Bimagrumab + Tirzepatide for Healthy Subjects

Overseen By This is a single site clinical trial 1-877-CTLILLY (1-877-285-4559) or

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Pancreatitis, Hepatitis, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different forms of bimagrumab, a muscle-targeting drug, alone or with tirzepatide, a medication for blood sugar control, behave in the body. The study tests various combinations of these treatments to better understand their effects. Researchers seek healthy individuals with a BMI between 22 and 30 who have not experienced major weight changes or used weight loss medications recently. Participants will help determine potential future uses for these treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have taken weight loss medications or remedies in the past 3 months.

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

Research has shown that bimagrumab is generally safe and well-tolerated. In studies, most participants taking bimagrumab reported only mild side effects, such as diarrhea and muscle spasms. These side effects were not serious and were similar across different groups, including older and overweight adults.

Early studies indicate that the combination of bimagrumab and tirzepatide is safe, as it did not lead to serious side effects. Notably, this combination caused fewer liver-related issues compared to other drug combinations.

Overall, both treatments appear safe based on current studies. However, since this is an early-phase trial, the focus is primarily on checking safety and dosage, so there might still be more to learn. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using bimagrumab and tirzepatide together because this combination could offer a novel approach to treating metabolic conditions like obesity and type 2 diabetes. Bimagrumab is unique because it is a monoclonal antibody that targets the activin type II receptor, which helps increase muscle mass while reducing fat. Tirzepatide, on the other hand, mimics hormones that regulate insulin and appetite, offering dual benefits for blood sugar control and weight loss. By combining these two, the treatment aims to tackle both muscle growth and fat reduction simultaneously, which is not a feature of most current options like metformin or GLP-1 receptor agonists. This dual-action potential is what makes researchers hopeful about its impact.

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

Research has shown that bimagrumab can help reduce body fat and increase muscle. One study found that participants using bimagrumab lost about 6.5% of their body weight due to these changes, indicating its potential usefulness for managing weight. In this trial, some participants will receive bimagrumab alone, while others will receive it in combination with tirzepatide. This combination might further lower body weight. Early studies are exploring how these drugs work together to improve body composition. ^{2 4 6 7 8}

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 healthy individuals with a BMI of 22.0 to 30.0 kg/m2 who haven't had significant weight changes or taken weight loss remedies in the last 3 months. They shouldn't have a history of pancreatitis, hepatitis, or uncontrolled high blood pressure.

Inclusion Criteria

Are considered healthy as determined by medical evaluation including medical history and physical examination

Have a body mass index (BMI) within the range of 22.0 to 30.0 kilograms per square meter (kg/m2), inclusive

Exclusion Criteria

Have a self-reported increase or decrease in body weight, greater than 5 kilograms (kg), within 3 months prior to screening

I have or had pancreatitis or hepatitis.

I have used weight loss medications or remedies in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bimagrumab alone or with tirzepatide for 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bimagrumab
• Tirzepatide

Trial Overview The study tests how bimagrumab alone and combined with tirzepatide affects the body's concentration levels over approximately 4.5 months, including screening and follow-up phases.

How Is the Trial Designed?

Group I: Bimagrumab Dose 2 Test Material + Tirzepatide (Coformulation) Experimental Treatment 1 Intervention

Participants will receive bimagrumab with tirzepatide SC for 4 weeks

Group II: Bimagrumab Dose 2 Test Material + Tirzepatide (Coadministration) Experimental Treatment 2 Interventions

Participants will receive bimagrumab SC and tirzepatide SC for 4 weeks

Group III: Bimagrumab Dose 1 Test Material + Tirzepatide (Coformulation) Experimental Treatment 1 Intervention

Participants will receive a single dose of bimagrumab with tirzepatide SC

Group IV: Bimagrumab Dose 1 Test Material + Tirzepatide (Coadministration) Experimental Treatment 2 Interventions

Participants will receive a single dose of bimagrumab SC and a single dose of tirzepatide SC

Group V: Bimagrumab Dose 1 Reference Material Experimental Treatment 1 Intervention

Participants will receive a single dose of bimagrumab subcutaneously (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 the CITYSCAPE trial involving 275 patients with chemotherapy-naive, PD-L1-positive non-small-cell lung cancer, the combination of tiragolumab and atezolizumab resulted in a significantly higher objective response rate (31.3% vs. 16.2%) and improved median progression-free survival (5.4 months vs. 3.6 months) compared to placebo plus atezolizumab.

The safety profile of tiragolumab plus atezolizumab was generally similar to that of atezolizumab alone, with serious treatment-related adverse events occurring in 21% of patients in the combination group, indicating that this combination therapy is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Cho, BC., Abreu, DR., Hussein, M., et al.[2022]

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]

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [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]

Citations

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

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... The combined loss in total body FM and gain in lean mass led to a net 6.5% reduction in body weight in patients receiving bimagrumab compared ...

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

Effect of Bimagrumab vs Placebo on Body Fat Mass Among ... A single intravenous dose of bimagrumab in human participants not only increased lean mass but significantly reduced total body fat mass (FM) and improved ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05616013

NCT05616013 | Safety and Efficacy of Bimagrumab and ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

4. link.springer.com link.springer.com/article/10.1007/s40520-024-02825-4

Effect of Bimagrumab on body composition: a systematic ... Eligible studies reported outcomes related to either body composition, such as thigh muscle volume, fat-free body mass, or fat body mass, or ...

5. journals.lww.com journals.lww.com/10.1097/CRD.0000000000001113

Bimagrumab: Novel Medical Therapy for Inclusion Body... It has improved muscle mass in patients with sarcopenia and posthip fracture recovery, while only showing minimal improvements in mobility and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7749589/

Safety and pharmacokinetics of bimagrumab in healthy ... Bimagrumab was safe and well tolerated and demonstrated similar PK in older and obese adults. A single dose of bimagrumab rapidly increased TMV and LBM and ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000010417

Long-term safety and tolerability of bimagrumab (BYM338) ... Long-term treatment up to 2 years with bimagrumab had a good safety profile and was well tolerated in individuals with sIBM. An increase in muscle mass was ...

8. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(19)30200-5/abstract

Safety and efficacy of intravenous bimagrumab in ... The most frequently reported adverse events with bimagrumab were muscle spasms (32 [51%] in the bimagrumab 10 mg/kg group, 43 [68%] in the 3 mg/kg group, 25 [40 ...