Clinical trial NCT06760546: A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
Official title: A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hypothalamic Obesity
Multiple Pituitary Hormone Deficiency Genetic Form
Septo-Optic Dysplasia
Optic Nerve Hypoplasia
Childhood-onset Combined Pituitary Hormone Deficiency
Pituitary Stalk Interruption Syndrome
Keywords: melancortin 4 receptor, MC4R
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-07
Enrollment: 39
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Mean % change in BMI
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
Secondary outcomes:
measure: 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)
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Mean change in the weekly average of the daily most hunger score in patients ≥12 years old
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Mean change in Symptoms of Hyperphagia total score
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Proportion of patients with a ≥10% reduction in BMI
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Mean percent change in weight in patients ≥18 years
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2)
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years)
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL)
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
measure: Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline after 26 weeks on a therapeutic regimen
Other outcomes:
Locations:
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References: