12 hours for 14 days * Participants weighing 25 kg to less than 40 kg - Tecovirimat 400 mg every 12 hours for 14 days * Participants weighing 40 kg to less than 120 kg - Tecovirimat 600 mg every 12 hours for 14 days * Participants weighing 120 kg and over - Tecovirimat 600 mg every 8 hours for 14 days

Open-Label Tecovirimat (Arm C)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Laboratory-confirmed or presumptive human mpox virus (HMPXV) infection.
• HMPXV illness of \<14 days duration immediately prior to study entry.
• At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.
• Non-pregnant people of reproductive potential must agree to use at least one effective means of contraception when engaging in sexual activities that can result in pregnancy, from the time of enrollment through the end of study participation.
• Ability to provide informed consent (for those above the legal age of consent and those providing consent for minors) and assent (for those who have reached the age of assent, but not the legal age of consent), as allowed by local ethics committees.
• For participants to be enrolled/followed remotely, ability and willingness to participate in remote telehealth assessments (i.e., video visits).
• \. Age ≥18 years at the time of study entry.
• Participants who meet the above entry criteria who also meet any of the following criteria will be registered to Arm C.
• Age \<18 years at the time of study entry.
• Those with severe HMPXV disease defined as having one or more of the following conditions:
• Suspected or confirmed ocular involvement
• Facial lesions on the malar, nose, or eyelid region
• Confluent facial lesions
• Hospitalization due to HMPXV infection or its complications
• Lesions that require surgical intervention including debridement, urinary catheterization or sigmoidoscopy, or lesions extending below the dermis.

You may not qualify if:

• Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.
• Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who were stable on long-acting intramuscular cabotegravir/rilpivirine were allowed to enroll.
• Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.
• Participants who require intravenous dosing of tecovirimat.

Sponsors & Collaborators

• SIGA Technologies: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (54)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Los Angeles LGBT Center CRS

Los Angeles, California, 90028, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

University of California, Davis CRS

Sacramento, California, 95817, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

Location

Harbor University of California Los Angeles Center

Torrance, California, 90502, United States

Location

University of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Denver Public Health CRS

Denver, Colorado, 80204, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

University of Miami / Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Univ. of South Florida (USF) College of Medicine A

Tampa, Florida, 33606, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

Location

Rush University Cook County Hospital Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital CRS

Detroit, Michigan, 48202, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School Clinical Research Center

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Mount Sinai West Samuels CRS

New York, New York, 10019, United States

Location

Harlem Prevention Center

New York, New York, 10027, United States

Location

Columbia Physicians & Surgeons (P&S) CRS

New York, New York, 10032, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

Bronx-Lebanon Hospital Center NICHD CRS

New York, New York, 10457, United States

Location

Infectious Disease Clinical and Translational Research

New York, New York, 11029, United States

Location

University of Rochester Adult HIV Therapeutic

Rochester, New York, 14642, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794, United States

Location

Duke University Medical Center CRS

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Medical Center CRS

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University CTU

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital ATN CRS

Memphis, Tennessee, 38105, United States

Location

North Texas Infectious Disease Consultants

Dallas, Texas, 75246, United States

Location

UT Southwestern Infectious Disease Research Unit

Dallas, Texas, 75390, United States

Location

Houston AIDS Research Team (HART) CRS

Houston, Texas, 77030, United States

Location

University of Washington Positive Research

Seattle, Washington, 98104, United States

Location

Fundacion Huesped CRS

Buenos Aires, Argentina

Location

Centro de Pesquisas Clínicas IC-HCFMUSP CRS

São Paulo, Brazil

Location

Nutricion Mexico CRS

Mexico City, Mexico

Location

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) CRS

Callao, Peru

Location

Barranco CRS

Lima, Peru

Location

San Miguel CRS

Lima, Peru

Location

Socios En Salud Sucursal Peru

Lima, Peru

Location

Via Libre CRS

Lima, Peru

Location

Thai Red Cross AIDS Research Centre

Bangkok, Thailand

Location

Vaccine Trial Centre, Mahidol University CRS

Bangkok, Thailand

Location

Related Publications (2)

• Zucker J, Fischer WA 2nd, Zheng L, McCarthy C, Saha PT, Javan AC, Greninger A, Hamill MM, Leslie K, Brooks KM, Berardi J, Smith D, Hosey L, Aldrovandi G, Ferbas K, Day C, Bender Ignacio RA, Bolan R, Glesby MJ, Landovitz RJ, Luetkemeyer AF, Sierra Madero J, Gandhi RT, Nachman S, Eron J, Currier JS, Wilkin T; STOMP/A5418 Investigators. Tecovirimat for the Treatment of Mpox. N Engl J Med. 2026 Feb 26;394(9):884-895. doi: 10.1056/NEJMoa2506495.

  PMID: 41740032 DERIVED

• Chenchula S, Atal S, Ghanta MK, Uppugunduri CR, Karunakaran S, Amerneni KC, Sarma P, Prakash S, Amerneni LS, Padmavathi R, Anitha K, Sri Varshini T, Vishnu Vardhan K, Kaore S, Sadasivam B. Emerging variants of Mpox virus and tecovirimat resistance: Genomic insights and implications for treatment strategies. Virology. 2025 Jul;608:110532. doi: 10.1016/j.virol.2025.110532. Epub 2025 Apr 12.

  PMID: 40245474 DERIVED

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
• DAIDS EAE Manual, Version 2.0

MeSH Terms

Conditions

Mpox, Monkeypox

Interventions

tecovirimat

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Limitations and Caveats

Enrollment to the trial was stopped early due to statistical futility based on a recommendation from an independent DSMB at the second interim efficacy review.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Timothy Wilkin, MD, MPH

  Cornell

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 10, 2022
• Study Start: September 8, 2022
• Primary Completion: October 23, 2024
• Study Completion: February 22, 2025
• Last Updated: February 10, 2026
• Results First Posted: February 10, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. For what types of analyses? To achieve aims in the proposal approved by the ACTG. By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data

Locations

TH (2); AR (1); BR (1); PE (5); US (44); ME (1)