Phase III Study of RO7795068 in Adults With Obesity or Overweight and Type 2 Diabetes

The primary objective is to evaluate the effect of RO7795068 versus placebo on body weight, measured as percent change from baseline at Week 72. This endpoint is clinically relevant because it quantifies the magnitude of weight reduction in participants with obesity or overweight and type 2 diabetes. Secondary objectives assess additional dimensions of weight management and metabolic control, including the proportions achieving ≥5%, ≥10%, and ≥15% body weight loss at Week 72, absolute change in body weight, change in hemoglobin A1c, achievement of HbA1c thresholds of ≤6.5%, <7%, and <5.7%, change in fasting glucose, change in waist circumference, BMI, and percent weight change by obesity class. Further objectives evaluate cardiovascular and metabolic measures, hunger and satiety, physical functioning, health-related quality of life, urinary incontinence in women with baseline urinary incontinence, albuminuria, and safety and tolerability.

The trial enrolled 1051 participants with obesity or overweight and type 2 diabetes. The study population included adults of both female and male sex, and the age range was 18 years and older. Participants were selected on the basis of a body mass index of at least 27.0 kg/m², a diagnosis of type 2 diabetes with HbA1c between 6.5% and 10%, and stable oral therapy for at least 3 months when applicable. Eligible participants had a history of at least one unsuccessful diet or exercise effort to lose body weight. The population included individuals managed with diet and exercise alone or with oral antihyperglycemic therapy, excluding DPP-4 inhibitors or GLP-1 receptor agonist-based therapy. Willingness and ability to comply with study requirements and to self-administer the study drug, or receive an injection from a trained individual if needed, were also required.

The study is a Phase III, randomized, double-blind, placebo-controlled, parallel-group trial evaluating once-weekly RO7795068 in adults with obesity or overweight and type 2 diabetes. The main objective is to compare RO7795068 with placebo for percent change from baseline in body weight at Week 72. Study participation is expected to last from screening through the end-of-study visit at approximately Week 72. The screening visit is used to confirm eligibility, including demographic criteria, body mass index, glycemic status, and prior weight-loss history, and to establish baseline assessments. After randomization, participants receive study treatment and undergo scheduled follow-up visits for efficacy, safety, laboratory, vital sign, electrocardiographic, and questionnaire assessments. The end-of-study visit is performed at the end of the treatment and observation period to complete final efficacy and safety evaluations. Early termination may occur if a participant withdraws consent, becomes ineligible, cannot comply with protocol requirements, experiences an adverse event or other condition requiring discontinuation, or stops study drug for any reason.

RO7795068 was the investigational treatment in this study. It was administered as a solution for injection by a route of administration not applicable in the source data. The dose was specified as 0 DF dosage form. Administration was once weekly in a randomized, double-blind, parallel-group design. The study evaluated RO7795068 compared with placebo over a 72-week treatment period. Compliance monitoring was based on the scheduled weekly administration in the trial.

The non-experimental treatment was placebo, provided as RO7795068 Placebo. No pharmaceutical form, dose, or route was specified in the source data. Placebo was used in the same double-blind, parallel-group framework as the investigational treatment.

Efficacy will be assessed by percent (%) change from baseline in body weight at Week 72. Secondary efficacy assessments will include achievement of ≥5%, ≥10%, and ≥15% body weight loss at Week 72; change from baseline in body weight, HbA1c, waist circumference, fasting glucose, fasting insulin, LDL cholesterol, HDL cholesterol, triglyceride, systolic blood pressure, waist-to-hip ratio, waist-to-height ratio, BMI, non-HDL cholesterol, VLDL cholesterol, total cholesterol, free fatty acids, diastolic blood pressure, hsCRP, and urinary albumin/creatinine ratio at Week 72; time to achieve ≥5%, ≥10%, and ≥15% weight loss from baseline through Week 72; and achievement of HbA1c thresholds of ≤6.5%, <7%, and <5.7% at Week 72.

Efficacy will also be evaluated using patient-reported outcomes and questionnaire-based measures at Week 72, including the physical functioning domain of the Short Form (36) Health Survey Version 2 Acute Form (SF-36v2 Acute Form), the physical functioning composite and domain scores of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT), the Control of Eating Questionnaire (CoEQ) subscale scores and individual hunger item score, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), and the Patient Global Impression of Change and Patient Global Impression of Severity/Status measures for urinary incontinence and physical functioning. Change from baseline in health-related quality of life domain scores and component summary scores will also be assessed at Week 72.