A5418

ACTG 5418 is a phase 3, randomized, placebo-controlled, double-blind trial of tecovirimat for the treatment of human monkeypox virus (HMPXV) disease. The study will also include a cohort of people who will receive open-label tecovirimat including people with protocol-defined severe HMPXV, pregnant and breastfeeding women, individuals less than 18 years of age, individuals on potent inducing concomitant medications, people with severe immune suppression or skin conditions placing them at higher risk for severe disease.

Participants with symptomatic HMPXV who do not meet criteria for the open-label cohort will be randomized in a 2:1 ratio to tecovirimat or matching placebo for 14 days. All participants will be followed through a combination of virtual assessments, in-person visits, and daily self-reports for resolution of clinical disease, specimen collection to assess viral clearance, and participant reported outcomes through day 57.

Participants who progress to severe disease post-randomization will be offered open-label tecovirimat. Participants who report severe pain from HMPXV will be offered open-label tecovirimat as early as 5 days post-randomization.

The primary endpoint is the time to clinical resolution defined as all skin lesions being scabbed, desquamated, or healed, and all visible mucosal lesions being healed.