Bimagrumab + Tirzepatide for Obesity

Not currently recruiting at 13 trial locations

Overseen By Bonnie Kimmel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must not be taking: Metformin, Glucose-lowering

Disqualifiers: Diabetes, Hypertension, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of two medications, Bimagrumab and Tirzepatide, for treating obesity. The study explores how these medications work separately and together to assist individuals with obesity or those who are overweight and have at least one related health issue, such as high blood pressure or sleep apnea. Participants should not have Type 2 Diabetes and must have maintained a stable weight for the last three months. The trial lasts about 70 weeks, providing a thorough examination of how these treatments could help manage weight-related health concerns. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in obesity treatment.

Will I have to stop taking my current medications?

The trial requires that you do not take metformin or any other glucose-lowering medications. Additionally, you should not be taking medications that may cause significant weight gain or promote weight loss within 3 months before the trial.

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

Research has shown that bimagrumab is generally safe. In one study, participants used it for 48 weeks and tolerated it well, experiencing few side effects while losing body fat. This suggests it usually works without many issues for most people.

Tirzepatide has also been studied for weight loss. It effectively aids weight loss, though some experience side effects, often related to the stomach, such as nausea. Serious side effects are rare.

Since this trial is in an early stage, it primarily focuses on assessing the safety of these treatments. Researchers continue to closely monitor side effects. Both bimagrumab and tirzepatide have shown promise in earlier research, but more information is needed to confirm their long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bimagrumab and Tirzepatide for obesity because these treatments offer unique approaches compared to current options. Unlike most obesity treatments that primarily focus on appetite suppression or calorie absorption, Bimagrumab works by targeting the activin type II receptor, which helps increase muscle mass and reduce fat. Tirzepatide, on the other hand, is a dual agonist that activates both GIP and GLP-1 receptors, potentially offering improved blood sugar control and weight loss. This combination could offer a more comprehensive solution by simultaneously reducing fat and enhancing muscle, setting it apart from other treatments that typically address only one of these aspects.

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

Research has shown that bimagrumab can reduce body fat while increasing muscle, aiding in weight management by helping people lose fat but retain muscle. In this trial, some participants will receive bimagrumab alone. Studies have also found that tirzepatide can lead to significant weight loss, with some individuals losing over 20% of their body weight. Other participants in this trial will receive tirzepatide alone. Both treatments aim to help manage obesity effectively, and when used together in certain trial arms, they may offer even greater benefits. ^{2 3 5 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with obesity or overweight who also have at least one weight-related health issue but do not have Type 2 Diabetes. The study will last approximately 54 weeks.

Inclusion Criteria

My BMI is over 27 and I have a weight-related health issue.

My weight has been stable, with less than a 5% change, for the last 3 months.

Exclusion Criteria

At least one laboratory value suggestive of diabetes during screening

I have a history of frequent or ongoing fast heart rhythms.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Bimagrumab and/or Tirzepatide, or placebo, subcutaneously for weight management

54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bimagrumab
• Tirzepatide

Trial Overview The effectiveness and safety of two medications, Bimagrumab and Tirzepatide, are being tested. They can be given alone or together to see how well they help with weight management in obese or overweight individuals.

How Is the Trial Designed?

Group I: Part B: Bimagrumab Dose 2 (slow titration) + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group II: Part B: Bimagrumab Dose 2 (no titration) + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group III: Part B: Bimagrumab Dose 2 (fast titration) + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group IV: Part B: Bimagrumab Dose 1 + Tirzepatide Placebo Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide placebo SC

Group V: Part A: Bimagrumab Dose 2 + Tirzepatide Placebo Experimental Treatment 2 Interventions

Participants will receive bimagrumab subcutaneously (SC) and tirzepatide placebo SC

Group VI: Part A: Bimagrumab Dose 2 + Tirzepatide Dose 2 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group VII: Part A: Bimagrumab Dose 1 + Tirzepatide Dose 2 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group VIII: Part A: Bimagrumab Dose 1 + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC

Group IX: Part A: Bimagrumab Placebo + Tirzepatide Dose 1 Active Control 2 Interventions

Participants will receive bimagrumab placebo SC and tirzepatide SC

Group X: Part A: Bimagrumab Placebo + Tirzepatide Dose 2 Active Control 2 Interventions

Participants will receive bimagrumab placebo SC and tirzepatide SC

Group XI: Part A: Bimagrumab Placebo + Tirzepatide Placebo Placebo Group 2 Interventions

Participants will receive bimagrumab placebo SC and tirzepatide placebo SC

Group XII: Part B: Bimagrumab Placebo + Tirzepatide Placebo Placebo Group 2 Interventions

Participants will receive bimagrumab placebo SC and tirzepatide placebo SC

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase I study involving 32 patients with advanced solid tumors, the combination of ociperlimab and tislelizumab was well tolerated, with no dose-limiting toxicities reported and a recommended phase II dose established at ociperlimab 900 mg plus tislelizumab 200 mg every 3 weeks.

Preliminary results showed an overall response rate of 10% and a disease control rate of 50%, indicating some antitumor activity, which supports further investigation in phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. Frentzas, S., Kao, S., Gao, R., et al.[2023]

The combination of nivolumab, an immune checkpoint inhibitor, and metformin, an oral diabetes medication, was found to be safe for use in 40 diabetic cancer patients, with 75% experiencing mild adverse events like fatigue and rash, and only 20% experiencing more severe side effects.

Higher doses of metformin (over 1,000 mg daily) were associated with significantly improved progression-free survival and overall survival rates, suggesting a potential synergistic antitumor effect when combined with nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Nivolumab and Metformin in Diabetic Cancer Patients: Is It Safe and More Active? Ciccarese, C., Iacovelli, R., Buti, S., et al.[2022]

The SURMOUNT 2 trial demonstrated that tirzepatide, a GIPR:GLP-1R co-agonist, shows unprecedented weight loss efficacy in patients with obesity and type 2 diabetes, suggesting a significant advancement in anti-obesity treatments.

This trial highlights the potential of tirzepatide to achieve weight loss results that were previously thought to be nearly impossible, marking a new era in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SURMOUNTing body weight barriers in type 2 diabetes. Novikoff, A., Müller, TD.[2023]

LY3298176, a dual GIP and GLP-1 receptor agonist, demonstrated significant improvements in glycemic control and body weight reduction in both preclinical studies and a Phase 1b trial involving 142 subjects with type 2 diabetes mellitus (T2DM).

The most common side effects were mild to moderate gastrointestinal issues, which were dose-dependent, indicating that while LY3298176 is effective, monitoring for these side effects is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Coskun, T., Sloop, KW., Loghin, C., et al.[2021]

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

The combination of mogamulizumab and nivolumab was found to be safe and tolerable in a study involving 114 patients with advanced solid tumors, with no dose-limiting toxicities observed during the treatment.

While the treatment showed an objective response rate of 10.5% and a disease control rate of 36.8%, it did not demonstrate enhanced efficacy compared to existing treatments, with median overall survival of 9.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors. Hong, DS., Rixe, O., Chiu, VK., et al.[2023]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

Liraglutide and semaglutide, GLP-1 receptor mimetics, have been approved for weight management in obese individuals, showing promising results in Phase III clinical trials.

Tirzepatide, a GLP-1R and GIPR co-agonist, has received Fast Track designation for obesity management and may offer fewer side effects, suggesting it could be a more sustainable option for long-term weight management compared to existing GLP-1R mimetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy. Lafferty, RA., Flatt, PR., Irwin, N.[2023]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed greater improvements in glucose control and weight loss compared to the GLP-1 receptor agonist dulaglutide in a study involving 316 participants with type 2 diabetes.

The improvements in insulin sensitivity and beta-cell function with tirzepatide were only partially linked to weight loss, indicating that its dual receptor action provides unique mechanisms for better glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. Thomas, MK., Nikooienejad, A., Bray, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06901349

NCT06901349 | A Study of Bimagrumab (LY3985863) and ... The main purpose of this study is to see how well and how safely bimagrumab, tirzepatide, and the combination, work in lowering body weight in participants ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2774903

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... Those who received bimagrumab had a significantly larger decrease in total body fat mas and glycated hemoglobin and increase in lean mass compared with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7807292/

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... Those who received bimagrumab had a significantly larger decrease in total body fat mas and glycated hemoglobin and increase in lean mass compared with ...

4. adameetingnews.org adameetingnews.org/believe-spotlights-quality-and-quantity-approach-to-weight-management-with-combo-therapy/

BELIEVE spotlights quality and quantity approach to weight ... The phase 2 BELIEVE trial showed that the addition of bimagrumab, an activin type II receptor-targeted antibody that promotes muscle ...

5. biospace.com biospace.com/drug-development/lilly-cuts-mid-stage-obesity-study-of-muscle-sparing-antibody

Lilly Cuts Mid-Stage Obesity Study of Muscle-Sparing ... In June, Lilly released Phase IIb data showing that bimagrumab indeed helped maintain muscle mass in patients undergoing treatment with Novo ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05616013

NCT05616013 | Safety and Efficacy of Bimagrumab and ... Key Inclusion Criteria: A written informed consent must be obtained before any study-related assessments are performed.

7. trials.lilly.com trials.lilly.com/en-US/trial/546217

A Study to Investigate Weight Management With Bimagrumab ... The main purpose of this study is to evaluate the efficacy and safety of Bimagrumab and Tirzepatide, alone or in combination, in adults with obesity or ...