Hypothalamic ObesityPhase 2NCT04725240
Open-Label Study of Setmelanotide in Hypothalamic Obesity
A Phase 2 study testing Setmelanotide in people with Hypothalamic Obesity, run by Rhythm Pharmaceuticals, Inc. at 5 sites in United States.
Trial summary
Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO). Read more about this study
- Who is it for?
- Ages 6 to 40 years
- Conditions the study is for
- Hypothalamic Obesity
- What is being tested?
- Setmelanotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesUnited States
- Study dates
- 7 Jun 2021to 28 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants must meet all of the following criteria to be eligible for study participation:
- Participant has documented evidence of HO, including:
- Recent evidence of hypothalamic injury on magnetic resonance imaging (MRI); AND
- Diagnosis of craniopharyngioma or other non-malignant brain tumor affecting the hypothalamic region; AND
- Has undergone surgery, or chemotherapy, or radiation ≥6 months and ≤15 years before Screening.
- Participant has either unilateral hypothalamic lesions or bilateral hypothalamic lesions, as assessed by MRI.
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- Obesity, documented by a body mass index (BMI) ≥35 kilograms/square meter (kg/m^2) for participants ≥18 years of age or BMI ≥95th percentile for age and gender for participants 6 to <18 years of age.
- Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.2 for participants <18 years of age or BMI >5% for participants >18 years of age) either during the first 6 months following surgery or within 1 year before surgery AND still present at Screening.
- More than 6 months after the end of post-tumor treatment, including chemotherapy, surgery, or radiation.
- Highly effective contraception throughout the study and for 90 days following the study.
- Ability to communicate well with the Investigator, understand and comply with the requirements of the study, and understand and sign the written informed consent, or, for participants aged <18 years, a parent/legal guardian that can sign.
- If receiving hormone replacement therapy, the dose of such therapy has remained stable for at least 2 months prior to Screening.
Who cannot join
- Participants meeting any of the following criteria are not eligible for study participation:
- Weight gain >5% in the previous 3 months.
- Weight loss ≥2% in the previous 3 months.
- Bariatric surgery or procedure within the last 6 months.
- Diagnosis of severe psychiatric disorders
- Glycated hemoglobin (HbA1c) >10.0% at Screening.
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- Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results.
- Glomerular filtration rate (GFR) <30mL/min/1.73m^2 during Screening.
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
- History or close family history (parents or siblings) of skin cancer or melanoma
- Participation in any clinical study with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first setmelanotide dose.
- Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
- Inability to comply with QD injection regimen.
- Pregnant and/or breastfeeding, or desiring to become pregnant during this trial.
- Cognitive impairment that, in the Investigator's opinion, precludes participation to the study and completions of study procedures or questionnaires.
- Participant is, in Investigator's opinion, otherwise not suitable to participate in the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Florida
Gainesville, Florida, 32610-0296
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Children's Minnesota
Saint Paul, Minnesota, 55102
Rady Children's Hospital
San Diego, California, 92123
Seattle Children's Research Institute
Seattle, Washington, 98101
About this study
Official title: A Phase 2, Open-Label 20-Week Study to Evaluate the Safety and Efficacy of Setmelanotide in Subjects With Hypothalamic Obesity
Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO).
- Conditions
- Hypothalamic Obesity
- Being tested
- Setmelanotide
- Medical subject headings
- Sexual Infantilism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Setmelanotide for SC injection
| Study group | Role | What they receive |
|---|---|---|
| Setmelanotide | Experimental | Participants received setmelanotide once daily (QD) via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and dose escalated up to a maximum dose of 3.0 milligrams (mg) QD. Receives: Drug: Setmelanotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline to 16 weeks
Secondary outcomes (9)
Composite Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score or Participants Aged ≥18 Years With 5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
For participants aged ≥6 to <18 years, a participant's BMI Z-score was considered for the analysis; for participants ≥18 years, a participant's body weight (kg) was considered for the analysis. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline to Week 16
Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score From Baseline After 16 Weeks of Setmelanotide Treatment
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline to 16 weeks
Percentage of Participants Aged ≥18 Years With ≥5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline to Week 16
Change From Baseline in Waist Circumference in Participants Aged ≥18 Years After 16 Weeks of Setmelanotide Treatment
Waist circumference was measured after participants had fasted for at least 8 hours and at approximately the same time at each visit. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 16
Change From Baseline in Daily Hunger Questionnaire Score in Participants Aged <12 Years After 16 Weeks of Setmelanotide Treatment
Daily Hunger Questionnaire for participants <12 years of age: Three aspects of hunger (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) were assessed daily using a pictorial (smiley face) version of the Likert rating scale with scores from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible. Responses were recorded in the electronic diary. Each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged to calculate a total score ranging from 0 (not hungry at all) to 4 (hungriest possible) with higher score indicating more hunger. Baseline daily hunger score was calculated as the average of 7 days prior to Baseline visit.
Measured: Baseline, Week 16
Change From Baseline in Daily Hunger Questionnaire Scores in Participants Aged ≥12 Years After 16 Weeks of Setmelanotide Treatment
Daily Hunger Questionnaire for participants ≥12 years of age: Three aspects of hunger (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) were assessed daily using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible. The responses to the Daily Hunger Questionnaire were recorded in the electronic diary. Baseline daily hunger score was calculated as the average of 7 days prior to Baseline visit.
Measured: Baseline, Week 16
Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged < 12 Years
Parents or caregivers of participants <12 years old answered the Caregiver Reported Global Hunger Question for participants who were <12 years old. The following question was asked: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; and Extremely hungry. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 16
Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged ≥12 Years
Global Hunger Questionnaire for participants ≥12 years of age. The following question was asked: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; and Severe hunger. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 16
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence or clinically significant worsening of an existing condition associated with the use of a drug in humans, whether or not considered drug related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Measured: From first dose of study drug up to Day 141
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2021
- Study start7 Jun 2021
- Primary completion28 Jun 2022
- Study completion28 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
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
- NCT04725240
- Sponsor's protocol ID
- RM-493-030
- Other IDs
- 2022-004107-32
- Status last verified
- Jan 2025
- First submitted
- 6 Jan 2021
- Last updated
- 7 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. doi: 10.1016/S2213-8587(24)00087-1. Epub 2024 Apr 30.
PubMed 38697184
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label 20-Week Study to Evaluate the Safety and Efficacy of Setmelanotide in Subjects With Hypothalamic Obesity
- ClinicalTrials.gov ID
- NCT04725240
- Acronym / sponsor ID
- RM-493-030
- Conditions
- Hypothalamic Obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Jun 2021 (actual)
- Primary completion
- 28 Jun 2022 (actual)
- Study completion
- 28 Jun 2022 (actual)
- First posted
- 26 Jan 2021 (actual)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Setmelanotide | Experimental | Drug: SetmelanotideParticipants received setmelanotide once daily (QD) via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and dose escalated up to a maximum dose of 3.0 milligrams (mg) QD. |
Who may qualify
- Ages
- 6 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Participants must meet all of the following criteria to be eligible for study participation:
- Participant has documented evidence of HO, including:
- Participant has either unilateral hypothalamic lesions or bilateral hypothalamic lesions, as assessed by MRI.
- Obesity, documented by a body mass index (BMI) ≥35 kilograms/square meter (kg/m^2) for participants ≥18 years of age or BMI ≥95th percentile for age and gender for participants 6 to <18 years of age.
- Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.2 for participants <18 years of age or BMI >5% for participants >18 years of age) either during the first 6 months following surgery or within 1 year before surgery AND still present at Screening.
Key exclusion criteria (16 listed)
- Participants meeting any of the following criteria are not eligible for study participation:
- Weight gain >5% in the previous 3 months.
- Weight loss ≥2% in the previous 3 months.
- Bariatric surgery or procedure within the last 6 months.
- Diagnosis of severe psychiatric disorders
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 |
|---|---|---|
| SetmelanotideSetmelanotide for SC injection | Drug | Setmelanotide |
Primary outcome
Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline to 16 weeks
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.
9 secondary outcomes
Composite Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score or Participants Aged ≥18 Years With 5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline to Week 16
Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score From Baseline After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline to 16 weeks
Percentage of Participants Aged ≥18 Years With ≥5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline to Week 16
Change From Baseline in Waist Circumference in Participants Aged ≥18 Years After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline, Week 16
Change From Baseline in Daily Hunger Questionnaire Score in Participants Aged <12 Years After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline, Week 16
Change From Baseline in Daily Hunger Questionnaire Scores in Participants Aged ≥12 Years After 16 Weeks of Setmelanotide Treatment
Time frame: Baseline, Week 16
Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged < 12 Years
Time frame: Baseline, Week 16
Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged ≥12 Years
Time frame: Baseline, Week 16
Number of Participants With Adverse Events (AEs)
Time frame: From first dose of study drug up to Day 141
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 38697184Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. doi: 10.1016/S2213-8587(24)00087-1. Epub 2024 Apr 30.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
David Meeker, MD study chair
Rhythm Pharmaceuticals, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Setmelanotide in people with Hypothalamic Obesity, run by Rhythm Pharmaceuticals, Inc. at 5 sites in United States.
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 12 inclusion and 16 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: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment (time frame: Baseline to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04725240, which also lists 1 linked publication.
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 7 Feb 2025.