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Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03013543
Recruitment Status : Active, not recruiting
First Posted : January 6, 2017
Last Update Posted : July 16, 2021
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.

Brief Summary:
The purpose of the study is to determine the effect of setmelanotide (RM-493) on weight, hunger assessments and other factors in patients with rare genetic disorders of obesity.

Condition or disease Intervention/treatment Phase
Pro-opiomelanocortin (POMC) Deficiency Obesity (Heterozygous or Epigenetic) Leptin Receptor Deficiency Obesity Smith-Magenis Syndrome Obesity Due to Melanocortin 4 Receptor Deficiency (Disorder) Drug: Setmelanotide Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
Actual Study Start Date : January 2017
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Setmelanotide
Setmelanotide subcutaneous injection once daily
Drug: Setmelanotide
RM-493 once daily subcutaneous injection
Other Name: RM-493

Primary Outcome Measures :
  1. Effect of Setmelanotide on Body Weight Reduction [ Time Frame: 1 year ]
    The proportion of patients in each subgroup of RGDO who achieve at least 5% body weight reduction from baseline, at ~3 months treatment with setmelanotide.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with the following genotypes and/or clinical assessment:

    1. POMC/PCSK1/LEPR heterozygous - not currently enrolling new patients
    2. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
    3. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity - not currently enrolling new patients
    4. Smith-Magenis Syndrome (SMS)
    5. SH2B1 deficiency obesity - not currently enrolling new patients
    6. Chromosomal rearrangement of the 16p11.2 locus causing obesity - not currently enrolling new patients
    7. CPE compound heterozygous or homozygous deficiency obesity
    8. Leptin deficiency obesity with loss of response to metreleptin
    9. SRC1 deficiency obesity - not currently enrolling new patients
    10. MC4R deficiency obesity - not currently enrolling new patients

    Note: The specific genotype for all patients must be reviewed by the Sponsor prior to study enrollment to confirm that the patient meets Inclusion Criterion #1. In addition, enrollment of patients in some subgroups may be prioritized by the Sponsor in order to ensure enrollment of patients with (1) well described, loss-of-function genetic mutations, (2) a variety of genetic variants, or (3) genetic variants likely to respond to setmelanotide.

  2. Age 6 years and above.
  3. Obese, defined as Body Mass Index (BMI) ≥ 30 kg/m2 for patients ≥16 years of age or BMI≥ 95th percentile for age and gender for patients 6 up to 16 years of age.
  4. Study participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study, and is able to understand and sign the written informed consent/assent.
  5. Female participants of child-bearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening Follicle-Stimulating Hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study.
  6. Male participants with female partners of childbearing potential must agree to a doublebarrier method if they become sexually active during the study. Male patients must not donate sperm during and for 90 days following their participation in the study.

Exclusion Criteria:

  1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in > 2% weight loss.
  2. 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). Note:Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as (1) is it not being prescribed for the treatment of obesity, (2) the dose has been stable for at least three months prior to enrollment, (3) the patient has not experienced weight loss during the previous three months, AND (4) the patient intends to keep the dose stable throughout the course of the study.
  3. Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. Specifically, patients may be considered if surgery was not successful, or resulted in <10% weight loss compared to pre-operative baseline weight or clear evidence of weight regain after an initial response to bariatric surgery. All patients with a history of bariatric surgery must be discussed with and receive approval from the Sponsor prior to enrollment.
  4. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance.

    Neurocognitive disorders affecting ability to consent will not be disqualifying as long as an appropriate guardian able to give consent has been appointed.

  5. A PHQ-9 score of ≥ 15 or any suicidal ideation of type 4 or 5 on the C-SSRS during Screening, any lifetime history of a suicide attempt, or any suicidal behavior in the last month. Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be allowed to enroll in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
  6. Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.
  7. HbA1c >9.0% at Screening
  8. History of significant liver disease or abnormal liver tests on Screening (i.e. > 1.5 x upper limit of normal [ULN] for alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin). Note: Patients entering the study with SRC1 haploinsufficiency obesity must be evaluated during the Screening Period for hepatic fibrosis by appropriate imaging techniques (e.g., transient elastography or magnetic resonance elastography). Any patient with moderate or greater fibrosis (e.g., the equivalent of a METAVIR score ≥ 2) will be excluded from the study. Note: A patient with a diagnosis of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) may be allowed to enroll in the study, after consultation with the Sponsor. Other significant liver disease, such as cirrhosis, are exclusionary.
  9. Glomerular filtration rate (GFR) <30 mL/min at Screening.
  10. History or close family history (parents or siblings) of skin cancer or melanoma (not including non-invasive/infiltrative basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.
  11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by a qualified dermatologist during Screening.

    Any concerning lesions identified during the Screening Period will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study.

  12. Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
  13. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  14. Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
  15. Significant hypersensitivity to any excipient in the study drug.
  16. Inability to comply with QD injection regimen.
  17. Females who are breastfeeding or nursing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03013543

Hide Hide 57 study locations
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United States, Alabama
Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC
Birmingham, Alabama, United States, 35211
United States, Arizona
Synexus Clinical Research US, Inc. - Phoenix Southeast
Chandler, Arizona, United States, 85224
Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
Mesa, Arizona, United States, 85206
Honor Health Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
Axis Clinical Trials-Downtown
Los Angeles, California, United States, 90017
Axis Clinical Trials Headquarters
Los Angeles, California, United States, 90036
San Diego Wake Research
San Diego, California, United States, 92108
United States, Colorado
Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States, 80045
United States, District of Columbia
Division of Endocrinology and Diabetes Children's National Hospital
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610
AXIS South Florida Clinical Trials
Hialeah, Florida, United States, 33016
Florida Hospital
Orlando, Florida, United States, 32804
Synexus Clinical Research US, Inc. - St. Petersburg
Pinellas Park, Florida, United States, 33781
United States, Illinois
Synexus Clinical Research US, Inc. - Chicago
Chicago, Illinois, United States, 60602
United States, Maine
Maine Medical Partners
Portland, Maine, United States, 04102
United States, Maryland
NIH Hatfield Clinical Research Center
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Baystate Medical Center
Springfield, Massachusetts, United States, 01107
United States, Michigan
University of Michigan Medicine
Ann Arbor, Michigan, United States, 48105
United States, Minnesota
Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University St. Louis
Saint Louis, Missouri, United States, 63110
United States, Nevada
Impact Clinical Trials
Las Vegas, Nevada, United States, 89106
United States, New York
AXIS New York Clinical Trials
Brooklyn, New York, United States, 11201
University at Buffalo
Buffalo, New York, United States, 14203
AXIS Clinical Trials
New York, New York, United States, 10022
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10025
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Wake Research Inc.
Raleigh, North Carolina, United States, 27612
United States, Ohio
Synexus Clinical Research US, Inc. - Akron
Akron, Ohio, United States, 44311
Synexus Clinical Research US, Inc. - Cincinnati
Cincinnati, Ohio, United States, 45236
Synexus Clinical Research US, Inc. - Columbus
Columbus, Ohio, United States, 43016
United States, Pennsylvania
Obesity Institute, Geisinger Clinic
Danville, Pennsylvania, United States, 17822
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Synexus Clinical Research US, Inc. - Primary Care Associates, PC
Anderson, South Carolina, United States, 29621
United States, Tennessee
Wake Research TN
Chattanooga, Tennessee, United States, 37421
Le Bonheur Children's Hospital
Memphis, Tennessee, United States, 38103
Vanderbilt University School of Medicine
Nashville, Tennessee, United States, 37212-3157
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Synexus Clinical Research US, Inc. - Plano
Plano, Texas, United States, 75093
Synexus Clinical Research US, Inc. - San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Children's Research Institute
Seattle, Washington, United States, 98101
United States, Wisconsin
Marshfield Clinic Research Institute
Marshfield, Wisconsin, United States, 54449
University of Alberta
Edmonton, Canada, T6G 2E1
Hopital Trousseau - Nutrition et Gastroentérologie
Paris, France, 75012
Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon
Saint-Denis, France, 97405
Charité Berlin
Berlin, Germany, 13354
University of Leipzig
Leipzig, Germany, 04103
University of Ulm
Ulm, Germany, 89075
University General Hospital of Patras
Río, Patras, Greece, 26504
Edmond and Lily Safra Children's Hospital
Ramat Gan, Israel, 52621
Erasmus MC
Rotterdam, Netherlands, 3015 CE
Hospital Infantil Universitario Niño Jesús
Madrid, Spain, 65 28009
United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom, B15 2TH
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Hammersmith Hospital
London, United Kingdom, W12 0NN
Hammersmith Hospital
London, United Kingdom
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
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Study Chair: Murray Stewart, BM/DM Rhythm Pharmaceuticals, Inc.
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Responsible Party: Rhythm Pharmaceuticals, Inc. Identifier: NCT03013543    
Other Study ID Numbers: RM-493-014
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: July 16, 2021
Last Verified: July 2021
Keywords provided by Rhythm Pharmaceuticals, Inc.:
POMC deficiency obesity
LepR deficiency obesity
Smith-Magenis Syndrome
MC4R deficiency obesity
SRC1 deficiency obesity
SH2B1 deficiency obesity
Additional relevant MeSH terms:
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Smith-Magenis Syndrome
Genetic Diseases, Inborn
Obesity, Morbid
Nutrition Disorders
Body Weight
Chronobiology Disorders
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders