Tirzepatide + Mibavademab for Obesity

Not currently recruiting at 33 trial locations

Overseen By Elly R Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Thyroid carcinoma, Hepatitis, others

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

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two treatments, tirzepatide (a GIP/GLP-1 receptor agonist) and mibavademab (an experimental treatment), can lead to greater weight loss compared to using tirzepatide alone. The trial lasts about 74 weeks and includes several treatment groups to assess different combinations and durations of these treatments. Suitable candidates for this trial have obesity (BMI between 30 and 40) and do not have diabetes. Participants must be willing to learn how to self-inject the treatments or have assistance from someone trained to do so. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in obesity treatment.

Do I need to stop my current medications for this trial?

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

Will I have to stop taking my current medications?

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

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

Research shows that tirzepatide is usually well-tolerated. Common side effects include nausea and vomiting, typical for medications that aid in weight and diabetes management.

Less information exists about the safety of mibavademab in humans. As this study is in the early stages, researchers are still collecting safety data for mibavademab. They are testing the combination of tirzepatide and mibavademab to determine if it leads to better weight loss than tirzepatide alone.

For those considering joining the trial, it may be reassuring to know that tirzepatide has been well-studied. However, the new combination with mibavademab is still under evaluation for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tirzepatide and mibavademab for obesity because it offers a potentially novel approach to weight management. Unlike standard treatments, which often include lifestyle changes, medications like orlistat, or GLP-1 receptor agonists such as semaglutide, tirzepatide is a dual agonist that targets both GIP and GLP-1 receptors, which may enhance weight loss effects. Mibavademab is an investigational antibody that could have a complementary mechanism by affecting different pathways involved in obesity. This combination might not only improve weight loss outcomes but also offer a new option for patients who have not achieved desired results with existing therapies.

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

Research has shown that tirzepatide alone has led to significant weight loss in previous studies. This treatment reduces appetite and controls blood sugar levels, aiding in weight loss. In this trial, researchers are testing whether combining tirzepatide with mibavademab can lead to even greater weight loss. Participants in different arms of the trial will receive various combinations of tirzepatide and mibavademab, or their placebos, to evaluate the effectiveness of these treatments. Early results suggest that adding mibavademab might enhance the effects of tirzepatide. Although limited data from human studies exist on this combination, the approach appears promising based on current knowledge of each drug. ^{1 2 4 5 6}

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 who are looking to lose weight. Participants should be committed to the study duration of about 72 weeks and up to 19 visits. Specific eligibility criteria details were not provided, so interested individuals should inquire further.

Inclusion Criteria

Have a body mass index (BMI) of ≥30 kg/m2 and ≤40 kg/m2

I am willing to learn or have someone to help with self-injections for the study.

I am using birth control as required by local laws for clinical study participants.

Exclusion Criteria

I have hepatitis.

I have diabetes (Type 1 or Type 2) or have had severe diabetes complications.

Have a self-reported change (increase or decrease) in body weight >5 kg within 3 months prior to screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide and mibavademab or placebo for 24 weeks

24 weeks

Up to 19 visits in total

Extended Treatment

Participants continue with tirzepatide and mibavademab or placebo for an additional 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mibavademab
• Tirzepatide

Trial Overview The study is testing whether a combination of two drugs, Tirzepatide and Mibavademab, leads to more weight loss compared to just Tirzepatide alone in obese adults over approximately a year and a half.

How Is the Trial Designed?

Group I: Tirzepatide (TZP) + Mibavademab (MIBA) [Group A] Experimental Treatment 2 Interventions

Participants will receive TZP subcutaneously (SC) and MIBA for 24 weeks. Participants in Group A will be randomized (Randomization 2) to groups C and D at week 24.

Group II: TZP + Mibavademab-placebo (MIBA-PBO) [Group B] Experimental Treatment 2 Interventions

Participants will receive TZP SC and MIBA-PBO SC for 24 weeks. Participants in Group B will be randomized (Randomization 2) to Groups E, F, G, and H at week 24.

Group III: TZP + MIBA-PBO then TZP-PBO + MIBA-PBO [Group H] Experimental Treatment 3 Interventions

Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP-PBO SC + MIBA-PBO SC for 24 weeks.

Group IV: TZP + MIBA-PBO then TZP-PBO + MIBA [Group F] Experimental Treatment 4 Interventions

Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP-PBO SC + MIBA SC for 24 weeks.

Group V: TZP + MIBA-PBO then TZP + MIBA [Group G] Experimental Treatment 3 Interventions

Participants will receive TZP SC + MIBA-PBO SC for 24 weeks followed by TZP SC + MIBA SC for 24 weeks.

Group VI: TZP + MIBA-PBO [Group E] Experimental Treatment 2 Interventions

Participants will receive TZP SC + MIBA-PBO SC for 48 weeks.

Group VII: TZP + MIBA then Tirzepatide-placebo (TZP-PBO) + MIBA [Group C] Experimental Treatment 3 Interventions

Participants will receive TZP SC and MIBA SC for 24 weeks followed by TZP-PBO SC and MIBA SC for 24 weeks.

Group VIII: TZP + MIBA [Group D] Experimental Treatment 2 Interventions

Participants will receive TZP SC + MIBA SC for 48 weeks.

Tirzepatide is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

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

Regeneron Pharmaceuticals

Industry 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 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]

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]

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]

Tirzepatide, a once-weekly medication for type 2 diabetes, not only improves blood sugar control but also leads to significant weight loss and positive changes in cardiovascular health, such as reduced blood pressure and improved insulin sensitivity.

The weight loss and metabolic benefits of tirzepatide are linked to its dual action as a GIP and GLP-1 receptor agonist, suggesting that these mechanisms play a crucial role in its effectiveness for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. Várkonyi, TT., Pósa, A., Pávó, N., et al.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

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 GLP-1/GIP receptor co-agonist, has been shown to significantly reduce glycosylated hemoglobin levels (1.87% to 3.02%) and body weight (5.4 to 12.9 kg) in people with type 2 diabetes over treatment periods of up to 104 weeks, demonstrating its efficacy compared to placebo and other diabetes medications.

In individuals without diabetes, tirzepatide also led to substantial weight loss (16.5% to 22.4%) over 72 weeks, indicating its potential for obesity management as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Sinha, R., Papamargaritis, D., Sargeant, JA., et al.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

Tirzepatide (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06373146

NCT06373146 | A Study of Tirzepatide (LY3298176) Plus ... The main purpose of this study is to determine if combining tirzepatide with mibavademab will result in more weight loss in adult participants than ...

2. trials.lilly.com trials.lilly.com/en-US/trial/477977

A Study of Tirzepatide (LY3298176) Plus Mibavademab ... The main purpose of this study is to determine if combining tirzepatide with the mibavademab will result in more weight loss in adult participants than ...

3. synapse.patsnap.com synapse.patsnap.com/article/what-clinical-trials-have-been-conducted-for-mibavademab

What clinical trials have been conducted for Mibavademab? This trial is a phase 2, randomized, double-blind, placebo-controlled, proof-of-concept study designed to evaluate the efficacy of combining ...

4. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy0000001AILEA2/nct06373146

A Study of Tirzepatide (LY3298176) Plus Mibavademab ... The main purpose of this study is to determine if combining tirzepatide with mibavademab will result in more weight loss in adult participants than tirzepatide ...

5. withpower.com withpower.com/trial/phase-2-obesity-4-2024-1346f

Tirzepatide + Mibavademab for Obesity · Info for Participants It helps with weight loss and improves health outcomes by reducing appetite and controlling blood sugar levels. It has shown good results in clinical trials for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12304053/

Triple Agonism Based Therapies for Obesity - PMC A comprehensive phase 3 program is ongoing to evaluate efficacy, safety, and cardiovascular/renal outcomes in people with obesity and/or T2D.