A study evaluating SIR4156 together with semaglutide to reduce body fat in adults with obesity

INTERVENTION: Participants in the intervention arm will receive SIR4156 oral tablets administered twice daily in combination with semaglutide administered as a once‐weekly subcutaneous injection for 24 weeks. Participants will receive either 100 mg or 200 mg SIR4156 according to the protocol‐defined randomised treatment assignment. Semaglutide dosing will be escalated according to the approved product schedule: 0.25 mg once weekly for Weeks 1–4, 0.5 mg once weekly for Weeks 5–8, 1.0 mg once weekly for Weeks 9–12, 1.7 mg once weekly for Weeks 13–16, and 2.4 mg once weekly from Week 17 onwards as the maintenance dose, as tolerated. Semaglutide injections will be self‐administered by participants following training provided by the study team. Adherence to study treatment will be monitored throughout the study using participant dosing diaries, study drug accountability records, and reconciliation of returned study medication at each study visit. Participants will receive instructions on study treatment administration and diary completion, with compliance reviewed by site staff at scheduled visits. CONDITION: Metabolic and Endocrine ‐ Metabolic disorders Obesity; ; Obesity PRIMARY OUTCOME: Percent change from baseline in total body fat mass[Dual‐energy X‐ray absorptiometry (DXA) Baseline and Week 24 post‐baseline] INCLUSION CRITERIA: Adults aged 18 to 75 years with obesity defined as body mass inde Xgreater than or equal to 30 kilograms per square meter, with stable body weight prior to screening, and able to comply with study procedures. SECONDARY OUTCOME: Pharmacodynamic Effects[Pharmacodynamic effects will be evaluated using protocol‐defined blood‐based biomarkers, including markers of metabolic and inflammatory activity, to assess the biological activity of SIR4156 and treatment‐related pharmacodynamic responses throughout the study. Week 24 (Baseline of the Maintenance Phase), Week 32, Week 40, Week 48 (End of Treatment), and Early Termination (if applicable).] Pharmacokinetics of SIR4156[Pharmacokinetic assessments will evaluate plasma concentrations of SIR4156 in blood samples collected at protocol‐defined study visits. Standard pharmacokinetic parameters, including measures of systemic exposure and drug disposition (e.g. AUC, Cmax, Tma Xand terminal elimination half‐life [t½]), will be derived, as appropriate. Pharmacokinetic assessments will be performed at Baseline (Day 1), Weeks 4, 8, 16 and 24, with an additional assessment at Early Termination, if applicable.] Safety[Safety assessments: Safety will be assessed through monitoring of adverse events (AEs) and serious adverse events (SAEs), clinical laboratory assessments, physical examinations, vital signs and electrocardiograms (ECGs), as specified in the study protocol. ; 1. Adverse events: AEs will be assessed by appropriately qualified study personnel in accordance with protocol‐defined criteria, including assessment of severity, seriousness and relationship to study treatment. AEs may be spontaneously reported by participants or identified through routine clinical assessment and non‐leading questioning. This is a routine safety assessment rather than a formal qualitative interview; therefore, a specified interview duration is not applicable. ; 2. Vital signs: Vital signs include body temperature, systolic and diastolic blood pressure, pulse/heart rate, oxygen saturation and respiratory rate. Measurements will be performed using standard appropriately calibrated clinical equipment, including an automated blood pressure monitor and pulse oximeter, in accordance with the protocol. ; 3. ECG: Standard 12‐lead ECG assessments will include heart rate and relevant cardiac conduction and repolarisation parameters, including PR, QRS, QT and QTc intervals, using standard clinical ECG equipment. ; 4. Other safety assessments: Additional safety assessments include protocol‐specified clinical laboratory testing and physical examinations. The assessments will be conducted at Baseline and then every 4 weeks through Week 24.] Tolerability[Tolerability will be assessed through review of adverse events, concomitant medications, study drug accountability, dose modifications, treatment interruptions or discontinuations, and investigator clinical assessments at protocol‐defined study visits. Relevant information will also be collected directly from participants during routine one‐on‐one discussions with study staff at study visits, during which participants will be asked about adverse events, changes in medications and their ability to continue study treatment. These discussions form part of the routine study visit and are not conducted as separate formal or structured interviews. Treatment‐emergent adverse events will be assessed continuously from the first dose through Week 24. Treatment discontinuations, dose interruptions, dose reductions and investigator clinical assessments will be assessed at Baseline and at approximately 4‐weekly study visits through Week 24.]