Efsubaglutide alfa in adults with overweight or obesity: Protocol for a seamless, adaptive phase 2b/3 randomized,...

To describe the design and rationale of LIGHT 2, a seamless, adaptive phase 2b/3 trial evaluating the efficacy and safety of efsubaglutide alfa for chronic weight management in adults with overweight or obesity.

LIGHT 2 is a multicentre, randomized, double-blind, placebo-controlled study in which eligible participants are assigned to efsubaglutide alfa dose regimens or matched placebo. Efsubaglutide alfa is administered with a prespecified dose-escalation scheme to target maintenance doses delivered once weekly or once every 2 weeks. The seamless, adaptive framework enables interim evaluation to support regimen selection and progression to the confirmatory phase under a single protocol with maintained blinding and centralized oversight. An independent data monitoring committee reviews interim safety and adaptive decisions per a prespecified charter.

The primary efficacy endpoint is percentage change in body weight. Key secondary endpoints include categorical weight-loss thresholds, changes in anthropometric and cardiometabolic measures, and comprehensive safety and tolerability assessments; an imaging substudy will further characterize effects on ectopic fat in a subset of participants.

LIGHT 2 is designed to efficiently identify and confirm an efsubaglutide alfa regimen with clinically meaningful weight-loss efficacy and an acceptable safety profile, while generating evidence relevant to real-world implementation.