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 2
Recruiting
- Conditions
- ObesityOverweightOverweight With One Weight Related Comorbidity
- Interventions
- Registration Number
- NCT06965413
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 234
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Tirzepatide RO7204239 Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks. Placebo + Tirzepatide Tirzepatide Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks. RO7204239 low dose + Tirzepatide Tirzepatide Participants will receive RO7204239, low dose, SC, Q4W for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. Placebo + Tirzepatide RO7204239 Matching Placebo Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks. RO7204239 low dose + Tirzepatide RO7204239 Participants will receive RO7204239, low dose, SC, Q4W for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. RO7204239 high dose + Tirzepatide RO7204239 Participants will receive RO7204239, high dose, SC, Q4W along with tirzepatide, given as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. During the treatment extension period participants will be randomized to receive RO7204239 or matching placebo, SC, Q4W for 24 weeks. RO7204239 medium dose + Tirzepatide RO7204239 Participants will receive RO7204239, medium dose, SC, Q4W for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. RO7204239 medium dose + Tirzepatide Tirzepatide Participants will receive RO7204239, medium dose, SC, Q4W for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. RO7204239 high dose + Tirzepatide Tirzepatide Participants will receive RO7204239, high dose, SC, Q4W along with tirzepatide, given as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. During the treatment extension period participants will be randomized to receive RO7204239 or matching placebo, SC, Q4W for 24 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Body Weight Baseline, Week 48
- Secondary Outcome Measures
Name Time Method Absolute Change From Baseline in Body Weight Baseline, Week 48 Change From Baseline in Body Mass Index (BMI) Baseline, Week 48 Change From Baseline in Waist-to-height Ratio Baseline, Week 48 Change From Baseline in Waist Circumference Baseline, Week 48 Change From Baseline in Total Body Fat Mass Measured by Dual-energy X-ray Absorptiometry (DXA) Baseline, Week 48 Change From Baseline in Total Lean Body Mass Measured by DXA Baseline, Week 48 Change From Baseline in Appendicular Lean Mass Measured by DXA at Week 48 Baseline, Week 48 Change From Baseline in Muscle Volume Measured by Magnetic Resonance Imaging (MRI) Baseline, Week 48 Change From Baseline in Muscle Fat Infiltration Measured by MRI Baseline, Week 48 Change From Baseline in Glycated Hemoglobin (HbA1C) Levels Baseline, Week 48 Change From Baseline in Fasting Plasma Glucose Levels Baseline, Week 48 Change From Baseline in Fasting C-peptide and Fasting Insulin Levels Baseline, Week 48 Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Baseline, Week 48 Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) Baseline, Week 48 Apparent Volume of Distribution (Vd/F) of RO7204239 Up to approximately 96 weeks Number of Participants With Anti-drug Antibodies (ADAs) to RO7204239 Up to approximately 96 weeks Change From Baseline in Fasting Lipid Profile Baseline, Week 48 Fasting lipid profile includes total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL cholesterol
Number of Participants With Adverse Events (AEs) Up to approximately 100 weeks Number of Participants With Local and Systemic Injection Reactions Up to approximately 100 weeks Serum Concentrations of RO7204239 Up to approximately 96 weeks Steady-state Trough Concentration (Ctrough,ss) of RO7204239 Up to approximately 96 weeks Half-life (t1/2) of RO7204239 Up to approximately 96 weeks Steady-state Area Under the Concentration-time Curve Over One Dosing Interval (AUCtau,ss) of RO7204239 Up to approximately 96 weeks Steady-state Maximum Concentration (Cmax,ss) of RO7204239 Up to approximately 96 weeks Apparent Clearance (CL/F) of RO7204239 Up to approximately 96 weeks
Trial Locations
- Locations (1)
Juno Research, LLC
🇺🇸Houston, Texas, United States