A Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity

Phase 2Active Not RecruitingNCT06965413

Hoffmann-La Roche285 enrolled

Overview

The main aim of the study is to assess the effect of RO7204239 in combination with tirzepatide, compared to placebo in combination with tirzepatide, on body weight loss after 48 weeks of treatment in adults with obesity or overweight with at least one weight-related comorbidity, but without diabetes mellitus (DM). The study comprises of a 4-week screening period; a 48-week core treatment period, where all participants will receive tirzepatide as background treatment and will be randomized to one of the 4 treatment arms; a 24-week treatment extension period, where participants will stop treatment with tirzepatide and a 24-week post-treatment follow-up (FU) period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

285

Conditions

Obesity Overweight Overweight With One Weight Related Comorbidity

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * BMI ≥ 30.0 kilograms per square meter (kg/m²) (additional weight-related comorbidities are not required for inclusion) * BMI ≥ 27.0 kg/m² and \< 30.0 kg/m² with at least one weight-related comorbidity such as: hypertension, dyslipidemia, obstructive sleep apnea and any cardiovascular disease * History of at least one self-reported unsuccessful dietary or exercise effort to lose body weight * Weight stability: self-reported change in body weight less than 5 kilograms (kg) (11 pounds \[lbs\]) within 3 months prior to screening Exclusion Criteria: * Prior history or diagnosis of DM * Presence of non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy or diabetic macular edema * Have obesity induced by other endocrinologic disorders * Participation in unbalanced/extreme diets * Prior or planned surgical treatment for obesity * Endoscopic and/or device-based therapy for obesity or device removal within 6 months prior to screening * Have a known clinically significant gastric emptying abnormality * Have any of the following cardiovascular conditions within 6 months prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or hospitalization due to congestive heart failure (CHF) * Have evidence of significant active, uncontrolled cardiovascular, autoimmune, endocrine, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, a neurological or psychiatric condition, or a history of any neuromuscular disorder or autoimmune/inflammatory disorders that may cause muscle wasting or medical condition capable of constituting a risk when taking the study medication or interfering with the interpretation of data, as judged by the investigator at screening * Have evidence of a significant, uncontrolled endocrine abnormality * Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy * Have evidence of a significant, active autoimmune abnormality * Have anemia * Have signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)

Outcomes

Primary Outcomes

Percent Change From Baseline in Body Weight

Time frame: Baseline, Week 48

Secondary Outcomes

Absolute Change From Baseline in Body Weight

Time frame: Baseline, Week 48

Change From Baseline in Body Mass Index (BMI)

Time frame: Baseline, Week 48

Change From Baseline in Waist-to-height Ratio

Time frame: Baseline, Week 48

Change From Baseline in Waist Circumference

Time frame: Baseline, Week 48

Change From Baseline in Total Body Fat Mass Measured by Dual-energy X-ray Absorptiometry (DXA)

Time frame: Baseline, Week 48

Change From Baseline in Total Lean Body Mass Measured by DXA

Time frame: Baseline, Week 48

Change From Baseline in Appendicular Lean Mass Measured by DXA at Week 48

Time frame: Baseline, Week 48

Change From Baseline in Muscle Volume Measured by Magnetic Resonance Imaging (MRI)

Time frame: Baseline, Week 48

Change From Baseline in Muscle Fat Infiltration Measured by MRI

Time frame: Baseline, Week 48

Change From Baseline in Glycated Hemoglobin (HbA1C) Levels

Time frame: Baseline, Week 48

Change From Baseline in Fasting Plasma Glucose Levels

Time frame: Baseline, Week 48

Change From Baseline in Fasting C-peptide and Fasting Insulin Levels

Time frame: Baseline, Week 48

Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

Time frame: Baseline, Week 48

Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)

Time frame: Baseline, Week 48

Change From Baseline in Fasting Lipid Profile

Fasting lipid profile includes total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL cholesterol

Time frame: Baseline, Week 48

Number of Participants With Adverse Events (AEs)

Time frame: Up to approximately 100 weeks

Number of Participants With Local and Systemic Injection Reactions

Time frame: Up to approximately 100 weeks

Serum Concentrations of RO7204239