Study of Tecovirimat for Human Monkeypox Virus

Overview

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.

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.