Childhood-onset Combined Pituitary Hormone Deficiency, Hypothalamic Obesity, Multiple Pituitary Hormone Deficiency Genetic Form, Optic Nerve Hypoplasia, Pituitary Stalk Interruption Syndrome, Septo-Optic Dysplasia
Conditions
Keywords
melancortin 4 receptor, MC4R
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.
Interventions
DRUGSetmelanotide
Solution for daily subcutaneous injection
DRUGPlacebo
Placebo matched to setmelanotide for daily subcutaneous injection
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean % change in BMI | From Baseline after 26 weeks on a therapeutic regimen |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United Kingdom, United States
Contacts
CONTACTRhythm Clinical Trials
CONTACTPhysician Inquiry Clinical Trials
STUDY_CHAIRDavid Meeker, MD
Rhythm Pharmaceuticals, Inc.
Outcome results
None listed