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NCT Number: NCT06760546

A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)

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.

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Key information

Conditions

Hypothalamic Obesity Agenesis of Corpus Callosum Childhood-onset Combined Pituitary Hormone Deficiency Congenital Abnormalities Congenital Cranial Dysinnervation Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Disorders of Sex Development Endocrine System Diseases Eye Diseases Eye Diseases, Hereditary Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Gonadal Disorders Gonadal Dysgenesis Hypogonadism Male Urogenital Diseases Multiple Pituitary Hormone Deficiency Genetic Form Nervous System Diseases Nervous System Malformations Ocular Motility Disorders Oculomotor Nerve Diseases Optic Nerve Diseases Optic Nerve Hypoplasia Pituitary Stalk Interruption Syndrome Septo-Optic Dysplasia Sexual Infantilism Urogenital Abnormalities Urogenital Diseases

Age range

4 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

UCL Great Ormond Street Institute of Child Health, London, Greater London, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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

Key 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.

Treatment and study plan

Setmelanotide

Drug

Solution for daily subcutaneous injection

Other names: RM-493, Imcivree

Placebo

Drug

Placebo matched to setmelanotide for daily subcutaneous injection

Primary outcomes

  1. Mean % change in BMI

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

Secondary outcomes

  1. 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)

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  2. Mean change in the weekly average of the daily most hunger score in patients ≥12 years old

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  3. Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  4. Mean change in Symptoms of Hyperphagia total score

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  5. Proportion of patients with a ≥10% reduction in BMI

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  6. Mean percent change in weight in patients ≥18 years

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  7. Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2)

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  8. Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  9. Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years)

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  10. Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL)

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

  11. Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: From Baseline after 26 weeks on a therapeutic regimen

Study contacts

Contact information is provided by the study sponsor or research team.

Physician Inquiry Clinical Trials

CONTACT

[email protected]

(857) 264-4280

Rhythm Clinical Trials

CONTACT

[email protected]

(857) 264-4280

Sponsors and collaborators

Lead sponsor

Rhythm Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jan 7, 2025
Registry last updated
Feb 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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