Survodutide for the Treatment of Obesity Disease in Japanese Participants: Rationale, Design and Baseline Characteristics of the Phase 3 SYNCHRONIZE-JP Trial.

AIMS: There is an unmet need for effective pharmacotherapy for obesity disease management in Japan. Survodutide is a novel glucagon receptor/glucagon-like peptide-1 receptor (GLP-1R) dual agonist with the potential to induce greater weight reductions than GLP-1R mono-agonists. We report the design and baseline participant characteristics of the SYNCHRONIZE-JP trial evaluating survodutide in Japanese adults with obesity disease (ClinicalTrials.gov: NCT06176365). MATERIALS AND METHODS: SYNCHRONIZE-JP is a 76-week, randomised, double-blind, parallel-group, multi-centre, phase 3 clinical trial. Eligible participants were aged ≥ 18 years, with BMI ≥ 35 kg/m with ≥ 1 obesity complication or BMI ≥ 27 kg/m with ≥ 2 obesity complications, ≥ 1 self-reported unsuccessful dietary effort to lose body weight and ≥ 1 obesity complication required to be type 2 diabetes (T2D; capped at 30% enrolment), hypertension or dyslipidaemia. Participants were randomised 1:1:1 to receive once-weekly survodutide 3.6 or 6.0 mg, or placebo, accompanied by a reduced-calorie diet and increased physical activity. The primary endpoints are percentage change in body weight and achievement of body weight reduction ≥ 5% from baseline to Week 76. A subset of participants will be assessed for additional endpoints of liver fat content and body composition. RESULTS: Of 274 enrolled participants, 24.1% had T2D. The mean age was 53.1 years; 47.8% were female, and mean BMI was 33.2 kg/m. The most frequent complications were dyslipidaemia (81.4%), hypertension (72.6%), hyperuricaemia (30.3%) and metabolic dysfunction-associated steatotic liver disease (26.6%). CONCLUSIONS: The results of SYNCHRONIZE-JP will provide Japan-specific efficacy, safety and tolerability data for survodutide and inform its potential role in the management of obesity disease.