Study of Tecovirimat for Human Monkeypox Virus (STOMP)

• ClinicalTrials.gov Identifier: NCT05534984
• Recruitment Status: Recruiting
• First Posted: September 10, 2022
• Last Update Posted: April 18, 2024
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: SIGA Technologies
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: September 8, 2022
• First Posted Date: September 10, 2022
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: September 12, 2022
• Estimated Primary Completion Date: May 30, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 8, 2022): 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 [ Time Frame: Up to day 29 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 8, 2022)

• Pain assessed by 11-point numerical rating scale for pain [ Time Frame: Through day 29 ]
• Time to development of severe HMPXV in those without severe HMPXV at baseline [ Time Frame: Through day 57 ]
• Level of HMPXV in blood [ Time Frame: Through day 57 ]
• Level of HMPXV in skin lesions [ Time Frame: Through day 57 ]
• Level of HMPXV in oropharynx [ Time Frame: Through day 57 ]
• Level of HMPXV in rectum [ Time Frame: Through day 57 ]
• Level of HMPXV in genital secretions [ Time Frame: Through day 57 ]
• Time to complete lesion healing defined as all lesions being re-epithelialized [ Time Frame: Up to day 29 ]
• Participant-reported adherence [ Time Frame: Through day 15 ]
• Participant-reported quality-of-life as measured by EQ-5D-5L [ Time Frame: Through day 29 ]
• Occurrence of Grade 3 or greater adverse event [ Time Frame: Through day 57 ]
• All-cause mortality [ Time Frame: Through day 57 ]
• Tecovirimat concentrations in blood in children less than 18 years of age [ Time Frame: Through day 15 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Tecovirimat for Human Monkeypox Virus
• Official Title: A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease
• Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Monkeypox
• MPOX

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
• Drug: 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
• Drug: 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

Study Arms

• Experimental: Arm A
  Intervention: Drug: Tecovirimat Oral Capsule
• Placebo Comparator: Arm B
  Intervention: Drug: Placebo
• Experimental: Arm C
  Intervention: Drug: Tecovirimat Oral Capsule (Open Label)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 8, 2022): 530
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: May 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: ACTG Clinicaltrials.gov Coordinator; Please email at:; ACTGCT.gov@fstrf.org

• Listed Location Countries: Argentina, Brazil, Japan, Mexico, Peru, Puerto Rico, South Africa, Thailand, United States

Administrative Information

• NCT Number: NCT05534984
• Other Study ID Numbers: A5418; 38982 ( Other Identifier: DAIDS-ES ID )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie results in the publication after deidentification
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH

Access Criteria

With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.

For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.

By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data

• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: SIGA Technologies

Investigators

• Study Chair: Timothy Wilkin, MD, MPH; Cornell

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: April 2024