A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Phase 3

Active, not recruiting

• Conditions: Hypothalamic Obesity
• Interventions: Drug: Placebo; Drug: Setmelanotide

• Registration Number: NCT05774756
• Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Brief Summary

The goal of this trial is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and older with acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for 52 weeks on a therapeutic regimen.

A separate sub-study in patients with congenital HO is detailed under NCT06760546.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-01
• Study First Submitted QC: 2023-03-16
• Study First Posted: 2023-03-20
• Study Start: 2023-04-26
• Primary Completion: 2025-03-18
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-02
• Study Completion: 2027-04-16

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Documented evidence of acquired hypothalamic obesity (HO)
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. Patients with obesity attributable to other genetic or syndromic conditions (eg, PPL [POMC, PCSK1, LEPR, collectively], BBS) prior to the hypothalamic injury.
13. If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomized 2:1 (Setmelanotide: Placebo)
Setemelanotide	Setmelanotide	Randomized 2:1 (Setmelanotide: Placebo)

Primary Outcome Measures

Name	Time	Method
Mean % change in BMI	From Baseline after 52 weeks on a therapeutic regimen

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Baseline after 52 weeks on a therapeutic regimen
Proportion of patients with ≥5% reduction in BMI in adult patients (≥18 years of age) or a BMI Z-score reduction of ≥0.2 points in pediatric patients (<18 years of age)	From Baseline after 52 weeks on a therapeutic regimen
Mean change in the weekly average of the daily most hunger score in patients ≥12 years old	From Baseline after 52 weeks on a therapeutic regimen
Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score	From Baseline after 52 weeks on a therapeutic regimen
Mean change in Symptoms of Hyperphagia total score	From Baseline after 52 weeks on a therapeutic regimen
Proportion of patients with a ≥10% reduction in BMI	From Baseline after 52 weeks on a therapeutic regimen
Mean percent change in weight in patients ≥18 years	From Baseline after 52 weeks on a therapeutic regimen
Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2)	From Baseline after 52 weeks on a therapeutic regimen
Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score	From Baseline after 52 weeks on a therapeutic regimen
Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years)	From Baseline after 52 weeks on a therapeutic regimen
Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL)	From Baseline after 52 weeks on a therapeutic regimen

Trial Locations

Locations (28)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Children's Minnesota; 🇺🇸 Saint Paul, Minnesota, United States

University Children's Hospital, Klinikum Oldenburg; 🇩🇪 Oldenburg, Germany

UAN Pediatric Endocrinology; 🇺🇸 Birmingham, Alabama, United States

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Ann and Robert H. Lurie Children's Hospital; 🇺🇸 Chicago, Illinois, United States

University of Iowa Stead Family Department of Pediatrics; 🇺🇸 Iowa City, Iowa, United States

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