Trevogrumab + Garetosmab + Semaglutide for Obesity

(COURAGE Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two experimental drugs, trevogrumab and garetosmab, combined with semaglutide (Wegovy®) for treating obesity. Part A assesses the safety of the drugs in healthy participants, while Parts B and C evaluate their potential for weight loss in individuals with obesity. The study will also monitor side effects and the body's response to these drugs. Individuals with a BMI of 30 or more, who have unsuccessfully tried to lose weight through diet, and do not have diabetes may be suitable for Parts B and C. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to advancements in obesity treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of trevogrumab and garetosmab has been tested for safety, with no major safety issues found in recipients. Previous studies suggest that these drugs are generally well-tolerated when used together. However, health authorities have not yet officially reviewed the safety and effectiveness of these drugs. In contrast, the FDA has already approved semaglutide for other uses, such as weight management, indicating its well-known safety in humans. Overall, current data suggests the treatment appears safe, but ongoing studies aim to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Trevogrumab and Garetosmab for obesity because these treatments represent a novel approach compared to existing options like lifestyle changes, medications such as orlistat, and GLP-1 agonists like semaglutide. Trevogrumab and Garetosmab are monoclonal antibodies that target specific pathways involved in fat accumulation and metabolism. Unlike traditional obesity treatments, which often focus on appetite suppression or calorie absorption, these drugs aim to modulate the body's underlying biological processes. This unique mechanism of action could potentially offer a more effective way to manage obesity, especially for individuals who have not responded well to conventional therapies.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that combining semaglutide with trevogrumab, which targets the protein myostatin, can enhance weight loss in people with obesity. In this trial, some participants will receive this combination. Studies have found that it not only increases fat loss but also preserves muscle, which is often lost during weight loss. Specifically, it reduces muscle loss by 50%–80% compared to using semaglutide alone. This treatment aids in weight loss while maintaining muscle, which is crucial for overall health and metabolism. These findings offer promising evidence for the effectiveness of this treatment combination in managing obesity. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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, 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]

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]

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]

Citations

1. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/results-phase-2-courage-trial-demonstrating-potential-improve

Results from Phase 2 COURAGE Trial Demonstrating ... Complete 26-week results further demonstrate that combining semaglutide with trevogrumab (anti-GDF8/anti-myostatin) helped prevent about ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06299098

NCT06299098 | A Study to Test if Trevogrumab or ... This study is researching experimental drugs called trevogrumab and garetosmab (called study drugs) in combination with another drug, semaglutide (Wegovy).

3. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/interim-results-ongoing-phase-2-courage-trial-confirm-potential

Interim Results from Ongoing Phase 2 COURAGE Trial ... The trial demonstrated that approximately 35% of semaglutide-induced weight loss was due to loss of lean mass.

4. pharmexec.com pharmexec.com/view/regeneron-semaglutide-trevogrumab-demonstrates-superior-fat-loss-reduced-muscle-wasting-obesity-trial

Regeneron's Semaglutide Plus Trevogrumab Combo ... Results from the Phase II COURAGE trial show that Regeneron's combination of semaglutide plus trevogrumab significantly enhanced fat loss while preserving lean ...

5. pace-cme.org pace-cme.org/news/combination-of-semaglutide-and-muscle-preserving-antibodies-helps-preserve-lean-mass/2474952/

Combination of semaglutide and muscle-preserving ... The combination of semaglutide and muscle-preserving antibodies in patients with obesity mitigated lean mass loss by 50%–80%, while further promoting loss of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06970405

NCT06970405 | Study of Safety and Effects of Garetosmab ... The study is focused on otherwise healthy participants with obesity. The aim of the study is to see how safe and tolerable the study drug is. The study is ...

7. diabetesjournals.org diabetesjournals.org/diabetes/article/73/Supplement_1/34-OR/154774/34-OR-The-Effect-of-Combined-Activin-A-and

34-OR: The Effect of Combined Activin A and Myostatin ... No safety concerns were identified in any active treatment groups. Conclusion: Combined administration of trevogrumab and garetosmab led to ...