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

NCT06299098 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: R1033-OB-2288
• Study Type: interventional
• Target: 1,005
• Locations: 2 countries
• Sites: 60

Brief Summary

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)

Conditions

Obesity

Keywords

Obesity without diabetes; Quality of weight loss; Fat mass loss; Lean mass loss

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (21)

• Concentrations of trevogrumab in serum over time

  Up to 75 weeks

• Percent change in total fat mass

  Baseline to week 52

• Percent change in total lean mass

  Baseline to week 52

• Percent change in body weight

  Baseline to week 52

• Change in waist circumference (cm)

  Baseline to week 26

Study Arms (13)

Placebo

PLACEBO COMPARATOR

Part A Randomized 1:1

Drug: Matching Placebo-Part A

Trevogrumab

EXPERIMENTAL

Part A Randomized 1:1

Drug: Trevogrumab-Part A

Arm A0

EXPERIMENTAL

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: Semaglutide; Drug: Matching Placebo-Trevogrumab; Drug: Matching Placebo-Garetosmab

Arm A1

EXPERIMENTAL

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: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab; Drug: Matching Placebo-Garetosmab

Arm B0

EXPERIMENTAL

Part B Sema, moderate-high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1

Drug: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab; Drug: Matching Placebo-Garetosmab

Arm B1

EXPERIMENTAL

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: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Garetosmab

Arm C0

EXPERIMENTAL

Part B Sema, high dose trevo, and IV placebo followed by SC placebo Randomized 1:1:1:1:1:1:1:1

Drug: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab; Drug: Matching Placebo-Garetosmab

Arm C1

EXPERIMENTAL

Part B Sema, high dose trevo, and IV placebo followed by high dose trevo Randomized 1:1:1:1:1:1:1:1

Drug: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Garetosmab

Arm D0

EXPERIMENTAL

Part B Sema, high dose trevo, and garetosmab (gareto) followed by SC placebo Randomized 1:1:1:1:1:1:1:1

Drug: Trevogrumab-Part B and Part C; Drug: Garetosmab; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab

Arm D1

EXPERIMENTAL

Part B Sema, high dose trevo, and gareto followed by high dose trevo Randomized 1:1:1:1:1:1:1:1

Drug: Trevogrumab-Part B and Part C; Drug: Garetosmab; Drug: Semaglutide

Arm 1

EXPERIMENTAL

Part C Sema and SC placebo Randomized 1:2:2

Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab

Arm 2

EXPERIMENTAL

Part C Sema and SC low dose trevo Randomized 1:2:2

Drug: Trevogrumab-Part B and Part C; Drug: Semaglutide; Drug: Matching Placebo-Trevogrumab

Arm 3

EXPERIMENTAL

Part C Sema and SC moderate dose trevo Randomized 1:2:2

Drug: Trevogrumab-Part B and Part C; Drug: Semaglutide

Interventions

Trevogrumab-Part A DRUG

Administered IV or SC in Part A

Also known as: REGN1033, GDF8

Trevogrumab

Trevogrumab-Part B and Part C DRUG

Administered SC in Part B, Part C

Also known as: REGN1033, GDF8

Arm 2; Arm 3; Arm A1; Arm B0; Arm B1; Arm C0; Arm C1; Arm D0; Arm D1

Garetosmab DRUG

Administered IV in Part B

Also known as: REGN2477, Activin A

Arm D0; Arm D1

Semaglutide DRUG

Administered SC in Part B and Part C

Also known as: Wegovy®

Arm 1; Arm 2; Arm 3; Arm A0; Arm A1; Arm B0; Arm B1; Arm C0; Arm C1; Arm D0; Arm D1

Matching Placebo-Part A DRUG

Administered IV or SC in Part A

Placebo

Matching Placebo-Trevogrumab DRUG

Administered SC in Part B and Part C

Arm 1; Arm 2; Arm A0; Arm A1; Arm B0; Arm C0; Arm D0

Matching Placebo-Garetosmab DRUG

Administered IV in Part B

Arm A0; Arm A1; Arm B0; Arm B1; Arm C0; Arm C1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A
• Male or female participants age ≥18 to ≤55 years of age at the time of screening
• BMI ≥18 and ≤32 kg/m2, at the screening visit
• Part B and Part C
• Male or female participants ≥18 to ≤80 years of age at the time of screening
• BMI ≥30 kg/m2, at the screening visit
• History of 1 or more self-reported unsuccessful dietary attempts to lose weight

You may not qualify if:

• History of diabetes (Type 2 or Type 1). History of gestational diabetes is permitted
• Previous bariatric surgery or planned bariatric surgery
• History of hypertrophic cardiomyopathy
• Abnormal electrocardiogram (ECG) findings at screening that meet Cornell voltage criteria for left ventricular hypertrophy
• 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)
• History of poorly controlled hypertension, as defined in the protocol
• 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
• 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
• Has a history of any neuromuscular disorder (eg, multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, etc)

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (60)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Cullman Clinical Trials

Cullman, Alabama, 35055, United States

Location

Foothills Research Center Cct Research

Phoenix, Arizona, 85044, United States

Location

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

ProSciento

Chula Vista, California, 91911, United States

Location

Valiance Clinical Research- Huntington Park

Huntington Park, California, 91356, United States

Location

Velocity, San Diego

La Mesa, California, 91941, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Acclaim Clinical Research

San Diego, California, 92120, United States

Location

Metabolic Institute of America

Tarzana, California, 91356, United States

Location

Valiance Clinical Research

Tarzana, California, 91356, United States

Location

Southwest General Healthcare Center

Fort Myers, Florida, 33907, United States

Location

Westside Center for Clinical Research

Jacksonville, Florida, 32205, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

IMA Clinical Research St. Petersburg

St. Petersburg, Florida, 33709, United States

Location

Precision Clinical Research, LLC

Sunrise, Florida, 33351, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33606, United States

Location

Clinical Research of Central Florida - Bond Clinic

Winter Haven, Florida, 33880, United States

Location

Center for Advanced Research and Education

Gainesville, Georgia, 30501, United States

Location

Balanced Life Health Care Solutions

Lawrenceville, Georgia, 30046, United States

Location

North Georgia Clinical Research

Woodstock, Georgia, 30189, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Elite Clinical Trials LLLP

Blackfoot, Idaho, 83221, United States

Location

Prairie Education and Research Cooperative (PERC)

Springfield, Illinois, 62701, United States

Location

The South Bend Clinic Center for Research

South Bend, Indiana, 46617, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Tandem Clinical Research GI, LLC

Marrero, Louisiana, 70072, United States

Location

IMA Clinical Research Monroe - Armand

Monroe, Louisiana, 71201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Prime Health and Wellness Clinic

Fayette, Mississippi, 39069, United States

Location

Olive Branch Family Medical Center

Olive Branch, Mississippi, 38654, United States

Location

Sky Integrative Medical Center Skycrng

Ridgeland, Mississippi, 39157, United States

Location

Jefferson City Medical Group

Jefferson City, Missouri, 65109, United States

Location

Clinvest Research

Springfield, Missouri, 65807, United States

Location

Mercury Street Medical Group, PLLC

Butte, Montana, 59701, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Accellacare Clinical Research, Raleigh Medical Group

Raleigh, North Carolina, 27609, United States

Location

Accellacare of Salisbury

Salisbury, North Carolina, 28144, United States

Location

Accellacare of Piedmont, Piedmont Healthcare

Statesville, North Carolina, 28625, United States

Location

Pmg Research of Wilmington Llc

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Javara Incorporated at Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Velocity Clinical Research Inc.

Cincinnati, Ohio, 45219, United States

Location

AMR Norman

Norman, Oklahoma, 73069, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Tribe Clinical Research Llc

Greenville, South Carolina, 29607, United States

Location

PMG Research of Charleston

Mt. Pleasant, South Carolina, 29464, United States

Location

Pmg Research of Bristol

Bristol, Tennessee, 37620, United States

Location

Chattanooga Medical Research

Chattanooga, Tennessee, 37412, United States

Location

PMG Research of Knoxville - Merchant Drive

Knoxville, Tennessee, 37912, United States

Location

PMG Research of Knoxville - Emory Road

Knoxville, Tennessee, 37938, United States

Location

Velocity Clinical Research Dallas

Dallas, Texas, 75230, United States

Location

Medresearch Inc

El Paso, Texas, 79902, United States

Location

Valley Institute of Research

Fort Worth, Texas, 76164, United States

Location

Consano Clinical Research

Shavano Park, Texas, 78231, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Health Research of Hampton Roads, Inc.

Newport News, Virginia, 23606, United States

Location

Fundacion de Investigacion (FDI) Clinical Research

San Juan, 00927, Puerto Rico

Location

PRCCI Clinical Research Center

San Juan, 00927, Puerto Rico

Location

Related Links

• Courage Study

MeSH Terms

Conditions

Obesity

Interventions

activin A; semaglutide

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 7, 2024
• Study Start: March 13, 2024
• Primary Completion (Estimated): May 18, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

PR (2); US (58)