Efficacy and safety of a 3-day once-daily regimen of oral nafithromycin in comparison to oral moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults: a phase III, randomized, double-blind controlled trial.

BACKGROUND

Nafithromycin, a novel macrolide belonging to the lactone ketolide subclass, exhibits excellent in vitro potency against pathogens causing community-acquired bacterial pneumonia (CABP), in conjunction with high and sustained pulmonary concentrations allowing for once-daily dosing. We aimed to compare efficacy and safety of nafithromycin with moxifloxacin for treatment of CABP.

METHODS

This was a phase III, randomized, double-blind, non-inferiority study in adults with CABP (PORT risk class II, III, IV), conducted at 31 sites across India. Patients were randomized (1:1) via block randomisation using interactive voice/web response system to receive oral nafithromycin 800 mg q24h for 3 days or oral moxifloxacin 400 mg q24h for 7 days. The primary efficacy endpoint was the proportion of patients with early clinical response (ECR) at Day 4 in the modified-intent-to-treat population (MITT). Favourable ECR was defined as alive and ≥1 level improvement in ≥2 CABP symptoms compared to baseline and without worsening of other CABP symptoms. A non-inferiority margin of 12.5% was utilised. This trial is registered with Clinical Trial Registry-India (CTRI/2019/11/021964).

FINDINGS: Between February 2021 and June 2023, 488 patients were enrolled with 244 randomized to each treatment. MITT population included 477 patients with 40% belonging to PORT risk class III/IV. Demography and baseline characteristics were comparable between groups. ECR was observed in 91.3% (220/241) of patients in nafithromycin group and 89.0% (210/236) of patients in moxifloxacin group of the MITT population [difference, 2.3%; 95% CI (-3.1, 7.8)] establishing statistical non-inferiority between treatments. Most common treatment-emergent adverse events reported (≥2% patients in any treatment group) were abdominal pain, diarrhoea, headache and nausea, which were all mild in severity.

INTERPRETATION: A 3-day regimen of oral nafithromycin was non-inferior to a 7-day regimen of oral moxifloxacin for the treatment of CABP.

FUNDING: Co-funded by Wockhardt and BIRAC, Department of Biotechnology, Government of India.