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 (GYMINDA)

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

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 Overview

• Status: Active, not recruiting
• Conditions: Obesity; Overweight; Overweight With One Weight Related Comorbidity
• Intervention / Treatment: Drug: RO7204239; Drug: RO7204239 Matching Placebo; Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Lublin, Poland, 20-718
    • Ekamed Sp. z o.o.
  • Warsaw, Poland, 02-677
    • ETG Warszawa
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-033
      • Centrum Medyczne ALL-MED
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-546
      • Penta Hospials Badania Kliniczne Gdansk
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Barcelona
    • Seville, Barcelona, Spain, 41009
      • Universidad de Sevilla - Hospital Universitario Virgen Macarena
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Instituto De Investigacion Marques De Valdecilla (IDIVAL)
  • Granada
    • Castilleja de la Cuesta, Granada, Spain, 41950
      • Hospital Vithas Nisa Sevilla
  • LA Coruna
    • A Coruña, LA Coruna, Spain, 15006
      • Hospital San Rafael A Coruna
• United Kingdom
  • Coventry, United Kingdom, CV3 4FJ
    • Accellacare Warwickshire
  • Northwood, United Kingdom, HA6 2RN
    • Accellacare North London
  • Orpington, United Kingdom, BR5 3QG
    • Accellacare South London
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 7EN
      • Fylde Coast Clinical Research at Layton Medical Centre
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • University Hospitals of Leicester NHS Trust - Leicester General Hospital (LGH)
  • Yorkshire
    • Shipley, Yorkshire, United Kingdom, BD18 3SA
      • Accellacare Yorkshire
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
  • California
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Florida
    • Clermont, Florida, United States, 34711
      • K2 Medical Research-Winter Garden
  • Georgia
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Accellacare of Duly Health and Care
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Accellacare of Salisbury
    • Statesville, North Carolina, United States, 28625
      • Accellacare of Piedmont Healthcare
    • Wilmington, North Carolina, United States, 28401
      • Accellacare of Wilmington, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • Accellacare Research of Winston Salem
  • Ohio
    • Lima, Ohio, United States, 45801
      • Nexgen Research
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Accellacare of Bristol/ Internal Medicine & Pediatrics
    • Knoxville, Tennessee, United States, 37912
      • Accellacare of Knoxville
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Diabetes & Endocrinology, P.A.
    • Houston, Texas, United States, 77040
      • Juno Research, LLC
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research
    • Waco, Texas, United States, 76710
      • Velocity Clinical Research (Impact Research Institute)
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo + 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.	Drug: RO7204239; RO7204239 or matching placebo will be administered as per the schedule specified in the arms.; Drug: RO7204239 Matching Placebo; RO7204239 matching placebo will be administered as per the schedule specified in the arm.; Drug: Tirzepatide; Tirzepatide will be administered as per the schedule specified in the arms.
Experimental: RO7204239 high dose + 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.	Drug: RO7204239; RO7204239 or matching placebo will be administered as per the schedule specified in the arms.; Drug: Tirzepatide; Tirzepatide will be administered as per the schedule specified in the arms.
Experimental: RO7204239 low dose + Tirzepatide; Participants will receive RO7204239, low dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the 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.	Drug: RO7204239; RO7204239 or matching placebo will be administered as per the schedule specified in the arms.; Drug: Tirzepatide; Tirzepatide will be administered as per the schedule specified in the arms.
Experimental: RO7204239 medium dose + Tirzepatide; Participants will receive RO7204239, medium dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the 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.	Drug: RO7204239; RO7204239 or matching placebo will be administered as per the schedule specified in the arms.; Drug: Tirzepatide; Tirzepatide will be administered as per the schedule specified in the arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Body Weight	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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	Baseline, Week 48
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Actual): September 3, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 2, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: BC45538; 2024-519561-22-00 (Registry Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No