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

NCT06965413 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: BC455382024-519561-22-00
• Study Type: interventional
• Target: 285
• Locations: 4 countries
• Sites: 35

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.

Conditions

Obesity; Overweight; Overweight With One Weight Related Comorbidity

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Body Weight

  Baseline, Week 48

Secondary Outcomes (25)

• 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

Study Arms (4)

Placebo + Tirzepatide

ACTIVE COMPARATOR

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; Drug: RO7204239 Matching Placebo; Drug: Tirzepatide

RO7204239 low dose + Tirzepatide

EXPERIMENTAL

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; Drug: Tirzepatide

RO7204239 medium dose + Tirzepatide

EXPERIMENTAL

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; Drug: Tirzepatide

RO7204239 high dose + Tirzepatide

EXPERIMENTAL

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; Drug: Tirzepatide

Interventions

RO7204239 DRUG

RO7204239 or matching placebo will be administered as per the schedule specified in the arms.

Placebo + Tirzepatide; RO7204239 high dose + Tirzepatide; RO7204239 low dose + Tirzepatide; RO7204239 medium dose + Tirzepatide

RO7204239 Matching Placebo DRUG

RO7204239 matching placebo will be administered as per the schedule specified in the arm.

Placebo + Tirzepatide

Tirzepatide DRUG

Tirzepatide will be administered as per the schedule specified in the arms.

Placebo + Tirzepatide; RO7204239 high dose + Tirzepatide; RO7204239 low dose + Tirzepatide; RO7204239 medium dose + Tirzepatide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (35)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Encompass Clinical Research

Spring Valley, California, 91978, United States

Location

K2 Medical Research-Winter Garden

Clermont, Florida, 34711, United States

Location

Rophe Adult and Pediatric Medicine/SKYCRNG

Union City, Georgia, 30291, United States

Location

Accellacare of Duly Health and Care

Oak Lawn, Illinois, 60453, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

Accellacare of Salisbury

Salisbury, North Carolina, 28144, United States

Location

Accellacare of Piedmont Healthcare

Statesville, North Carolina, 28625, United States

Location

Accellacare of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

Accellacare Research of Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

NexGen Research

Lima, Ohio, 45801, United States

Location

Accellacare of Bristol/ Internal Medicine & Pediatrics

Bristol, Tennessee, 37620, United States

Location

Accellacare of Knoxville

Knoxville, Tennessee, 37912, United States

Location

Clinical Research Associates

Nashville, Tennessee, 37203, United States

Location

Texas Diabetes & Endocrinology, P.A.

Austin, Texas, 78731, United States

Location

Juno Research, LLC

Houston, Texas, 77040, United States

Location

Consano Clinical Research

Shavano Park, Texas, 78231, United States

Location

Velocity Clinical Research (Impact Research Institute)

Waco, Texas, 76710, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Centrum Badan Klinicznych PI-House sp. z o.o.

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

Centrum Medyczne ALL-MED

Krakow, 30-033, Poland

Location

Ekamed sp. z o.o.

Lublin, 20-718, Poland

Location

ETG Warszawa

Warsaw, 02-677, Poland

Location

Universidad de Sevilla - Hospital Universitario Virgen Macarena

Seville, Barcelona, 41009, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Vithas Nisa Sevilla

Castilleja de la Cuesta, Granada, 41950, Spain

Location

Hospital San Rafael A Coruna

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Fylde Coast Clinical Research at Layton Medical Centre

Blackpool, Lancashire, FY3 7EN, United Kingdom

Location

University Hospitals of Leicester NHS Trust - Leicester General Hospital (LGH)

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

Accellacare Yorkshire

Shipley, Yorkshire, BD18 3SA, United Kingdom

Location

Accellacare Warwickshire

Coventry, CV3 4FJ, United Kingdom

Location

Accellacare North London

Northwood, HA6 2RN, United Kingdom

Location

Accellacare South London

Orpington, BR5 3QG, United Kingdom

Location

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2025
• First Posted: May 11, 2025
• Study Start: May 5, 2025
• Primary Completion (Estimated): August 24, 2026
• Study Completion (Estimated): July 23, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (6); US (19); GB (6); PL (4)