A Study of Orforglipron (LY3502970) in Adolescent Participants With Obesity, or Overweight With Related Comorbidities

Official title

Efficacy, Safety, and Pharmacokinetics of Orforglipron Once Daily Oral Versus Placebo in Adolescent Participants Who Have Obesity, or Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind Trial (ADVANCE-ATTAIN-ADOLESCENTS)

Overview

The main purpose of this study, performed under Master Protocol J4M-MC-PWMP (NCT06672549), is to evaluate the efficacy, safety, and pharmacokinetics of orforglipron once daily oral versus Placebo in adolescent participants with obesity, or overweight with related comorbidities. Participation in the study will last about 18 months. Participants who have completed the primary PW01 study (including the 4-week safety follow-up period) will have the opportunity to receive an additional 156 weeks of treatment with orforglipron as well as continuing the lifestyle intervention.

Interventions

• Drug Orforglipron
  Administered orally
• Drug Placebo
  Administered orally

Primary outcome measures

• Percent Change from Baseline in Body Mass Index (BMI) [Time frame: Baseline, Week 72]

Secondary outcome measures (12)

• Change from Baseline in BMI [Time frame: Baseline, Week 72]
• Change from Baseline in Body Weight [Time frame: Baseline, Week 72]
• Change from Baseline in Waist Circumference [Time frame: Baseline, Week 72]
• Change from Baseline in Body Weight Percentile [Time frame: Baseline, Week 72]
• Change in Impact of Weight on Quality of Life (IWQOL)-Kids Total and Domain Scores [Time frame: Baseline, Week 72]
• Change from Baseline in Systolic Blood Pressure [Time frame: Baseline, Week 72]
• Change from Baseline in Diastolic Blood Pressure [Time frame: Baseline, Week 72]
• Percent Change from Baseline in Total Cholesterol [Time frame: Baseline, Week 72]
• Change from Baseline in Fasting Glucose [Time frame: Baseline, Week 72]
• Percent Change from Baseline in Fasting Insulin [Time frame: Baseline, Week 72]
• Percent Change from Baseline in Total Body Fat Mass as Determined by Dual-Energy X-Ray Absorptiometry (DXA) [Time frame: Baseline, Week 72]
• Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Orforglipron [Time frame: Baseline, Week 72]

Eligibility criteria

Inclusion criteria

J4M-MC-PWMP

• Have a history of at least 1 unsuccessful effort to lose sufficient body weight after participation in a structured lifestyle modification program (diet and exercise counseling for at least 3 months) prior to screening.
• Obesity as defined by BMI equal to or above the 95th percentile for age and sex (on age- and gender-specific growth chart \[CDC-NCHS, 2022\]); OR
• Overweight as defined by BMI equal to or above the 85th percentile but less than the 95th percentile for age and sex, on age- and sex-specific growth chart (CDC-NCHS, 2022), and at least 1 weight-related comorbidity,

• hypertension
• type 2 diabetes (T2D)
• prediabetes
• dyslipidemia
• obstructive sleep apnea
• metabolic dysfunction-associated steatohepatitis (MASH) or metabolic dysfunction-associated steatotic liver disease (MASLD)

Exclusion criteria

J4M-MC-PW01

• Prepubertal (Tanner stage 1)
• Have a self-reported, or by parent or legal guardian where applicable, decrease in body weight greater than 5 kilograms (kg) (11 pounds) within 90 days before screening

J4M-MC-PWMP

• Have undergone or plan to undergo weight reduction procedure during the study, such as, but not limited to:

• gastric bypass
• sleeve gastrectomy
• restrictive bariatric surgery, such as Lap-Band® gastric banding, or
• any other procedure intended to result in weight reduction.
• Have a diagnosis that is a secondary cause of obesity or have a history of abrupt onset of obesity suggesting a secondary cause, such as hypothalamic, monogenetic, syndromic, or endocrine causes.
• Have type 1 diabetes or history of ketoacidosis, or hyperosmolar state.
• Have HbA1c >9.0% (75 mmol/mol) as measured by central laboratory at screening.
• Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome Type 2.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 14 centers

• Carey Chronis MD Pediatric, Infant and Adolescent Medicine — Ventura
• Stamford Therapeutics Consortium — Stamford
• Children's Healthcare of Atlanta - Center for Advanced Pediatrics — Atlanta
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Velocity Clinical Research — Lafayette
• MedPharmics, LLC — Gulfport
• Sundance Clinical Research — St Louis
• Lucas Research, Inc. — Morehead City
• … and 6 more centers

Japan · 9 centers

• Saitama Medical University Hospital — Iruma-Gun
• Isesaki Municipal Hospital — Isesaki-shi
• University Hospital,Kyoto Prefectural University of Medicine — Kawaramachidori, Kamigyo-ku, Kyoto-city
• Tokyo Medical Center — Meguro-Ku
• Shiga General Hospital — Moriyama
• Nara Prefecture General Medical Center — Nara
• Osaka City General Hospital — Osaka
• Sagaekiminami Clinic — Saga
• … and 1 more center

United Kingdom · 5 centers

• Barnsley Hospital NHS Foundation Trust — Barnsley
• Addenbrookes Hospital — Cambridge
• Ninewells Hospital — Dundee
• Northwick Park Hospital — Harrow
• Hull Royal Infirmary — Hull

Poland · 4 centers

• Krakowskie Centrum Medyczne - FutureMeds — Krakow
• FutureMeds - Targowek — Warsaw
• Instytut Diabetologii - Warsaw — Warszewo
• FutureMeds sp. z o. o. — Wroclaw

Israel · 3 centers

• Shamir Medical Center — Beer Jacob
• Shaare Zedek Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan

Italy · 3 centers

• Azienda Ospedaliero Universitaria Meyer — Florence
• Azienda Ospedaliero Universitaria Maggiore della Carità — Novara
• Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento — Verona

Identifiers

NCT: NCT06672939 · 18868 · J4M-MC-PW01 · J4M-MC-PWMP Master Protocol · 2024-514081-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗