NCT06760546RecruitingPhase 3
A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity
Rhythm Pharmaceuticals, Inc.16 sites in 2 countries39 target enrollmentStarted: September 23, 2025Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Rhythm Pharmaceuticals, Inc.
- Enrollment
- 39
- Locations
- 16
- Primary Endpoint
- Mean % change in BMI
Study Overview
Brief Summary
This is a sub-study of Study RM-493-040 (NCT05774756).
The goal of this sub-study 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 congenital Hypothalamic Obesity (cHO). To determine how well setmelanotide works and how safe it is, patients with cHO will take a daily injection of either setmelanotide or placebo and complete trial assessments for up to 26 weeks on a therapeutic regimen.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 4 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Age 4 years and older
- •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
- •Agree to use a highly effective form of contraception throughout the study and for 90 days after the study
Exclusion Criteria
- •Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET)
- •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
- •Bariatric surgery or procedure within last 2 years
- •Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior
- •Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease
- •Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- •History or close family history of skin cancer or melanoma
- •Participation in any clinical trial with an investigational drug/device within 3 months prior to the first trial dose
- •Previously enrolled in a clinical trial involving setmelanotide or any previous exposure to setmelanotide
- •Inability to comply with once daily (QD) injection regimen
- •If female, pregnant and/or breastfeeding.
- •If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening
- •Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Setemelanotide
Experimental
Randomized 2:1 (Setmelanotide: Placebo)
Intervention: Setmelanotide (Drug)
Placebo
Placebo Comparator
Randomized 2:1 (Setmelanotide: Placebo)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Mean % change in BMI
Time Frame: From Baseline after 26 weeks on a therapeutic regimen
Secondary Outcomes
- 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 26 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 26 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 26 weeks on a therapeutic regimen)
- Mean change in Symptoms of Hyperphagia total score(From Baseline after 26 weeks on a therapeutic regimen)
- Proportion of patients with a ≥10% reduction in BMI(From Baseline after 26 weeks on a therapeutic regimen)
- Mean percent change in weight in patients ≥18 years(From Baseline after 26 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 26 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 26 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 26 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 26 weeks on a therapeutic regimen)
- 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 26 weeks on a therapeutic regimen)
Investigators
Study Sites (16)
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