Study of Tecovirimat for Human Monkeypox Virus

Monkeypox Clinical Trial

— STOMP  

Official title:

A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05534984
• Other study ID #: A5418
• Secondary ID: 38982
• Status: Recruiting
• Phase: Phase 3
• Start date: September 12, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: ACTG Clinicaltrials.gov Coordinator
• Phone: Please email at:
• Email: ACTGCT.gov[@]fstrf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A5418 is a randomized, placebo-controlled, double-blind study to establish the efficacy of tecovirimat for the treatment of people with laboratory-confirmed or presumptive HMPXV disease.

Description:

Eligible and consented participants for the randomized arms (N=530) will be randomized 2:1 to receive either tecovirimat or placebo; participants with severe disease, significant skin conditions, participants with severe immune suppression will receive open-label tecovirimat. Participants who are pregnant or breastfeeding will receive open-label tecovirimat after discussion of the potential risks and benefits. Participants less than 18 years of age will receive open-label tecovirimat. Participants receiving a potent inducing concomitant medication will receive open-label tecovirimat.

Once enrolled, study drug administration will be for 14 days. Participants who progress to severe HMPXV disease will be seen in person for a confirmation of progression. If severe disease is confirmed, participants will stop blinded study treatment and start a 14-day course of open-label tecovirimat. Participants reporting severe pain 5 days after randomization will stop blinded study treatment and start a 14-day course of open-label tecovirimat.

Participants will self-monitor skin and/or mucosal lesions daily through 29 days or resolution (whichever comes first), complete a daily diary of symptoms and complete a daily numerical rating scale for pain assessment.

Participants will be seen weekly through day 29 for assessment of HMPXV disease, safety assessments, HMPXV sampling similar to that described for entry, and swabbing of new HMPXV lesions.

Participants will be seen at day 57 to assess for possible recrudescence of infection (i.e., new lesions occurring after initial resolution of disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 530
• Est. completion date: September 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria (All participants; Arms A, B, and C):

1. Laboratory-confirmed or presumptive HMPXV infection.

2. HMPXV illness of <14 days duration immediately prior to study entry.

3. At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.

4. 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.

Additional Inclusion Criteria for Arms A and B:

1. Age =18 years at the time of study entry

Additional Inclusion Criteria for Arm C; Participants who meet the above entry criteria who also meet any of the following criteria will be registered to Arm C:

1. Participants age <18 years at the time of study entry

2. Those with severe HMPXV disease

Those with or without severe disease and with one or more of the following will also be enrolled into Arm C:

• Severe immunosuppression

• Skin conditions placing the person at higher risk for disseminated infection

Exclusion Criteria (All participants; Arms A, B, and C):

1. Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.

2. Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who are stable on long-acting intramuscular cabotegravir/rilpivirine may enroll.

3. Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.

4. Participants who require intravenous dosing of tecovirimat.

Related Conditions & MeSH terms

• Monkeypox

Intervention

Drug:
• Tecovirimat Oral Capsule
Drug: Tecovirimat Oral capsules 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
• Placebo
Drug: Placebo Oral capsules 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
• Tecovirimat Oral Capsule (Open Label)
Participants weighing 4 to <6kg and >7 days old - Tecovirimat 50mg every 12 hours for 14 days Participants weighing 2.5 to <4kg and >7 days to <4 weeks old - Tecovirimat 20 mg every 12 hours for 14 days Participants weighing 4 to <6kg and =7 days old - Tecovirimat 50mg every 24 hours for 14 days Participants weighing 2.5 to <4 kg and =7 days old - Tecovirimat 20mg every 24 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 (2 capsules) 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

Locations

Country	Name	City	State
Argentina	Fundacion Huesped CRS	Buenos Aires
Brazil	Hospital Nossa Senhora da Conceicao CRS	Porto Alegre
Brazil	Centro de Pesquisas Clínicas IC-HCFMUSP CRS	São Paulo
Brazil	Centro de Referencia e Treinamento DST/AIDS CRS	São Paulo
Japan	National Center for Global Health and Medicine	Tokyo
Mexico	Nutricion Mexico CRS	Mexico City
Peru	Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) CRS	Callao
Peru	Barranco CRS	Lima
Peru	San Miguel CRS	Lima
Peru	Socios En Salud Sucursal Peru	Lima
Peru	Via Libre CRS	Lima
Puerto Rico	IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS	San Juan
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit CRS	San Juan
South Africa	Soweto CRS	Johannesburg
South Africa	University of the Witwatersrand Helen Joseph (WITS HJH)	Johannesburg
Thailand	Mahidol University CRS	Bangkok
Thailand	Thai Red Cross AIDS Research Centre	Bangkok
United States	The Ponce de Leon Center CRS	Atlanta	Georgia
United States	University of Colorado Denver NICHD CRS	Aurora	Colorado
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins University CRS	Baltimore	Maryland
United States	Alabama CRS	Birmingham	Alabama
United States	Brigham and Women's Hospital Therapeutics	Boston	Massachusetts
United States	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts
United States	Jacobi Medical Center Bronx NICHD CRS	Bronx	New York
United States	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Rush University Cook County Hospital Chicago NICHD CRS	Chicago	Illinois
United States	Rush University CRS	Chicago	Illinois
United States	Cincinnati CRS	Cincinnati	Ohio
United States	Case Western Reserve University CTU	Cleveland	Ohio
United States	Ohio State University CRS	Columbus	Ohio
United States	North Texas Infectious Disease Consultants	Dallas	Texas
United States	Trinity Health and Wellness Center CRS	Dallas	Texas
United States	UT Southwestern Infectious Disease Research Unit	Dallas	Texas
United States	Denver Public Health CRS	Denver	Colorado
United States	Henry Ford Hospital CRS	Detroit	Michigan
United States	Duke University Medical Center CRS	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine / Texas Children's Hospital NICHD CRS	Houston	Texas
United States	Houston AIDS Research Team (HART) CRS	Houston	Texas
United States	University of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	David Geffen School of Medicine at UCLA NICHD CRS	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles LGBT Center CRS	Los Angeles	California
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	St. Jude Children's Research Hospital ATN CRS	Memphis	Tennessee
United States	University of Miami / Jackson Memorial Hospital	Miami	Florida
United States	University of Miami/Pediatric Perinatal HIV NICHD CRS	Miami	Florida
United States	Vanderbilt Therapeutics CRS	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Bronx-Lebanon Hospital Center NICHD CRS	New York	New York
United States	Columbia Physicians & Surgeons (P&S) CRS	New York	New York
United States	Harlem Prevention Center	New York	New York
United States	Infectious Disease Clinical and Translational Research	New York	New York
United States	Mount Sinai West Samuels CRS	New York	New York
United States	Weill Cornell Chelsea CRS	New York	New York
United States	Weill Cornell Uptown CRS	New York	New York
United States	New Jersey Medical School Clinical Research Center	Newark	New Jersey
United States	Easy Bay AIDS Center CRS City: Oakland	Oakland	California
United States	University of Nebraska Medical Center (Specialty Care Center)	Omaha	Nebraska
United States	Penn Therapeutics CRS	Philadelphia	Pennsylvania
United States	University of Pittsburgh CRS	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University Division of Infectious Diseases	Richmond	Virginia
United States	University of Rochester Adult HIV Therapeutic	Rochester	New York
United States	University of California, Davis CRS	Sacramento	California
United States	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri
United States	University of Texas, San Antonio	San Antonio	Texas
United States	UCSD Antiviral Research Center CRS	San Diego	California
United States	University of California, San Francisco HIV/AIDS CRS	San Francisco	California
United States	University of Washington Positive Research	Seattle	Washington
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	Univ. of South Florida (USF) College of Medicine A	Tampa	Florida
United States	Harbor University of California Los Angeles Center	Torrance	California
United States	Wake Forest Baptist Medical Center CRS	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	SIGA Technologies

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Japan,  Mexico,  Peru,  Puerto Rico,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to clinical resolution, defined as the first day on which all skin lesions are scabbed, desquamated or healed, and visible mucosal lesions are healed		Up to day 29
Secondary	Pain assessed by 11-point numerical rating scale for pain		Through day 29
Secondary	Time to development of severe HMPXV in those without severe HMPXV at baseline		Through day 57
Secondary	Level of HMPXV in blood		Through day 57
Secondary	Level of HMPXV in skin lesions		Through day 57
Secondary	Level of HMPXV in oropharynx		Through day 57
Secondary	Level of HMPXV in rectum		Through day 57
Secondary	Level of HMPXV in genital secretions		Through day 57
Secondary	Time to complete lesion healing defined as all lesions being re-epithelialized		Up to day 29
Secondary	Participant-reported adherence		Through day 15
Secondary	Participant-reported quality-of-life as measured by EQ-5D-5L		Through day 29
Secondary	Occurrence of Grade 3 or greater adverse event		Through day 57
Secondary	All-cause mortality		Through day 57
Secondary	Tecovirimat concentrations in blood in children less than 18 years of age		Through day 15