Phase III Study of RO7795068 for Weight Management in Adults With Obesity or Overweight Without Type 2 Diabetes

The primary objective is to assess the effect of RO7795068 compared with placebo on weight management as measured by the percent change from baseline in body weight at Week 72, providing a definitive efficacy endpoint for obesity or overweight participants without type 2 diabetes.

Secondary objectives include: – evaluation of the proportion of participants achieving ≥5 %, ≥10 %, ≥15 %, ≥20 %, ≥25 % and ≥30 % body‑weight loss at Week 72; – change from baseline in absolute body weight (kg); – change in waist circumference and BMI by obesity class; – time to reach each predefined weight‑loss threshold; – assessment of glycemic control and, in a pooled‑dose analysis, glycemic outcomes in participants with prediabetes; – impact on cardiovascular and metabolic measures; – effects on hunger, satiety, urinary incontinence, and physical functioning, including sub‑analyses in subjects with impaired physical function; – evaluation of health‑related quality of life; – analysis of body‑composition changes by MRI in the substudy cohort; – overall safety and tolerability of RO7795068.

The trial enrolled 1,246 adult participants (≥18 years) of both sexes. Eligible individuals had a body mass index (BMI) of ≥30 kg/m², or 27–30 kg/m² with at least one weight‑related comorbidity such as prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. All subjects were classified as having obesity or being overweight without type 2 diabetes and reported at least one prior unsuccessful diet or exercise attempt. Enrollment required the ability to comply with study procedures, self‑administer the investigational product, and meet contraception requirements. The population was selected on the basis of these inclusion criteria, encompassing a generally healthy adult cohort aside from the specified metabolic and cardiovascular conditions, with no restriction on gender and inclusion of vulnerable participants as defined by the protocol.

The study is a Phase III, randomized, double‑blind, placebo‑controlled, parallel‑group trial evaluating once‑weekly RO7795068 in adults with obesity or overweight without type 2 diabetes. Participants undergo a screening visit to confirm eligibility, a baseline/randomization visit, and then receive weekly injections of study drug or matching placebo for 72 weeks; the primary efficacy endpoint is percent change in body weight at week 72. Efficacy and safety assessments are scheduled at weeks 12, 24, 36, 48, 60, and the end‑of‑study visit at week 72, with additional routine visits for dosing and monitoring. The total participant involvement, including screening, is approximately 78 weeks. Early termination may occur for withdrawal of consent, serious adverse events, pregnancy, non‑adherence to dosing, or major protocol violations.

The investigational product, identified as RO7795068, is supplied as a solution for injection. The formulation is designated with a dose of “0” in the DF dosage form and the route of administration is listed as not applicable. According to the study protocol, the product is to be administered once weekly for the duration of the trial. Dosing is performed under controlled conditions, with each administration recorded in the study drug accountability log to ensure compliance monitoring.

The control arm utilizes a matching placebo, labeled “RO7795068 Placebo,” which contains no active substances. The placebo is presented as a non‑applicable formulation (N/A) and is administered on the same weekly schedule as the active product. Placebo administration follows identical procedures to the active arm, including documentation of each dose in the drug accountability records to maintain blinding and monitor adherence.

Efficacy will be evaluated primarily by the Percent (%) change from baseline in body weight at Week 72, measured with a calibrated scale after an overnight fast. Secondary efficacy parameters include categorical weight‑loss thresholds (≥5 %, ≥10 %, ≥15 %, ≥20 %, ≥25 % and ≥30 % loss at Week 72), absolute change in body weight (kg), waist circumference (cm), waist‑to‑hip and waist‑to‑height ratios, body‑mass index, and total lean and adipose tissue volumes. Metabolic and cardiovascular biomarkers such as fasting glucose, fasting insulin, LDL‑C, HDL‑C, triglycerides, total cholesterol, non‑HDL‑C, VLDL‑C, free fatty acids, high‑sensitivity C‑reactive protein, systolic and diastolic blood pressure, and hsCRP will be obtained from fasting blood samples and vital‑sign assessments. Health‑related quality‑of‑life and patient‑reported outcomes will be captured using validated instruments, including the Short Form (36) Health Survey Version 2 Acute Form (SF‑36v2 Acute Form), the Impact of Weight on Quality of Life‑Lite Clinical Trials Version (IWQoL‑Lite‑CT), the Control of Eating Questionnaire (CoEQ) subscales, the International Consultation on Incontinence Questionnaire‑Urinary Incontinence Short Form (ICIQ‑UI SF), and Patient Global Impression of Change (PGI‑C) and Severity (PGI‑S) items for urinary incontinence and physical functioning. Additional safety‑related patient‑reported measures include the Columbia‑Suicide Severity Rating Scale (C‑SSRS) and the Patient Health Questionnaire‑9 (PHQ‑9).

All efficacy assessments will be performed at baseline and at the Week 72 visit. Body‑weight and anthropometric measurements will be taken in triplicate and averaged. Laboratory analyses will follow standard clinical laboratory procedures with central laboratory oversight. Patient‑reported outcomes will be completed electronically using the study‑specific data capture system. Data will be analyzed using predefined statistical models appropriate for continuous and categorical endpoints, with adjustments for baseline values where applicable.