Safety and Preliminary Efficacy of Dengue Monoclonal Antibody in Adult Patients: A Randomized Clinical Trial.

Importance: Dengue outbreaks are increasing in frequency and intensity. In the absence of any specific treatment, a pan-serotype recombinant monoclonal antibody (Dengue-mAb) was tested in adult patients with dengue as a therapeutic option. Objective: To assess the safety and effect of a single dose of Dengue-mAb on dengue viremia at different dose levels among patients with dengue. Design, Setting, and Participants: A phase 2, single-blind, randomized, placebo-controlled clinical trial was conducted from September 19, 2021, to May 13, 2023, at 12 hospitals in India. Study participants were aged 18 to 60 years with dengue and a history of fever onset within 48 hours. Key exclusion criteria were severe dengue, hemoglobin less than 10 g/dL, absolute neutrophil count less than 500/mm3, total leukocyte count less than 1500/mm3, platelet count less than 50 000/mm3, and any other clinically significant disorders. Data were analyzed from January 11, 2024, to March 26, 2024. Interventions: Participants were randomly allocated 1:1:1:1:1 using an interactive web response system to receive 1 of 4 dose levels of Dengue-mAb (3, 5, 7, or 9 mg/kg) or placebo by slow intravenous infusion. Main Outcomes and Measures: Primary outcomes were reduction in viremia at 24 hours and causally related serious adverse events (SAEs). Secondary outcomes were RNAemia, fever, and hematologic and pharmacokinetic parameters. Findings: A total of 250 participants were randomized, with 50 participants in each group. The overall median age was 30 years (IQR, 24-37 years), and 180 participants (72.3%) were male. There were no causally related SAEs. The adjusted mean (SE) viral log reduction at 24 hours was significantly higher with Dengue-mAb-from 1.93 (0.23) with 3 mg/kg (P = .04) to 2.35 (0.27) with 9 mg/kg (P = .003)-compared with placebo (1.29 [0.22]), using a mixed model for repeated measures. Participants with detectable viremia (n = 32) at baseline were negative for dengue virus by 8 hours when treated with a 5- to 9-mg/kg dose of Dengue-mAb compared with 72 hours with placebo. Median time to fever clearance was 3.5 (95% CI, 1.0-24.0) hours (hazard ratio [HR], 2.6 [95% CI, 1.0-6.4]) with Dengue-mAb 5 mg/kg (n = 14) and 2.0 (95% CI, 0.5-6.0) hours (HR, 2.8 [95% CI, 1.2-6.8]) with Dengue-mAb 7 mg/kg (n = 14), compared with 26.8 (95% CI, 1.0-50.5) hours with placebo (n = 12). At 24 hours, between 13 of 14 participants (92.9%; 95% CI, 66.1%-99.8%) with Dengue-mAb (3 mg/kg), 14 of 14 participants (100.0%; 95% CI, 76.8%-100.0%) with Dengue-mAb (5 mg/kg and 7 mg/kg), and 16 of 17 participants (94.1%; 95% CI 71.3%-99.9%) with Dengue-mAb (9 mg/kg); and 7 of 12 participants (58.3%; 95% CI, 27.7%-84.8%) with placebo had fever clearance. Conclusions and Relevance: In this randomized clinical trial, Dengue-mAb was safe and well tolerated. Dengue-mAb rapidly reduced dengue viremia and fever at doses of 5 mg/kg and 7 mg/kg, making this the first therapeutic against wild-type dengue virus to show preliminary efficacy in humans. Trial Registration: Clinical Trial Registry-India Identifier: CTRI/2021/07/035290.