Genetic ObesityPhase 2NCT03013543
Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
A Phase 2 study testing Setmelanotide in people with Genetic Obesity and Obesity, run by Rhythm Pharmaceuticals, Inc. at 58 sites in 9 countries.
Trial summary
The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Genetic Obesity, Obesity, Obesity Due to Melanocortin 4 Receptor Deficiency
- 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
- 213 participants
- Where
- 58 sitesin 9 countries
- Study dates
- 10 Feb 2017to 1 Mar 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants with the following genotypes and/or clinical assessment:
- POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants
- POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
- POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity
- SMS
- SH2B1 deficiency obesity
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- Chromosomal rearrangement of the 16p11.2 locus causing obesity
- Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity
- Leptin deficiency obesity with loss of response to metreleptin
- SRC1 deficiency obesity
- MC4R deficiency obesity
- Age 6 years and above
- Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age.
- Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
- Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
- Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study.
Who cannot join
- Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in > 2% weight loss.
- Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).
- Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
- Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
- Clinically significant pulmonary, cardiac, or oncologic disease
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- hemoglobin A1c (HbA1c) > 9.0% at Screening
- History of significant liver disease
- Glomerular filtration rate (GFR) < 30 milliliter/minute (mL/min) at Screening.
- History or close family history of melanoma or participant history of oculocutaneous albinism
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
- Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
- Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
- Inability to comply with QD injection regimen.
- Females who are breastfeeding or nursing.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
58 sites in 9 countries.
58 sites in 9 countries
United States43 sites
Synexus Clinical Research US, Inc. - Akron
Akron, Ohio, 44311
Synexus Clinical Research US, Inc. - Primary Care Associates, PC
Anderson, South Carolina, 29621
University of Michigan Medicine
Ann Arbor, Michigan, 48105
Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
NIH Hatfield Clinical Research Center
Bethesda, Maryland, 20892
Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC
Birmingham, Alabama, 35211
AXIS New York Clinical Trials
Brooklyn, New York, 11201
University at Buffalo
Buffalo, New York, 14203
Synexus Clinical Research US, Inc. - Phoenix Southeast
Chandler, Arizona, 85224
Wake Research TN
Chattanooga, Tennessee, 37421
Synexus Clinical Research US, Inc. - Chicago
Chicago, Illinois, 60602
Synexus Clinical Research US, Inc. - Cincinnati
Cincinnati, Ohio, 45236
Synexus Clinical Research US, Inc. - Columbus
Columbus, Ohio, 43016
Obesity Institute, Geisinger Clinic
Danville, Pennsylvania, 17822
Duke University Medical Center
Durham, North Carolina, 27705
University of Florida College of Medicine
Gainesville, Florida, 32610
AXIS South Florida Clinical Trials
Hialeah, Florida, 33016
Baylor College of Medicine
Houston, Texas, 77030
Impact Clinical Trials
Las Vegas, Nevada, 89106
Axis Clinical Trials-Downtown
Los Angeles, California, 90017
Axis Clinical Trials Headquarters
Los Angeles, California, 90036
Marshfield Clinic Research Institute
Marshfield, Wisconsin, 54449
Le Bonheur Children's Hospital
Memphis, Tennessee, 38103
Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
Mesa, Arizona, 85206
Vanderbilt University School of Medicine
Nashville, Tennessee, 37212-3157
AXIS Clinical Trials
New York, New York, 10022
Icahn School of Medicine at Mount Sinai
New York, New York, 10025
Columbia University
New York, New York, 10032
Florida Hospital
Orlando, Florida, 32804
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Synexus Clinical Research US, Inc. - St. Petersburg
Pinellas Park, Florida, 33781
Synexus Clinical Research US, Inc. - Plano
Plano, Texas, 75093
Maine Medical Partners
Portland, Maine, 04102
Wake Research Inc.
Raleigh, North Carolina, 27612
Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84132
Synexus Clinical Research US, Inc. - San Antonio
San Antonio, Texas, 78229
San Diego Wake Research
San Diego, California, 92108
Honor Health Research Institute
Scottsdale, Arizona, 85258
Seattle Children's Research Institute
Seattle, Washington, 98101
Baystate Medical Center
Springfield, Massachusetts, 01107
Washington University St. Louis
St Louis, Missouri, 63110
Division of Endocrinology and Diabetes Children's National Hospital
Washington D.C., District of Columbia, 20010
United Kingdom4 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH
Addenbrooke's Hospital
Cambridge, CB2 0QQ
Hammersmith Hospital
London, W12 0NN
Hammersmith Hospital
London
France3 sites
Hopital Trousseau - Nutrition et Gastroentérologie
Paris, 75012
Hopital de la Pitié-Salpêtrière
Paris, 75013
Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon
Saint-Denis, 97405
Germany3 sites
Charité Berlin
Berlin, 13354
University of Leipzig
Leipzig, 04103
University of Ulm
Ulm, 89075
About this study
Official title: Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.
- Being tested
- Setmelanotide
- Keywords
- Pro-opiomelanocortin (POMC) deficiency obesity, LepR deficiency obesity, Smith-Magenis Syndrome, MC4R deficiency obesity, SRC1 deficiency obesity, SH2B1 deficiency obesity
- Medical subject headings
- Obesity, Smith-Magenis Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Also called RM-493
RM-493 QD SC injection
| Study group | Role | What they receive |
|---|---|---|
| 16p11.2 Cohort | Experimental | Participants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| AS Cohort | Experimental | Participants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| BBS Cohort | Experimental | Participants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| MC4R Cohort | Experimental | Participants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| POMC/PCSK1/LEPR Heterozygous Cohort | Experimental | Participants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| POMC/PCSK1/LEPR Composite Heterozygous Cohort | Experimental | Participants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| POMC/PCSK1/LEPR Compound Heterozygous Cohort | Experimental | Participants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| SH2B1 Cohort | Experimental | Participants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| SMS Cohort | Experimental | Participants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
| SRC1 Cohort | Experimental | Participants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. Receives: Drug: Setmelanotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
Measured: Baseline to Month 3
Secondary outcomes (8)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence 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. TEAEs were defined as AEs reported after dosing on Day 1.
Measured: From first dose up to Month 16
Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Measured: Baseline, Month 3
Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Measured: Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
The mean change in daily hunger questionnaire scores for participants ≥ 12 years of age with obesity in treatment with setmelanotide was evaluated. On the Daily Hunger Questionnaire, each of the 3 items (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) was assessed daily and scored separately using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible.
Measured: Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
The mean change in daily hunger questionnaire scores for participants < 12 years of age with obesity in treatment with setmelanotide was evaluated. Hunger was assessed daily using a Daily Hunger Questionnaire with a pictorial (smiley face) version of the Likert rating scale with scores ranged from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible.
Measured: Baseline, Month 3
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
For participants ≥ 12 years of age, the following question was asked using the Global Hunger Questionnaire: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; Severe hunger; and Not answered.
Measured: Baseline, Month 3
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
For participants < 12 years of age, the following question was asked to parents or caregivers of participants using the Global Hunger Questionnaire: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; Extremely hungry; and Not answered.
Measured: Baseline, Month 3
Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment
Waist circumference (cm) was measured according to the National Heart, Lung, and Blood Institute (NHLBI) criteria. All measurements were single measures. Waist circumference was measured when participants were in fasting condition and at approximately the same time at each visit.
Measured: Baseline, Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2017 (estimated)
- Study start10 Feb 2017
- Primary completion1 Mar 2022
- Study completion1 Mar 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 (2)Papers the sponsor has linked to this study.
- Other trials for Genetic 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 213 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
- NCT03013543
- Sponsor's protocol ID
- RM-493-014
- Other IDs
- 2017-000387-14, 2017
- Status last verified
- Jul 2023
- First submitted
- 3 Jan 2017
- Last updated
- 18 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ervin C, Norcross L, Mallya UG, Fehnel S, Mittleman RS, Webster M, Haqq AM, Haws RM. Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome. Adv Ther. 2023 May;40(5):2394-2411. doi: 10.1007/s12325-023-02443-y. Epub 2023 Mar 24.
PubMed 36961653Meyer JR, Krentz AD, Berg RL, Richardson JG, Pomeroy J, Hebbring SJ, Haws RM. Kidney failure in Bardet-Biedl syndrome. Clin Genet. 2022 Apr;101(4):429-441. doi: 10.1111/cge.14119.
PubMed 35112343
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
- ClinicalTrials.gov ID
- NCT03013543
- Acronym / sponsor ID
- RM-493-014
- Keywords
- Pro-opiomelanocortin (POMC) deficiency obesity, LepR deficiency obesity, Smith-Magenis Syndrome, MC4R deficiency obesity, SRC1 deficiency obesity, SH2B1 deficiency obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Feb 2017 (actual)
- Primary completion
- 1 Mar 2022 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 6 Jan 2017 (estimated)
- Results
- Posted 18 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| 16p11.2 Cohort | Experimental | Drug: SetmelanotideParticipants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| AS Cohort | Experimental | Drug: SetmelanotideParticipants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| BBS Cohort | Experimental | Drug: SetmelanotideParticipants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| MC4R Cohort | Experimental | Drug: SetmelanotideParticipants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| POMC/PCSK1/LEPR Heterozygous Cohort | Experimental | Drug: SetmelanotideParticipants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| POMC/PCSK1/LEPR Composite Heterozygous Cohort | Experimental | Drug: SetmelanotideParticipants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| POMC/PCSK1/LEPR Compound Heterozygous Cohort | Experimental | Drug: SetmelanotideParticipants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| SH2B1 Cohort | Experimental | Drug: SetmelanotideParticipants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| SMS Cohort | Experimental | Drug: SetmelanotideParticipants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
| SRC1 Cohort | Experimental | Drug: SetmelanotideParticipants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Participants with the following genotypes and/or clinical assessment:
- Age 6 years and above
- Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age.
- Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
- Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
Key exclusion criteria (16 listed)
- Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in > 2% weight loss.
- Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).
- Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
- Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
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-493RM-493 QD SC injection | Drug | 16p11.2 Cohort, AS Cohort, BBS Cohort, MC4R Cohort, POMC/PCSK1/LEPR Composite Heterozygous Cohort, POMC/PCSK1/LEPR Compound Heterozygous Cohort, POMC/PCSK1/LEPR Heterozygous Cohort, SH2B1 Cohort, SMS Cohort, SRC1 Cohort |
Primary outcome
Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
Time frame: Baseline to Month 3
8 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose up to Month 16
Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Time frame: Baseline, Month 3
Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Time frame: Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
Time frame: Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
Time frame: Baseline, Month 3
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
Time frame: Baseline, Month 3
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
Time frame: Baseline, Month 3
Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment
Time frame: Baseline, Month 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36961653Ervin C, Norcross L, Mallya UG, Fehnel S, Mittleman RS, Webster M, Haqq AM, Haws RM. Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome. Adv Ther. 2023 May;40(5):2394-2411. doi: 10.1007/s12325-023-02443-y. Epub 2023 Mar 24.
- Derived from this study: PubMed 35112343Meyer JR, Krentz AD, Berg RL, Richardson JG, Pomeroy J, Hebbring SJ, Haws RM. Kidney failure in Bardet-Biedl syndrome. Clin Genet. 2022 Apr;101(4):429-441. doi: 10.1111/cge.14119.
- 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.
58 sites in 9 countries: 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 Genetic Obesity and Obesity, run by Rhythm Pharmaceuticals, Inc. at 58 sites in 9 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 16 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 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 58 sites in United States, United Kingdom, France, Germany, Canada and 4 more countries. 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 18 Aug 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?
Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment (time frame: Baseline to Month 3). 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 NCT03013543, which also lists 2 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 18 Aug 2023; AzTrials last refreshed its copy on 7 Nov 2026.