Clinical trial NCT06965413: 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
Official title: A Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Assess Efficacy, Safety, and Tolerability of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obesity
Overweight
Overweight With One Weight Related Comorbidity
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-05-11
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Percent Change From Baseline in Body Weight
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Absolute Change From Baseline in Body Weight
timeFrame: Baseline, Week 48
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Waist-to-height Ratio
timeFrame: Baseline, Week 48
measure: Change From Baseline in Waist Circumference
timeFrame: Baseline, Week 48
measure: Change From Baseline in Total Body Fat Mass Measured by Dual-energy X-ray Absorptiometry (DXA)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Total Lean Body Mass Measured by DXA
timeFrame: Baseline, Week 48
measure: Change From Baseline in Appendicular Lean Mass Measured by DXA at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Muscle Volume Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Muscle Fat Infiltration Measured by MRI
timeFrame: Baseline, Week 48
measure: Change From Baseline in Glycated Hemoglobin (HbA1C) Levels
timeFrame: Baseline, Week 48
measure: Change From Baseline in Fasting Plasma Glucose Levels
timeFrame: Baseline, Week 48
measure: Change From Baseline in Fasting C-peptide and Fasting Insulin Levels
timeFrame: Baseline, Week 48
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)
timeFrame: Baseline, Week 48
measure: Change From Baseline in Fasting Lipid Profile
timeFrame: Baseline, Week 48
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 100 weeks
measure: Number of Participants With Local and Systemic Injection Reactions
timeFrame: Up to approximately 100 weeks
measure: Serum Concentrations of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Steady-state Trough Concentration (Ctrough,ss) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Half-life (t1/2) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Steady-state Area Under the Concentration-time Curve Over One Dosing Interval (AUCtau,ss) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Steady-state Maximum Concentration (Cmax,ss) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Apparent Clearance (CL/F) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Apparent Volume of Distribution (Vd/F) of RO7204239
timeFrame: Up to approximately 96 weeks
measure: Number of Participants With Anti-drug Antibodies (ADAs) to RO7204239
timeFrame: Up to approximately 96 weeks
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Orlando
country: United States
facility: K2 Medical Research South Orlando, LLC
state: Florida
city: Union City
country: United States
facility: Rophe Adult and Pediatric Medicine/SKYCRNG
state: Georgia
city: Statesville
country: United States
facility: Accellacare of Piedmont Healthcare
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare of Wilmington, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Accellacare Research of Winston Salem
state: North Carolina
city: Bristol
country: United States
facility: Accellacare of Bristol/ Internal Medicine & Pediatrics
state: Tennessee
city: Knoxville
country: United States
facility: Accellacare of Knoxville
state: Tennessee
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: