Trevogrumab + Garetosmab + Semaglutide for Obesity

(COURAGE Trial)

Recruiting at 59 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Diabetes, Bariatric surgery, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

999 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination Trevogrumab + Garetosmab + Semaglutide for obesity?

Semaglutide, one of the drugs in the combination, has been shown to help people lose significant weight, with studies reporting weight loss of 14.9%-17.4% over 68 weeks. It also improves heart health and physical function, making it a promising option for managing obesity. ^{1 2 3 4 5}

How does the drug Trevogrumab + Garetosmab + Semaglutide differ from other obesity treatments?

This drug combination is unique because it includes semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, which has shown significant weight loss results, reducing body weight by about 15% over 68 weeks. Semaglutide is already approved for chronic weight management and is known for its effectiveness in improving cardiovascular risk factors, making it a promising component in this new treatment for obesity. ^{1 2 3 5 6}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for adults aged 18-55 with a BMI of 18-32 (Part A), and those aged 18-80 with obesity, defined as a BMI over 30 (Part B). Participants should have tried to lose weight unsuccessfully before. It's not clear what excludes someone from joining.

Inclusion Criteria

You have been diagnosed with Nonalcoholic Steatohepatitis

I am between 18 and 55 years old with a BMI between 18 and 32.

I am between 18 and 80 years old, have a BMI of 30 or more, and have tried to lose weight through diet without success.

Exclusion Criteria

I haven't had any cancer except for non-spreading skin cancer in the last 5 years.

I have a history of a neuromuscular disorder.

I have had or am planning to have weight loss surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A Treatment

Healthy participants receive study drugs to assess safety and tolerability

7 weeks

Part B Treatment

Participants with obesity receive study drugs to assess safety and effectiveness

52 weeks

Part C Treatment

Continuation of treatment in participants with obesity to further assess safety and effectiveness

Up to 75 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Garetosmab
• Trevogrumab

Trial Overview The study tests trevogrumab alone or combined with garetosmab and semaglutide in two parts: Part A focuses on safety in healthy individuals; Part B examines effectiveness for weight loss in obese participants using various drug combinations.

Participant Groups

Group I: Trevogrumab Experimental Treatment 1 Intervention

Part A Randomized 1:1

Group II: Arm D1 Experimental Treatment 3 Interventions

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

Group III: Arm D0 Experimental Treatment 4 Interventions

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

Group IV: Arm C1 Experimental Treatment 3 Interventions

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

Group V: Arm C0 Experimental Treatment 4 Interventions

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

Group VI: Arm B1 Experimental Treatment 3 Interventions

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

Group VII: Arm B0 Experimental Treatment 4 Interventions

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

Group VIII: Arm A1 Experimental Treatment 4 Interventions

Part B Sema and SC placebo and IV placebo followed by high dose trevogrumab (trevo) Randomized 1:1:1:1:1:1:1:1

Group IX: Arm A0 Experimental Treatment 3 Interventions

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

Group X: Arm 3 Experimental Treatment 3 Interventions

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

Group XI: Arm 2 Experimental Treatment 3 Interventions

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

Group XII: Arm 1 Experimental Treatment 2 Interventions

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

Group XIII: Placebo Placebo Group 1 Intervention

Part A Randomized 1:1

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Semaglutide, approved by the FDA on June 4, 2021, is the first new drug for chronic weight management in adults with obesity or overweight since 2014, specifically targeting those with a BMI of 27 or greater and at least one weight-related condition.

This medication is intended to be used alongside a weight management program that includes a reduced-calorie diet and increased physical activity, highlighting its role as part of a comprehensive approach to weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Mares, AC., Chatterjee, S., Mukherjee, D.[2023]

Setmelanotide has been approved for treating specific genetic conditions that cause obesity, representing a significant step in personalized medicine for obesity management.

Semaglutide, which has shown to produce approximately twice the weight loss compared to older antiobesity medications, is under regulatory review for treating obesity and is already used for diabetes, highlighting its dual efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? Ryan, DH.[2021]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

In a study involving participants with a BMI of 27 kg/m² or higher, semaglutide led to significant weight loss of -16.2% for those with a BMI <35 and -14.0% for those with a BMI ≥35 after 68 weeks, both significantly better than placebo.

Semaglutide also positively impacted cardiometabolic risk factors across all subgroups, including those with obesity-related comorbidities like prediabetes and high cardiovascular disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial. McGowan, BM., Houshmand-Oeregaard, A., Laursen, PN., et al.[2023]

In the STEP clinical trial program, participants with obesity who received once-weekly semaglutide 2.4 mg experienced significant weight loss, averaging between 14.9% and 17.4% over 68 weeks, with 69%-79% achieving at least 10% weight loss compared to only 12%-27% with placebo.

Semaglutide 2.4 mg also led to improvements in cardiometabolic risk factors and had a consistent safety profile, primarily involving gastrointestinal side effects, indicating its potential as an effective treatment for obesity and related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. Bergmann, NC., Davies, MJ., Lingvay, I., et al.[2023]

Obesity is a major public health concern, with projections indicating that over 1.1 billion individuals will be affected by 2030, highlighting the urgent need for effective treatments.

GLP-1 receptor agonists, particularly semaglutide, are at the forefront of clinical development for obesity treatment, showing promise in improving metabolic health and potentially serving as a benchmark for future anti-obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Jepsen, MM., Christensen, MB.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. [2023]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. [2022]