Setmelanotide for congenital hypothalamic obesity
A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity
This will test whether daily setmelanotide injections help reduce weight, curb hunger, and improve quality of life in people aged 4 and older with congenital hypothalamic obesity.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 39 (estimated) |
| Ages | 4 Years and up |
| Sex | All |
| Sponsor | Rhythm Pharmaceuticals, Inc. Industry-sponsored |
| Locations | 11 sites (Birmingham, Alabama and 10 other locations) |
| Trial ID | NCT06760546 on ClinicalTrials.gov |
What this trial studies
This Phase 3 sub-study enrolls people aged 4 years and older with congenital hypothalamic obesity secondary to conditions such as multiple pituitary hormone deficiency, septo-optic dysplasia, optic nerve hypoplasia, childhood-onset combined pituitary hormone deficiency, or pituitary stalk interruption syndrome. Participants will receive a daily injection of either setmelanotide or placebo and complete scheduled assessments for up to 26 weeks to measure weight change, hunger, and quality of life. Safety and tolerability will be monitored throughout the treatment period. The trial is run as a sub-study of a larger setmelanotide program and is conducted at three U.S. pediatric/adult endocrine centers.
Who should consider this trial
Good fit: Ideal candidates are people aged 4 years and older with congenital hypothalamic obesity related to MPHD, SOD, ONH, CPHD, or PSIS (with at least one pituitary deficiency) who meet the BMI criteria and agree to use effective contraception if applicable.
Not a fit: People with Prader-Willi syndrome or ROHHADNET, those who have lost more than 2% body weight in the past 3 months, or individuals whose obesity is not linked to hypothalamic/pituitary injury are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, setmelanotide could produce meaningful weight loss, reduce excessive hunger, and improve quality of life for people with congenital hypothalamic obesity.
How similar studies have performed: Setmelanotide has shown significant weight and hunger benefits in clinical trials and approvals for several rare genetic MC4R-pathway disorders, but its use for hypothalamic injury–related obesity is novel and less well established.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: 1. Diagnosis of multiple pituitary hormone deficiency (MPHD), or septo-optic dysplasia (SOD), or optic nerve hypoplasia (ONH), or Childhood-onset combined pituitary hormone deficiency (CPHD), or Pituitary Stalk Interruption Syndrome (PSIS) with at least one pituitary deficiency AND a body mass index (BMI) of ≥30 kg/m2 for patients ≥18 years of age, or BMI ≥95th percentile for age and sex for patients 4 to \<18 years 2. Age 4 years and older 3. Weight gain associated with the hypothalamic injury and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients 4 to \<18 years of age 4. Agree to use a highly effective form of contraception throughout the study and for 90 days after the study Key Exclusion Criteria: 1. Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET) 2. Weight loss \>2% in the previous 3 months for patients aged ≥18 years or \>2% reduction in BMI for patients aged 4 to \<18 years 3. Bariatric surgery or procedure within last 2 years 4. Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior 5. Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease 6. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) 7. History or close family history of skin cancer or melanoma 8. Participation in any clinical trial with an investigational drug/device within 3 months prior to the first trial dose 9. Previously enrolled in a clinical trial involving setmelanotide or any previous exposure to setmelanotide 10. Inability to comply with once daily (QD) injection regimen 11. If female, pregnant and/or breastfeeding. 12. If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening Other protocol defined Inclusion/Exclusion criteria may apply.
Where this trial is running
Birmingham, Alabama and 10 other locations
- University of Alabama — Birmingham, Alabama, United States (Recruiting)
- Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)
- Lurie Children's Hospital — Chicago, Illinois, United States (Recruiting)
- Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
- Children's Minnesota — Saint Paul, Minnesota, United States (Recruiting)
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
- Seattle Children's Research Institute — Seattle, Washington, United States (Recruiting)
- UCL Great Ormond Street Institute of Child Health — London, Greater London, United Kingdom (Recruiting)
- Birmingham Women and Children's Hospital NHS Trust — Birmingham, West Midlands, United Kingdom (Recruiting)
- Hull Royal Infirmary — Hull, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Rhythm Clinical Trials
- Email: clinicaltrials@rhythmtx.com
- Phone: (857) 264-4280
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.