Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo

Abstract

Background: Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking.

Methods: We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed.

Results: From October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization - 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P = 0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively.

Conclusions: Tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.).

Figure 1a.

Cumulative incidence of lesion resolution (ITT population). Shown are Kaplan-Meier estimates of the cumulative incidence of lesion resolution. Panels A, B, and C shows the estimates in the overall population, those enrolled within 7 days of symptom onset, and those enrolled more than 7 days after symptom onset, respectively.

Figure 1a.

Cumulative incidence of lesion resolution (ITT population). Shown are Kaplan-Meier estimates of the cumulative incidence of lesion resolution. Panels A, B, and C shows the estimates in the overall population, those enrolled within 7 days of symptom onset, and those enrolled more than 7 days after symptom onset, respectively.

Figure 1a.

Cumulative incidence of lesion resolution (ITT population). Shown are Kaplan-Meier estimates of the cumulative incidence of lesion resolution. Panels A, B, and C shows the estimates in the overall population, those enrolled within 7 days of symptom onset, and those enrolled more than 7 days after symptom onset, respectively.

Figure 2.

Longitudinal PCR-negativity results through 14 days by treatment arm (ITT) and onset of symptoms (overall, ≤7 days, >7 days) for blood, oropharynx, and skin lesion samples Patients are presented according to their randomized treatment group, and patients with a baseline PCR−Positive or PCR−Negative result are included. Last−observation−carried−forward logic was applied to valid MPXV PCR results from baseline to 14 days post−randomization. Patients who achieve lesion resolution (Res) are not expected to have further skin lesion PCR results, so patients who reach lesion resolution on or before the given timepoint are assumed to be PCR negative if no valid PCR data exist. Data extraction: 2024−08−21; Last run: 2024−09−18 17:09:46 EDT; Pathname: …/f_PCR_lineplot_overtime_simple_bystrata

Figure 3.

Days to lesion resolution by subgroup, with interaction models and interaction-test p-values (ITT population) Symptom duration sensitivity analyses with three categories was post hoc. The overall HR was estimated using a Cox proportional hazards model stratified by days of symptoms prior to randomization (<=7 and >7). Other HR estimates were derived from Cox models with treatment by covariate interaction terms. Median days to resolution was estimated using the Kaplan-Meier procedure.