Tirzepatide for Pediatric Obesity

No longer recruiting at 2 trial locations

Overseen By Carl Griffin, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Pancreatitis, Obesity surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on evaluating the safety and tolerability of tirzepatide, a potential new drug for weight management, in children with obesity. Researchers aim to understand how the body processes this medicine and identify any side effects. Participants will receive either tirzepatide or a placebo to compare outcomes. Eligible children have a body mass index (BMI) above the 95th percentile for their age and gender and have not succeeded in losing weight through lifestyle changes. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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 tirzepatide is likely to be safe for humans?

Research shows that tirzepatide is generally safe and well-tolerated. In previous studies, most participants handled it well. These large, long-term studies found tirzepatide to be mostly safe.

Some participants experienced side effects, with nausea and diarrhea being the most common. These side effects were usually mild or moderate, and serious side effects were rare.

The FDA has already approved tirzepatide for treating type 2 diabetes in adults, indicating its safety for adults. However, this trial aims to determine its safety for children with obesity. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Tirzepatide is unique because it combines the actions of two hormones, GLP-1 and GIP, which help regulate blood sugar and appetite. Current treatments for pediatric obesity often focus solely on diet and exercise or medications that target only one hormone. Unlike these options, tirzepatide's dual-action mechanism may enhance weight loss and improve metabolic health more effectively. Researchers are excited because this approach could lead to more significant and sustainable weight loss in children, potentially transforming the standard care for pediatric obesity.

What evidence suggests that tirzepatide might be an effective treatment for pediatric obesity?

Research has shown that tirzepatide, which participants in this trial may receive, effectively aids in weight loss. In studies, participants taking tirzepatide lost a significant amount of weight, with some losing up to 22.9% of their body weight over about 3.5 years. It outperformed similar treatments, such as certain other medications, in promoting weight loss and enhancing insulin use in the body. These findings suggest that tirzepatide could be a promising option for managing obesity. ^{1 4 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 children with obesity, defined as having a BMI ≥ the 95th percentile for their age and sex. They should have tried losing weight through lifestyle changes without success. Girls must be in early puberty (Tanner Stage 1). It's not for those with certain medical conditions like pancreatitis, other causes of obesity, diabetes, or significant recent weight change.

Inclusion Criteria

Have failed to achieve adequate weight loss through lifestyle modification in the investigator's opinion

I am a female and have not started puberty.

My BMI is in the top 5% for my age and sex.

Exclusion Criteria

My obesity is caused by a hormonal disorder or a specific genetic condition.

I don't have major health issues that could affect drug processing or pose risks with the study drug.

Change in body weight above 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide or placebo subcutaneously to evaluate safety and tolerability

13 weeks

Weekly visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tirzepatide

Trial Overview The study tests Tirzepatide (LY3298176) against a placebo to see how safe it is and how well kids tolerate it. Researchers will also check how the body handles this drug over about 13 weeks, excluding screening time.

How Is the Trial Designed?

Group I: Cohort 3: 2.5-5 mg Tirzepatide (BW 40 to 60 kg) Experimental Treatment 1 Intervention

Participants in this cohort had a screening body weight between 40 to 60 kg, inclusive, received 2.5 mg tirzepatide administered SC QW during Weeks 1 to 4 followed by 5 mg tirzepatide during Weeks 5 to 8.

Group II: Cohort 2: 1.25-2.5 mg Tirzepatide (BW <50 kg) Experimental Treatment 1 Intervention

Participants in this cohort had a screening body weight less than 50 kg received 1.25 mg tirzepatide administered SC QW during Weeks 1 to 4 followed by 2.5 mg tirzepatide during Weeks 5 to 8.

Group III: Cohort 1: 2.5-5 mg Tirzepatide (BW >=50 kg) Experimental Treatment 1 Intervention

Participants in this cohort had a screening body weight of at least 50 kg received 2.5 milligrams (mg) tirzepatide administered SC QW during Weeks 1 to 4 followed by 5 mg tirzepatide during Weeks 5 to 8.

Group IV: Cohort 1: Placebo (BW >=50 kg) Placebo Group 1 Intervention

Participants in this cohort had a screening body weight (BW) of at least 50 kilograms (kg) received placebo administered subcutaneously (SC) once weekly (QW) during Weeks 1 to 8.

Group V: Cohort 2: Placebo (BW <50 kg) Placebo Group 1 Intervention

Participants in this cohort had a screening body weight less than 50 kg received placebo administered SC QW during Weeks 1 to 8.

Group VI: Cohort 3: Placebo (BW 40 to 60 kg) Placebo Group 1 Intervention

Participants in this cohort had a screening body weight between 40 to 60 kg, inclusive, received placebo administered SC QW during Weeks 1 to 8.

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

Published Research Related to This Trial

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 medication for type 2 diabetes, shows a dose-dependent increase in gastrointestinal adverse events (AEs), with nausea and diarrhea being the most common, affecting up to 49% of participants at the highest dose (15 mg).

Despite the gastrointestinal side effects, serious adverse events like severe hypoglycemia and acute pancreatitis are rare (≤ 1%), indicating that tirzepatide is generally safe for use in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. Mishra, R., Raj, R., Elshimy, G., et al.[2023]

Zavegepant, a newly approved intranasal gepant, represents a significant advancement in migraine treatment by antagonizing the CGRP receptor, which is linked to chronic migraine conditions.

Unlike earlier gepants, zavegepant and other recent oral gepants like rimegepant and ubrogepant have been approved without warnings for hepatotoxicity, suggesting a potentially safer profile, although long-term safety and efficacy data are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focus on zavegepant: the first intranasal third-generation gepant. Scuteri, D., Tarsitano, A., Tonin, P., et al.[2022]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed significant reductions in Hemoglobin A1c levels (up to 3.02%) and weight loss in adults with uncontrolled type 2 diabetes, outperforming both placebo and active comparators like semaglutide.

The safety profile of tirzepatide was comparable to semaglutide regarding gastrointestinal adverse effects, and it did not increase the incidence of major cardiovascular events compared to insulin glargine, indicating it may be a valuable addition to diabetes treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. Bradley, CL., McMillin, SM., Hwang, AY., 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]

CGRP antagonists, including second-generation gepants like rimegepant and ubrogepant, have been shown to be effective for both acute and preventive treatment of migraines, with no increased mortality risks associated with their use.

While serious adverse events were reported, they were likely unrelated to the medications, indicating a favorable safety profile; however, ongoing monitoring for long-term side effects, particularly in elderly populations, is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gepants for Acute and Preventive Migraine Treatment: A Narrative Review. Rissardo, JP., Caprara, ALF.[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]

Gepants, a new class of migraine treatments including ubrogepant, atogepant, rimegepant, and zavegepant, have been shown to be effective and safe for both acute and preventive therapy of migraines, with various administration routes (oral and intranasal).

Current literature suggests that while gepants are well-tolerated and effective, it is still unclear if they will outperform existing migraine treatments like triptans and monoclonal antibodies in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacotherapeutic management of episodic and chronic migraine with gepants. Tajti, J., Szok, D., Csáti, A., et al.[2023]

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]

Migraine is a prevalent issue among children and adolescents, leading to significant disability, yet there are limited evidence-based treatment options compared to adults.

This review highlights the need for evaluating newer migraine therapies, such as onabotulinumtoxinA and CGRP monoclonal antibodies, in pediatric populations, as current treatments do not work for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the Guidelines: A Narrative Review of Treatments on the Horizon for Migraine in Children and Adolescents. VanderPluym, JH., Victorio, MCC., Oakley, CB., 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2416394

Tirzepatide as Compared with Semaglutide for ... Clinically meaningful weight reductions occur with both medications, with reported mean weight reductions of up to 22.9% after nearly 3.5 years ...

2. investor.lilly.com investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist ... Mounjaro met the primary objective of non-inferiority vs. Trulicity with an 8% lower rate of MACE-3 events, while delivering greater ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12313391/

Weight Loss Efficacy of Tirzepatide Compared to Placebo or ... The secondary outcomes included safety profiles and achievement of categorical weight loss of 5%, 10% and 15%. We performed the statistical analysis on RevMan ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822209

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... Subsequent clinical trials confirmed that tirzepatide was more effective than selective GLP-1 agonists in increasing insulin secretion and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05822830

NCT05822830 | A Study of Tirzepatide (LY3298176) in ... The main purpose of this phase 3b study is to evaluate the efficacy and safety of tirzepatide compared with semaglutide in adult participants who have obesity ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39536238/

Tirzepatide for Obesity Treatment and Diabetes Prevention Results: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, - ...

7. prnewswire.com prnewswire.com/news-releases/lillys-mounjaro-tirzepatide-a-gipglp-1-dual-receptor-agonist-reduced-a1c-by-an-average-of-2-2-in-a-phase-3-trial-of-children-and-adolescents-with-type-2-diabetes-302559576.html

Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual receptor ... The 10 mg dose of Mounjaro reduced BMI by 11.2% on average at 30 weeks. Improvements in A1C and BMI reductions continued through 52 weeks in the ...