Study of Tecovirimat for Human Mpox Virus (STOMP)

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 3

Conditions: MPOX

Treatments: Drug: Tecovirimat Oral Capsule (Open Label); Drug: Placebo for Tecovirimat; Drug: Tecovirimat Oral Capsule

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT05534984

A5418

38982 (Other Identifier)

Details and patient eligibility

About

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).

Full description

This phase 3, randomized, placebo-controlled, double-blind clinical trial evaluated the efficacy of tecovirimat for the treatment of mpox. Participants who had or were at higher risk for severe disease because of their age or medical history, were pregnant or breastfeeding, or were taking medications that could have decreased their exposure to tecovirimat were assigned to receive open-label tecovirimat for 14 days. All other participants were randomized 2:1 to receive either tecovirimat or placebo for 14 days.

Randomized participants who reported severe pain 5 days after randomization (on Day 6) or later or progressed to severe disease stopped blinded study treatment and started a 14-day course of open-label tecovirimat.

Participants self-monitored lesions daily through 28 days (Day 29) or resolution, whichever came first, and completed a daily pain scale and symptom diary. Study visits occurred weekly through 28 days (Day 29) and included safety and skin assessments and specimen collections. A final study visit occurred at 56 days (Day 57) to assess for recrudescence of infection (development of new lesions after initial resolution of disease).

Version 3 of the protocol gave participants the option to enroll and complete study visits remotely. Participants did not provide specimens at remote visits.

On November 26, 2024, the Data and Safety Monitoring Board (DSMB) recommended that the study close due to statistical futility. The study team and sponsor agreed with the DSMB's recommendation and the study closed to accrual on November 27, 2024. The primary analysis report forming the basis of the primary manuscript used data from follow-up visits occurring through October 23, 2024, the data cutoff for the November 2024 DSMB review (the primary completion date). Outcome measures submitted to clinicaltrials.gov were also based on data from follow-up visits occurring through October 23, 2024, and summaries of participant flow, baseline characteristics, and adverse events submitted to clinicaltrials.gov were based on data from follow-up visits occurring through February 22, 2025 (the study completion date).

Enrollment: 719 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

1. Laboratory-confirmed or presumptive human mpox virus (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.
5. 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.
6. For participants to be enrolled/followed remotely, ability and willingness to participate in remote telehealth assessments (i.e., video visits).

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. Age <18 years at the time of study entry.

2. 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.

Those with or without severe disease and with one or more of the following:

• Severe immunosuppression
• Active skin conditions placing the person at higher risk for disseminated infection
• Breastfeeding
• Pregnancy
• Receipt of potent inducers
• Current or planned use of another investigational drug at any point during tecovirimat/placebo dosing that would be predicted to have a significant drug-drug interaction with tecovirimat therapeutics.

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 were stable on long-acting intramuscular cabotegravir/rilpivirine were allowed to 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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719 participants in 3 patient groups, including a placebo group

Tecovirimat (Arm A)

Experimental group

Description:

Participants randomized to tecovirimat.

Treatment:

Drug: Tecovirimat Oral Capsule

Placebo (Arm B)

Placebo Comparator group

Description:

Participants randomized to placebo.

Treatment:

Drug: Placebo for Tecovirimat

Open-Label Tecovirimat (Arm C)

Experimental group

Description:

Participants assigned to open-label tecovirimat.

Treatment:

Drug: Tecovirimat Oral Capsule (Open Label)