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Purpose

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.

Condition

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A
  • 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 Comparator
Arm B
  • 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
Experimental
Arm C
  • 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

Recruiting Locations

Alabama CRS
Birmingham, Alabama 35294
Contact:
Sonya Heath, IoR
205-996-2373
slheath@uabmc.edu

More Details

Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.