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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06760546
- Acronym / sponsor ID
- RM-493-040-A
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Sep 2025 (actual)
- Primary completion
- 13 Mar 2027 (estimated)
- Study completion
- 13 Mar 2028 (estimated)
- First posted
- 7 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Setemelanotide | Experimental | Drug: SetmelanotideRandomized 2:1 (Setmelanotide: Placebo) |
| Placebo | Placebo comparator | Drug: PlaceboRandomized 2:1 (Setmelanotide: Placebo) |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SetmelanotideAlso: RM-493, ImcivreeSolution for daily subcutaneous injection | Drug | Setemelanotide |
| PlaceboPlacebo matched to setmelanotide for daily subcutaneous injection | Drug | Placebo |
Primary outcome
Mean % change in BMI
Time frame: From Baseline after 26 weeks on a therapeutic regimen
11 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)
Time frame: 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
Time frame: 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
Time frame: From Baseline after 26 weeks on a therapeutic regimen
Mean change in Symptoms of Hyperphagia total score
Time frame: From Baseline after 26 weeks on a therapeutic regimen
Proportion of patients with a ≥10% reduction in BMI
Time frame: From Baseline after 26 weeks on a therapeutic regimen
Mean percent change in weight in patients ≥18 years
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: From Baseline after 26 weeks on a therapeutic regimen
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- This is a sub-study of RM-493-040.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
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SEMAFORCRANIO : Multicenter, Double-blind, Parallel, Randomized Controlled Trial of the Efficacy of Semaglutide in Hypothalamic Obesity Secondary to Craniopharyngioma in Children Aged 12 to 17 Years
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Meeker, MD study chair
Rhythm Pharmaceuticals, Inc.
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rhythm Clinical Trials ((857) 264-4280, clinicaltrials@rhythmtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean % change in BMI (time frame: From Baseline after 26 weeks on a therapeutic regimen). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.