Hypothalamic ObesityPhase 3NCT06760546
A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
A Phase 3 study testing Setmelanotide in people with Hypothalamic Obesity and Multiple Pituitary Hormone Deficiency Genetic Form, run by Rhythm Pharmaceuticals, Inc. at 11 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Hypothalamic Obesity, Multiple Pituitary Hormone Deficiency Genetic Form, Septo-Optic Dysplasia
- What is being tested?
- Setmelanotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 23 Sep 2025to 13 Mar 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
11 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 2 countries
United States8 sites, 8 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
- Recruiting
University of Alabama
Birmingham, Alabama, 35233
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
- Recruiting
Lurie Children's Hospital
Chicago, Illinois, 60611
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
- Recruiting
Children's Minnesota
Saint Paul, Minnesota, 55102
- Recruiting
Seattle Children's Research Institute
Seattle, Washington, 98105
United Kingdom3 sites, 3 recruiting
- Recruiting
Birmingham Women and Children's Hospital NHS Trust
Birmingham, West Midlands, B46NH
- Recruiting
Hull Royal Infirmary
Hull, HU32RW
- Recruiting
UCL Great Ormond Street Institute of Child Health
London, Greater London, WC1N 1EH
About this study
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
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.
- 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
- Being tested
- Setmelanotide, Placebo
- Keywords
- melancortin 4 receptor, MC4R
- Medical subject headings
- Sexual Infantilism, Septo-Optic Dysplasia, Optic Nerve Hypoplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Also called RM-493, Imcivree
Solution for daily subcutaneous injection
PlaceboDrug
Placebo matched to setmelanotide for daily subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Setemelanotide | Experimental | Randomized 2:1 (Setmelanotide: Placebo) Receives: Drug: Setmelanotide |
| Placebo | Placebo comparator | Randomized 2:1 (Setmelanotide: Placebo) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean % change in BMI
Measured: From Baseline after 26 weeks on a therapeutic regimen
Secondary outcomes (11)
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)
Measured: 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
Measured: 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
Measured: From Baseline after 26 weeks on a therapeutic regimen
Mean change in Symptoms of Hyperphagia total score
Measured: From Baseline after 26 weeks on a therapeutic regimen
Proportion of patients with a ≥10% reduction in BMI
Measured: From Baseline after 26 weeks on a therapeutic regimen
Mean percent change in weight in patients ≥18 years
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: From Baseline after 26 weeks on a therapeutic regimen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2025
- Study start23 Sep 2025
- Primary completion13 Mar 2027 (estimated)
- Study completion13 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypothalamic ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Meeker, MD, Study chair, Rhythm Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06760546
- Sponsor's protocol ID
- RM-493-040-A
- Status last verified
- Feb 2026
- First submitted
- 31 Dec 2024
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No