Orforglipron for Pediatric Obesity

(ADVANCE Trial)

Recruiting at 46 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Weight reduction surgery, Type 1 diabetes, Thyroid carcinoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

125 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this pediatric, chronic weight management, Phase 3 Master Protocol (PWMP) is to create a framework to evaluate the safety and efficacy of pharmacologic agents for the treatment of obesity or overweight in pediatric participants.

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.

What data supports the effectiveness of the drug Orforglipron for pediatric obesity?

Research shows that Orforglipron, a drug similar to other GLP-1 receptor agonists, has been effective in helping adults with obesity lose weight. This suggests it might also help children with obesity, as similar drugs have shown positive effects in children. ^{1 2 3 4 5}

Is orforglipron safe for humans?

Orforglipron has been studied for safety in people with type 2 diabetes and obesity, showing it is generally safe for these conditions. However, specific safety data for pediatric obesity is not available from the studies mentioned. ^{2 3 4 5 6}

How is the drug orforglipron different from other treatments for pediatric obesity?

Orforglipron is unique because it is an oral, non-peptide drug that targets the GLP-1 receptor, which is different from many other obesity treatments that are injectable. This makes it potentially more convenient for children and adolescents who may prefer taking a pill over injections. ^{1 2 3 4 5}

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

Eligibility Criteria

This trial is for children with obesity or overweight issues. Specific details about who can join are not provided, but typically participants must meet certain health criteria and may need parental consent due to their age.

Inclusion Criteria

I am a teenager who is overweight with a health issue like high blood pressure or type 2 diabetes.

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

I tried and failed to lose enough weight with a diet and exercise program for 3 months.

Exclusion Criteria

I have type 1 diabetes or have had ketoacidosis or a hyperosmolar state.

Have HbA1c >9.0% (75 mmol/mol) as measured by central laboratory at screening

I or my family have a history of medullary thyroid cancer or MEN2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orforglipron or placebo orally for chronic weight management

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Orforglipron

Trial Overview The study is testing the safety and effectiveness of a drug called Orforglipron compared to a placebo (a substance with no active drug) in managing weight for obese or overweight kids as part of a larger program.

Participant Groups

Group I: Orforglipron (ISA PW01) Experimental Treatment 2 Interventions

Participants will receive orforglipron or placebo orally. Each ISA will detail the intervention specific.

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

Findings from Research

GLP-1 receptor agonists, such as exenatide and liraglutide, have been shown to safely and effectively reduce body weight and BMI in children and adolescents with obesity, based on a meta-analysis of 9 studies involving 574 participants.

While these medications improved glycemic control in children with insulin resistance and led to a modest decrease in systolic blood pressure, they also increased the risk of nausea, highlighting a common gastrointestinal side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis. Ryan, PM., Seltzer, S., Hayward, NE., et al.[2022]

In a 26-week phase 2 trial involving 383 participants with type 2 diabetes, orforglipron significantly reduced HbA1c levels by up to -2.10% compared to placebo and showed greater weight loss of up to -10.1 kg, indicating its efficacy as a treatment option.

The safety profile of orforglipron was comparable to other GLP-1 receptor agonists, with most adverse events being mild to moderate gastrointestinal issues, suggesting it may be a safer and more convenient alternative to injectable treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. Frias, JP., Hsia, S., Eyde, S., et al.[2023]

In a Phase 1b trial involving 68 participants with type 2 diabetes, orforglipron (LY3502970) demonstrated significant reductions in HbA1c levels (by -1.5% to -1.8%) and body weight (by -0.24 to -5.8 kg) compared to placebo, which only showed a -0.4% change in HbA1c.

Orforglipron was generally well tolerated, with gastrointestinal side effects similar to those seen with other GLP-1 receptor agonists, suggesting it may be a safe and effective oral alternative to injectable treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. Pratt, E., Ma, X., Liu, R., et al.[2023]

A study involving adults with obesity demonstrated that the daily oral GLP-1 receptor agonist orforglipron effectively aids in weight loss, showcasing its potential as a treatment option for obesity.

The findings suggest that orforglipron may offer a convenient oral alternative to traditional injectable GLP-1 receptor agonists, enhancing patient adherence to obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk. Lau, D.[2023]

In a phase 2 trial involving 272 adults with obesity, the oral GLP-1 receptor agonist orforglipron resulted in significant weight loss, with participants losing between 8.6% to 14.7% of their body weight by week 36, compared to only 2.3% in the placebo group.

Orforglipron was generally well-tolerated, with mild to moderate gastrointestinal side effects being the most common adverse events, leading to discontinuation in 10-17% of participants, similar to the safety profile of injectable GLP-1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. Wharton, S., Blevins, T., Connery, L., et al.[2023]

In a 12-week study involving 72 adults with type 2 diabetes, the multi-receptor agonist LY3437943 demonstrated a good safety profile, with gastrointestinal disorders being the most common side effects.

LY3437943 significantly reduced daily plasma glucose and HbA1c levels, as well as body weight, in a dose-dependent manner, supporting its potential for once-weekly dosing and further development in treating type 2 diabetes and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva, S., Coskun, T., Loh, MT., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. [2023]

6. England pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. [2022]