Hypothalamic ObesityPhase 3NCT05774756
A Trial of Setmelanotide in Acquired Hypothalamic Obesity
A Phase 3 study testing Setmelanotide in people with Hypothalamic Obesity, run by Rhythm Pharmaceuticals, Inc. at 28 sites in 6 countries.
Trial summary
The goal of this trial 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 acquired Hypothalamic Obesity (HO). Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Hypothalamic Obesity
- 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
- 143 participants
- Where
- 28 sitesin 6 countries
- Study dates
- 26 Apr 2023to 16 Apr 2027
- Phase
- Phase 3
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented evidence of acquired hypothalamic obesity (HO)
- 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 14Show 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
- Patients with obesity attributable to other genetic or syndromic conditions (eg, PPL [POMC, PCSK1, LEPR, collectively], BBS) prior to the hypothalamic injury.
- 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
28 sites in 6 countries.
28 sites in 6 countries
United States16 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
UAN Pediatric Endocrinology
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Ohio State Wexner Medical Center
Columbus, Ohio, 43203
University of Florida
Gainesville, Florida, 32610-0296
University of Iowa Stead Family Department of Pediatrics
Iowa City, Iowa, 52242
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Icahn School of Medicine at Mount Sinai
New York, New York, 100029
Columbia University Irving Medical Center
New York, New York, 10032
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73122
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Minnesota
Saint Paul, Minnesota, 55102
Rady Children's Hospital
San Diego, California, 92123
Seattle Children's Hospital, Research and Foundation - Center for Integrative Brain Research
Seattle, Washington, 98101
Germany4 sites
Universitaetsklinikum Hamburg-Eppendorf (UKE) - Ambulanzzentrum des UKE GmbH
Hamburg, 20246
Medicover Neuroendokrinologie
München, 81667
University Children's Hospital, Klinikum Oldenburg
Oldenburg, 26133
Universitaetsklinikum Ulm - Klinik fuer Kinder- und Jugendmedizin
Ulm, 89075
Japan3 sites
Nagano Children's Hospital
Azumino, Nagano, 399-8288
Toranomon Hospital
Minato, Tokyo, 105-8470
Nagoya City University Hospital
Nagoya, Aichi-ken, 467-8602
United Kingdom3 sites
Birmingham Women and Children's Hospital NHS Trust
Birmingham, B46NH
Hull University Teaching Hospital
Hull, HU32RW
UCL Great Ormond Street Institute of Child Health
London, WC1N 1EH
Netherlands1 site
Prinses Maxima Center for Pediatric Oncology
Utrecht, 3584CS
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
The goal of this trial 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 acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for 52 weeks on a therapeutic regimen.
A separate sub-study in patients with congenital HO is detailed under NCT06760546.
- Conditions
- Hypothalamic Obesity
- Being tested
- Setmelanotide, Placebo
- Keywords
- melancortin 4 receptor, MC4R
- 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
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.
Pivotal Cohort: Mean Percent Change From Baseline in Body Mass Index (BMI) After 52 Weeks on a Therapeutic Regimen
BMI was calculated as weight (kg)/height (m^2). Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Secondary outcomes (16)
Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI (≥18 Years of Age) or ≥0.2-point Reduction From Baseline in BMI Z-score (<18 Years of Age)
BMI was calculated as weight (kg)/height (m^2). BMI Z-Score calculated for participants <18 years old only is a measure of relative weight adjusted for child's age, sex and height at the time of data collection. The Z-Scores were calculated using the World Health Organization's WHO 2007 BMI SAS Macro Package. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. Results below represent the percentage of estimated participants with either ≥5% BMI reduction or ≥0.2 point reduction in BMI Z-score by age in each treatment arm as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI
BMI was calculated as weight (kg)/height (m^2). Results below represent the percentage of estimated participants with ≥5% BMI reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Change From Baseline in Weekly Average Daily Most Hunger Score in Participants ≥12 Years of Age
Change from baseline in hunger scores for participants ≥12 years of age with acquired hypothalamic obesity was evaluated. Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on an 11-point numeric rating scale. On Daily Hunger Questionnaire, each of the 2 items (average hunger and most hunger) was scored separately and averaged on weekly basis. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants (≥12 Years of Age) With a ≥2-point Reduction From Baseline in the Weekly Average Daily Most Hunger Score
Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on an 11-point numeric rating scale. On Daily Hunger Questionnaire, each of the 2 items (average hunger and most hunger) was scored separately and averaged on weekly basis. Results below represent the percentage of estimated participants ≥12 years of age with ≥2-point reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in the Weekly Average of the Symptoms of Hyperphagia Composite Score in Participants ≥12 Years of Age
Participants ≥12 years of age who were able to self-report were administered the Symptoms of Hyperphagia: Patient (Version 1.0). The questionnaire consisted of 4 items related to the frequency of a participant's hunger symptoms on a scale (Never, 1 or 2 times, 3 or more times) over the past 24 hours. The scores on this scale range from 0 to 2 with higher scores indicating more hyperphagia. Daily composite score was derived as the sum of daily answered questions divided by the number of answered questions per day. The weekly average of the daily composite scores equals to the sum of daily composite scores divided by the number of days with a composite score within the 7 identified days prior to the visit. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in BMI
BMI was calculated as weight (kg)/height (m^2). Results below represent the percentage of estimated participants with ≥10% BMI reduction in each treatment arm as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in Body Weight
Body weight was captured for analysis in kilograms. Results below represent the percentage of estimated participants with ≥10% reduction in body weight in each treatment arm as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Percent Change From Baseline in Body Weight in Participants ≥18 Years
Body weight was captured for analysis in kilograms. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in BMI Z-Score in Participants <18 Years of Age
BMI was calculated as weight (kg)/height (m^2). BMI Z-Score calculated for participants <18 years old only is a measure of relative weight adjusted for child's age, sex and height at the time of data collection. The Z-Scores were calculated using the World Health Organization's WHO 2007 BMI SAS Macro Package. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (> 0) indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Percent of BMI 95th Percentile in Participants <18 Years of Age
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. BMI percentile scores are measures of relative weight adjusted for child's age and gender. The percent of the BMI 95th percentile score expresses the participant's BMI as a percentage of the Centers for Disease Control (CDC) 95th percentile reference population. Baseline was defined as the most recent measurement prior to the first administration of study drug. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants <18 Years of Age With ≥0.2-Point Reduction From Baseline in BMI Z-Score
BMI was calculated as weight (kg)/height (m^2). BMI Z-Score calculated for participants <18 years old only is a measure of relative weight adjusted for child's age, sex and height at the time of data collection. The Z-Scores were calculated using the World Health Organization's WHO 2007 BMI SAS Macro Package. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease in BMI Z-score (< 0) indicates a reduction in BMI from Baseline whereas an increase in BMI-Z score (> 0) indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. Results below represent the percentage of estimated participants with ≥0.2 point reduction in BMI Z-score in each treatment arm and the difference between the treatment arms as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With BMI <30 kg/m^2 (Aged ≥18 Years) or <95th Percentile (Aged <18 Years) From Baseline
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. BMI Percentile scores are measures of relative weight adjusted for child's age and gender. The percent of the BMI 95th percentile score expresses the participant's BMI as a percentage of the CDC 95th percentile reference population. Baseline was defined as the most recent measurement prior to the first administration of study drug. Results below represent the percentage of estimated participants with either BMI <30 kg/m^2 (aged ≥18 years) or <95th percentile (aged <18 years) in each treatment arm and the difference between the treatment arms as calculated through the MIANALYZE SAS procedure.
Measured: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Physical Functioning Score and Total Score on the Impact of Weight on Quality of Life-Lite (IWQOL)
The IWQOL-Lite-Clinical Trials (administered to participants ≥18 years of age) is a validated 20-item self-report measure of obesity-specific quality of life questionnaire. It assessed 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items) and psychosocial (13 items). Each item was rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. It provided composite scores for each domain, as well as a total score, all ranging from 0 (worst) to 100 (best). Higher scores reflect better levels of functioning and quality of life. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Total Score on the Impact of Weight on Quality of Life-Kids (IWQOL-Kids)
The IWQOL-Kids (administered to participants between the ages of 11 and <18 years) is a validated 27-item self-report measure of weight-related quality of life for youth. It provided a total score inclusive of 4 domains: physical comfort, body esteem, social life, and family relations. Results below represent the total score, which is rated on a scale from 0 (worst) to 100 (best), with higher scores indicating better levels of functioning. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Waist Circumference
Waist circumference was captured for analysis in centimeters. LSM and SE were calculated using ANCOVA model.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Change From Baseline in Systolic and Diastolic Blood Pressure
Blood pressure was calculated in millimeters of mercury.
Measured: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start26 Apr 2023
- Primary completion18 Mar 2025
- Study completion16 Apr 2027 (estimated)
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 (3)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 143 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
- NCT05774756
- Sponsor's protocol ID
- RM-493-040
- Status last verified
- Jul 2026
- First submitted
- 1 Mar 2023
- Last updated
- 10 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Miller JL, van Santen HM, Phillips SA, Hamilton J, Aberle J, Sathyapalan T, Mohamed Z, McCormack SE, Shoemaker AH, Kelsey MM, Ghalib L, Stalla G, Thaker VV, Habiby R, Ode KL, Wabitsch M, Dattani M, Abuzzahab MJ, Abdullatif H, Morgan R, Stefater-Richards M, Aroda VR, Friedrich C, Han JC, Ono H, Nagasaki K, Tanaka T, Isojima T, Arima H, Scimia C, Yuan G, Muller HL, Roth CL; TRANSCEND Trial Group. Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med. 2026 Jul 9;395(2):138-150. doi: 10.1056/NEJMoa2512275.
PubMed 42418774Clement K, Roth CL, Kuhnen P, Haqq AM, Mallya UG, Ervin C, Norcross L, Bhargava S, Argente J, Miller JL. Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item. Adv Ther. 2026 Oct 1. doi: 10.1007/s12325-026-03741-x. Online ahead of print.
PubMed 42821228Roth CL, Phillips SA, McCormack SE, Ode KL, Kelsey MM, Liu J, Ervin C, Mallya UG, Norcross L, Miller JL. Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants. Front Behav Neurosci. 2026 Jul 15;20:1830070. doi: 10.3389/fnbeh.2026.1830070. eCollection 2026.
PubMed 42528856
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 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
- NCT05774756
- Acronym / sponsor ID
- RM-493-040
- Conditions
- Hypothalamic Obesity
- Keywords
- melancortin 4 receptor, MC4R
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Apr 2023 (actual)
- Primary completion
- 18 Mar 2025 (actual)
- Study completion
- 16 Apr 2027 (estimated)
- First posted
- 20 Mar 2023 (actual)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this trial 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 acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for 52 weeks on a therapeutic regimen.
A separate sub-study in patients with congenital HO is detailed under NCT06760546.
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)
- Documented evidence of acquired hypothalamic obesity (HO)
- 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 (14 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
Pivotal Cohort: Mean Percent Change From Baseline in Body Mass Index (BMI) After 52 Weeks on a Therapeutic Regimen
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
BMI was calculated as weight (kg)/height (m^2). Least square (LS) mean and standard error (SE) were calculated using analysis of covariance (ANCOVA) model.
16 secondary outcomes
Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI (≥18 Years of Age) or ≥0.2-point Reduction From Baseline in BMI Z-score (<18 Years of Age)
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With ≥5% Reduction From Baseline in BMI
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Change From Baseline in Weekly Average Daily Most Hunger Score in Participants ≥12 Years of Age
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants (≥12 Years of Age) With a ≥2-point Reduction From Baseline in the Weekly Average Daily Most Hunger Score
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in the Weekly Average of the Symptoms of Hyperphagia Composite Score in Participants ≥12 Years of Age
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in BMI
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With a ≥10% Reduction From Baseline in Body Weight
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Percent Change From Baseline in Body Weight in Participants ≥18 Years
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in BMI Z-Score in Participants <18 Years of Age
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Percent of BMI 95th Percentile in Participants <18 Years of Age
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants <18 Years of Age With ≥0.2-Point Reduction From Baseline in BMI Z-Score
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Percentage of Participants With BMI <30 kg/m^2 (Aged ≥18 Years) or <95th Percentile (Aged <18 Years) From Baseline
Time frame: After approximately 52 Weeks on a Therapeutic Regimen (baseline up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Physical Functioning Score and Total Score on the Impact of Weight on Quality of Life-Lite (IWQOL)
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Total Score on the Impact of Weight on Quality of Life-Kids (IWQOL-Kids)
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Mean Change From Baseline in Waist Circumference
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Pivotal Cohort: Change From Baseline in Systolic and Diastolic Blood Pressure
Time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 42418774Miller JL, van Santen HM, Phillips SA, Hamilton J, Aberle J, Sathyapalan T, Mohamed Z, McCormack SE, Shoemaker AH, Kelsey MM, Ghalib L, Stalla G, Thaker VV, Habiby R, Ode KL, Wabitsch M, Dattani M, Abuzzahab MJ, Abdullatif H, Morgan R, Stefater-Richards M, Aroda VR, Friedrich C, Han JC, Ono H, Nagasaki K, Tanaka T, Isojima T, Arima H, Scimia C, Yuan G, Muller HL, Roth CL; TRANSCEND Trial Group. Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med. 2026 Jul 9;395(2):138-150. doi: 10.1056/NEJMoa2512275.
- Derived from this study: PubMed 42821228Clement K, Roth CL, Kuhnen P, Haqq AM, Mallya UG, Ervin C, Norcross L, Bhargava S, Argente J, Miller JL. Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item. Adv Ther. 2026 Oct 1. doi: 10.1007/s12325-026-03741-x. Online ahead of print.
- Derived from this study: PubMed 42528856Roth CL, Phillips SA, McCormack SE, Ode KL, Kelsey MM, Liu J, Ervin C, Mallya UG, Norcross L, Miller JL. Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants. Front Behav Neurosci. 2026 Jul 15;20:1830070. doi: 10.3389/fnbeh.2026.1830070. eCollection 2026.
- Results from a qualitative follow-up interview study conducted among participants who completed NCT05774756; interviews were optional and not part of the registered clinical trial protocol.Link provided by the sponsor.
- 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.
28 sites in 6 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, run by Rhythm Pharmaceuticals, Inc. at 28 sites in 6 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 14 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: under way, not looking for participants, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Germany, Japan, United Kingdom, Canada and 1 more country. 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?
Yes. Results are posted in the registry (first posted 29 May 2026). 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?
Pivotal Cohort: Mean Percent Change From Baseline in Body Mass Index (BMI) After 52 Weeks on a Therapeutic Regimen (time frame: Baseline, after approximately 52 Weeks on a Therapeutic Regimen (up to approximately 60 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 NCT05774756, which also lists 3 linked publications.
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 10 Aug 2026.