Orforglipron for Pediatric Obesity

(ADVANCE Trial)

Recruiting at 51 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Orforglipron (a GLP-1 receptor agonist) to determine its effectiveness in managing weight in young people. The goal is to assess the safety and efficacy of this medication for treating obesity or overweight conditions in children who have struggled to lose weight despite diet and exercise programs. It suits young participants who are significantly overweight and have health issues like high blood pressure, type 2 diabetes, or sleep apnea. Participants should not have had or be planning any weight-loss surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for obesity.

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 Orforglipron is likely to be safe for pediatric participants?

Research has shown that orforglipron, a pill for weight management, is as safe as current injectable treatments. Studies involving adults with diabetes and obesity have found orforglipron to be generally well-tolerated. Although these studies are ongoing, results so far indicate that orforglipron does not cause major side effects that would halt its development. This suggests potential safety for children, based on its use in adults. However, since orforglipron is a new treatment, the trial will carefully monitor its safety in children. ^{1 2 3 4 5}

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

Unlike the standard treatments for pediatric obesity, which often include lifestyle changes and medications like orlistat, Orforglipron is an oral medication that targets the body's GLP-1 receptors. This action mimics a hormone that helps control appetite and blood sugar levels. Researchers are excited about Orforglipron because it offers a potentially more targeted and convenient approach by being taken orally, as opposed to the injectable forms of current GLP-1 receptor agonists. This could make it easier for young patients to stick with their treatment plan and see results.

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

Research has shown that orforglipron, a pill that helps control blood sugar and appetite, offers promising results for treating obesity. In earlier studies, many patients taking orforglipron lost a significant amount of weight. Specifically, 54.6% of patients lost 10% or more of their body weight, and 36.0% lost 15% or more. These results suggest that orforglipron could be effective for individuals struggling with obesity. The treatment also lowered A1C levels, which measure blood sugar control, by an average of 1.3% to 1.6%. These findings support the potential of orforglipron for weight management in children and teens. Participants in this trial will receive orforglipron or a placebo to further evaluate its effectiveness in pediatric obesity. ^{1 3 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 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

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.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40960239/

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ... Among the patients in the orforglipron 36-mg group, 54.6% had a reduction of 10% or more, 36.0% had a reduction of 15% or more, and 18.4% had a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06672939?term=LY3549492+OR+orforglipron

A Study of Orforglipron (LY3502970) in Adolescent ... The age groups are: Child (birth-17); Adult (18-64); Older Adult (65+) ... A measure of all deaths, due to any cause, that occur during a clinical study. ... A ...

3. science.org science.org/doi/10.1126/scitranslmed.adp5765

The pharmacological basis for nonpeptide agonism of ... Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

4. trials.lilly.com trials.lilly.com/en-US/trial/551535

A Study of Orforglipron (LY3502970) in Adolescent ... The main purpose of this study, performed under Master Protocol J4M-MC-PWMP, is to evaluate the efficacy, safety, and pharmacokinetics of orforglipron once ...

5. investor.lilly.com investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically

Lilly's oral GLP-1, orforglipron, demonstrated statistically ... Orforglipron is the first small molecule GLP-1 to successfully complete a Phase 3 trial, lowering A1C by an average of 1.3% to 1.6% across doses.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37344954/

Orforglipron (LY3502970), a novel, oral non-peptide ... ... Orforglipron had a pharmacodynamic and safety profile similar to that of injectable GLP-1RAs, which supports continued clinical development.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05869903

NCT05869903 | A Study of Orforglipron (LY3502970) in ... This study will investigate the efficacy and safety of once daily oral orforglipron in adult participants with obesity or overweight with weight-related ...

8. invivochem.com invivochem.com/glp-1-receptor-agonist-1.html

Orforglipron (LY3502970; GLP-1 receptor agonist 1) "ACHIEVE-1 is the first of seven Phase 3 studies examining the safety and efficacy of orforglipron across people with diabetes and obesity. We are pleased to ...