A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss, Fat Loss, and Lean Mass Preservation (COURAGE)

A Randomized, Double-Blind Study of The Efficacy and Safety of Trevogrumab, With or Without Garetosmab, in Addition to Semaglutide in Patients With Obesity

This study is researching experimental drugs called trevogrumab and garetosmab (called "study drugs") in combination with another drug, semaglutide (Wegovy®). This study will be done in 3 parts, Part A, Part B, and Part C where different study drugs will be tested.

Part A of the study is focused on healthy participants. Part B and C of the study is focused on participants with obesity.

The aim of Part A of the study is to see how safe and tolerable the study drug is in healthy participants. The aim of Part B and Part C of the study is to see how safe and effective the study drug is when combined with Wegovy.

Parts A, B, and C of the study are looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Matching Placebo-Part A; Drug: Trevogrumab-Part A; Drug: Matching Placebo-Garetosmab; Drug: Garetosmab; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab; Drug: Trevogrumab-Part B and Part C

Detailed Description

Part A Healthy Volunteers

Part B and Part C (starts after treatment for Part A has completed) Participants with Obesity

• Study Type: Interventional
• Enrollment (Actual): 1005
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • PRCCI Clinical Research Center
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion (FDI) Clinical Research
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
    • Cullman, Alabama, United States, 35055
      • Cullman Clinical Trials
  • Arizona
    • Phoenix, Arizona, United States, 85044
      • Foothills Research Center Cct Research
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Chula Vista, California, United States, 91911
      • ProSciento
    • Huntington Park, California, United States, 91356
      • Valiance Clinical Research- Huntington Park
    • La Mesa, California, United States, 91941
      • Velocity, San Diego
    • Sacramento, California, United States, 95821
      • Northern California Research
    • San Diego, California, United States, 92120
      • Acclaim Clinical Research
    • Tarzana, California, United States, 91356
      • Metabolic Institute of America
    • Tarzana, California, United States, 91356
      • Valiance Clinical Research
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Southwest General Healthcare Center
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • St. Petersburg, Florida, United States, 33709
      • IMA Clinical Research St. Petersburg
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research, LLC
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida, Inc.
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida - Bond Clinic
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research and Education
    • Lawrenceville, Georgia, United States, 30046
      • Balanced Life Health Care Solutions
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials LLLP
  • Illinois
    • Springfield, Illinois, United States, 62701
      • Prairie Education and Research Cooperative (PERC)
  • Indiana
    • South Bend, Indiana, United States, 46617
      • The South Bend Clinic Center for Research
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research GI, LLC
    • Monroe, Louisiana, United States, 71201
      • IMA Clinical Research Monroe - Armand
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Fayette, Mississippi, United States, 39069
      • Prime Health and Wellness Clinic
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
    • Ridgeland, Mississippi, United States, 39157
      • Sky Integrative Medical Center Skycrng
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Jefferson City Medical Group
    • Springfield, Missouri, United States, 65807
      • Clinvest Research
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Accellacare Clinical Research, Raleigh Medical Group
    • Salisbury, North Carolina, United States, 28144
      • Accellacare of Salisbury
    • Statesville, North Carolina, United States, 28625
      • Accellacare of Piedmont, Piedmont Healthcare
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington LLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
    • Winston-Salem, North Carolina, United States, 27157
      • Javara Incorporated at Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Velocity Clinical Research Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • AMR Norman
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research LLC
    • Mt. Pleasant, South Carolina, United States, 29464
      • PMG Research of Charleston
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Pmg Research of Bristol
    • Chattanooga, Tennessee, United States, 37412
      • Chattanooga Medical Research
    • Knoxville, Tennessee, United States, 37912
      • PMG Research of Knoxville - Merchant Drive
    • Knoxville, Tennessee, United States, 37938
      • PMG Research of Knoxville - Emory Road
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research Dallas
    • El Paso, Texas, United States, 79902
      • Medresearch Inc
    • Fort Worth, Texas, United States, 76164
      • Valley Institute of Research
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria

Part A

1. Male or female participants age ≥18 to ≤55 years of age at the time of screening

2. BMI ≥18 and ≤32 kg/m2, at the screening visit

   Part B and Part C

3. Male or female participants ≥18 to ≤80 years of age at the time of screening
4. BMI ≥30 kg/m2, at the screening visit
5. History of 1 or more self-reported unsuccessful dietary attempts to lose weight

Key Exclusion Criteria

1. History of diabetes (Type 2 or Type 1). History of gestational diabetes is permitted
2. Previous bariatric surgery or planned bariatric surgery
3. History of hypertrophic cardiomyopathy
4. Abnormal electrocardiogram (ECG) findings at screening that meet Cornell voltage criteria for left ventricular hypertrophy
5. Any malignancy in the past 5 years prior to screening (except for nonmelanoma skin cancer that has been resected with no evidence of metastatic disease for 3 years prior to screening)
6. History of poorly controlled hypertension, as defined in the protocol
7. Have a history of any other condition (such as known drug abuse, alcohol abuse, diagnosed eating disorder, or a severe mental illness) that, in the opinion of the investigator, may preclude the participant from following and completing the protocol
8. Have history of use of marijuana/tetrahydrocannabinol (THC) within 90 days prior to Visit 1 of enrollment and are unwilling to abstain from marijuana/THC use during the trial
9. Has a history of any neuromuscular disorder (eg, multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, etc)

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Part A Randomized 1:1	Drug: Matching Placebo-Part A; Administered IV or SC in Part A
Experimental: Trevogrumab; Part A Randomized 1:1	Drug: Trevogrumab-Part A; Administered IV or SC in Part A; Other Names: REGN1033; GDF8
Experimental: Arm A0; Part B Semaglutide (sema) and subcutaneous (SC) placebo and intravenous (IV) placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C
Experimental: Arm A1; Part B Sema and SC placebo and IV placebo followed by high dose trevogrumab (trevo) Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm C0; Part B Sema, high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm C1; Part B Sema, high dose trevo, and IV placebo followed by high dose trevo Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm D0; Part B Sema, high dose trevo, and garetosmab (gareto) followed by SC placebo Randomized 1:1:1:1:1:1:1:1	Drug: Garetosmab; Administered IV in Part B; Other Names: REGN2477; Activin A; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm D1; Part B Sema, high dose trevo, and gareto followed by high dose trevo Randomized 1:1:1:1:1:1:1:1	Drug: Garetosmab; Administered IV in Part B; Other Names: REGN2477; Activin A; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm B0; Part B Sema, moderate-high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm B1; Part B Sema, moderate-high dose trevo, and IV placebo followed by high dose trevo Randomized 1:1:1:1:1:1:1:1	Drug: Matching Placebo-Garetosmab; Administered IV in Part B; Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm 1; Part C Sema and SC placebo Randomized 1:2:2	Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C
Experimental: Arm 2; Part C Sema and SC low dose trevo Randomized 1:2:2	Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Matching Placebo-Trevogrumab; Administered SC in Part B and Part C; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8
Experimental: Arm 3; Part C Sema and SC moderate dose trevo Randomized 1:2:2	Drug: Semaglutide; Administered SC in Part B and Part C; Other Names: Wegovy®; Drug: Trevogrumab-Part B and Part C; Administered SC in Part B, Part C; Other Names: REGN1033; GDF8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Part A	Baseline to week 7
Severity of TEAEs	Part A	Baseline to week 7
Percent change in total fat mass	Part B	Baseline to week 26
Percent change in total lean mass	Part B	Baseline to week 26
Percent change in body weight	Part B	Baseline to week 26
Percent change in total fat mass	Part C	Baseline to week 52
Percent change in total lean mass	Part C	Baseline to week 52
Percent change in body weight	Part C	Baseline to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in total fat mass	Part B	Baseline to week 52
Percent change in body weight	Part B	Baseline to week 52
Percent change in total lean mass	Part B	Baseline to week 52
Percent change in fasting serum triglycerides	Part B	Baseline to week 26
Percent change in total cholesterol	Part B	Baseline to week 26
Percent change in Apolipoprotein B (Apo B)	Part B	Baseline to week 26
Concentrations of garetosmab in serum over time	Part B	Up to 75 weeks
Incidence of ADAs to garetosmab after repeated doses over time	Part B	Up to 75 weeks
Concentrations of trevogrumab in serum over time	Part A, Part B, and Part C	Up to 75 weeks
Incidence of anti-drug antibodies (ADA) to trevogrumab after repeated doses over time	Part B and Part C	Up to 75 weeks
Incidence of TEAEs	Part B and Part C	Up to 75 weeks
Severity of TEAEs	Part B and Part C	Up to 75 weeks
Change in waist circumference (cm)	Part B and Part C	Baseline to week 26
Change in waist circumference (cm)	Part C	Baseline to week 52
Percent change in Low-Density Lipoprotein Cholesterol (LDL-C)	Part B	Baseline to week 26
Percent change in total fat mass	Part C	Baseline to week 26
Percent change in total lean mass	Part C	Baseline to week 26
Percent change in body weight	Part C	Baseline to week 26
Concentration of total Growth Differentiation Factor (GDF) 8 in serum over time	Part C	Up to 75 weeks
Magnitude of ADAs to trevogrumab over time	Part B and Part C	Up to 75 weeks
Magnitude of ADAs to garetosmab over time	Part B	Up to 75 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Courage Study

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2024
• Primary Completion (Estimated): May 18, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Fat mass loss; Obesity without diabetes; Quality of weight loss; Lean mass loss
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide; activin A
• Other Study ID Numbers: R1033-OB-2288

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy.

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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