Background
Mpox has caused two international public health emergencies; no therapies have established efficacy. ACTG A5418/STOMP is a phase 3 randomized placebo-controlled double-blind trial evaluating the efficacy of tecovirimat, an antiviral with animal data supporting its use for orthopox infections.
Methods
Participants ≥18 years with symptomatic laboratory-confirmed or presumptive mpox <14 days were randomized 2:1 to oral tecovirimat 600mg twice daily or placebo for 14 days. Participants with or at risk for severe disease, pregnant women and children were enrolled in an open-label arm. The primary outcome was time to clinical resolution (all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed) by Day 29. The secondary outcome included mean pain score reduction over 5 days, and longitudinal mpox DNA changes from a representative skin lesion for those enrolled in person. In November 2024, the Data and Safety Monitoring Board recommended stopping randomization based on a futility analysis.
Results
Of 412 eligible participants randomized to tecovirimat (275) or placebo (137) at 50 sites in 7 countries, 24% were enrolled remotely, 98% were male, 97% were cisgender, and median age was 34 years; 53% white, 11% black, 45% Hispanic; 33% living with HIV; 22% had received ≥1 dose of mpox vaccine. At entry median symptom duration was 8 days (IQR 5,10), median lesion number was 9 (IQR 4, 19; max 242), 33% had severe pain (7-10 on 11-point scale); 68 (17%) did not have mpox diagnosed and were excluded. By Day 29, the estimated cumulative incidence of clinical resolution was 83% and 84%, respectively (instantaneous risk ratio 0.98, nominal 98.1% CI: 0.74-1.31; p=0.89) (Figure). Receipt of open-label tecovirimat due to disease progression or persistent severe pain was the same (7% in each arm). Adverse events were similar (11% vs. 9%). Among those with severe pain at baseline (a pre-specified analysis), mean [sd] pain score reduction was similar for tecovirimat (3.2 [2.1]) and placebo (3.1 [2.0]). More participants in tecovirimat arm had undetectable mpox DNA at Day 8 (48%) compared to placebo (33%) but no meaningful difference at Day 15 (83% and 78% respectively).
Conclusions
Tecovirimat did not reduce clinical resolution of mpox lesions or improve pain control among adults with clade II mpox. These results do not support the continued use of tecovirimat monotherapy for mpox.