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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03013543
Recruitment Status : Recruiting
First Posted : January 6, 2017
Last Update Posted : December 6, 2018
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, including POMC deficiency, LepR deficiency, Bardet-Biedl syndrome and Alström syndrome.

Condition or disease Intervention/treatment Phase
Pro-opiomelanocortin (POMC) Deficiency Obesity (Heterozygous or Epigenetic) Leptin Receptor Deficiency Obesity Bardet-Biedl Syndrome Alstrom Syndrome Smith-Magenis Syndrome Drug: Setmelanotide Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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 : May 2021
Estimated Study Completion Date : August 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 on weight loss [ Time Frame: 1 year ]
    Measurement of the effect of RM-493 on weight loss.

Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 1 year ]
    Assessment of Adverse Events related to treatment

  2. Effect on Body Fat Mass [ Time Frame: 1 year ]
    Assessment of body composition as measured by bioelectrical impedance (BIA) or Dual-energy x-ray absorptiometry (DXA).

  3. Effect on Hunger [ Time Frame: 1 year ]
    Assessment of hunger using a Hunger Questionnaire.

  4. Effects on insulin sensitivity [ Time Frame: 1 year ]
    Ratios and HOMA-IR assessments of oral glucose tolerance test (OGTT) and immune-reactive insulin (IRI) levels.

  5. Effect on Waist Circumference [ Time Frame: 1 year ]
    Assessment of waist circumference.

  6. Reversal of weight during the off treatment withdrawal phase [ Time Frame: 2 to 4 weeks ]
    Assessment of weight regain during the withdrawal phase

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Rare genetic disease patients genetically confirmed diagnoses (may be confirmed by test at Screening) of:

    1. Homozygous or compound heterozygous (different gene mutation on both alleles) LEPR mutations
    2. Heterozygous POMC mutations
    3. POMC hypermethylation (epigenetic) variants (>51.92 % POMC methylation intensity at the specific analyzed POMC region)
    4. Bardet-Biedl Syndrome (BBS)
    5. Alström Syndrome
    6. LEPR Heterozygous Deficiency Obesity
    7. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC, PCSK1, or LEPR genes, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype.
    8. Smith-Magenis Syndrome (SMS)
  2. Age 12 years and above.
  3. If adult age ≥18 years, obesity with body mass index (BMI) ≥ 30 kg/m2; if age 12 and above, obesity with weight > 97th percentile for age and sex on growth chart assessment.
  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 be 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 FSH level in the post-menopausal lab range), or delayed pubertal development 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 double barrier 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. Patients may be reconsidered approximately 1 month after cessation of such intensive regimens.
  2. Recent (within 1 month) participation in another clinical trial that would confound the results of this study.
  3. 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 Rhythm prior to enrollment.
  4. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders 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 Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 in subjects with no significant neurocognitive deficits.
  6. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the last month, again in patients without evidence of significant neurocognitive impairment.
  7. Current, clinically significant pulmonary, cardiac, or oncologic disease, if these were severe enough to interfere with the study and/or would confound the results. Any such patients should be discussed with the sponsor prior to inclusion.
  8. History of significant liver disease or liver injury, or current liver assessment for a cause of abnormal liver tests [as indicated by abnormal liver function tests, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or serum bilirubin (> 1.5 x upper limit of normal (ULN) for any of these tests)] for an etiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of hepatic cirrhosis will be exclusionary, but the presence of NAFLD would not be exclusionary.
  9. History or presence of impaired renal function as indicated by clinically significant abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by the Cockroft Gault equation < 30 mL/min (Appendix 0).
  10. History or close family history (parents or siblings) of skin cancer or melanoma, or patient history of ocular-cutaneous albinism.
  11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions, determined as part of a screening comprehensive skin evaluation performed by a qualified dermatologist. 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. Volunteer 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. Significant hypersensitivity to study drug.
  15. Inability to comply with QD injection regimen.
  16. Females who are breastfeeding or nursing.

Inclusion criteria for extensions after 3 months of treatment:

  1. Patient completes the initial ~3 months of treatment period without evidence of severe or clinically relevant adverse events, changes in vital signs, or changes in safety laboratories or ECGs
  2. Patient loses ~5 kg (or 5% if baseline body weight < 100 kg) of weight over the treatment period.

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

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Contact: Sarah Pilley 857-264-4281

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United States, California
Axis Clinical Trials Headquarters Recruiting
Los Angeles, California, United States, 90036
Contact: Elianet De La Cruz    310-289-8242 ext 165      
Principal Investigator: Lydie Hazan         
Axis Clinical Trials-Downtown Recruiting
Los Angeles, California, United States
Contact: Sylvia Orellana    213-484-0180      
Principal Investigator: Patrick Clark         
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Hoda Farajpour, MD    720-848-5596   
Principal Investigator: Neda Rasouli, MD         
United States, Florida
University of Florida College of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Beverly Giordano    352-294-5280   
Principal Investigator: Jennifer Miller, MD         
United States, Maryland
NIH Hatfield Clinical Research Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Sheila Brady    301-451-3783   
Principal Investigator: Jack A Yanovski, MD         
United States, Nevada
Impact Clinical Trials Recruiting
Las Vegas, Nevada, United States, 89106
Contact: Fabiola Vazquez    702-889-0061      
Principal Investigator: Constance Brown         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029-6574
Contact: Jeanine Albu   
Principal Investigator: Deena Adimoolam         
United States, North Carolina
Wake Research Inc. Recruiting
Raleigh, North Carolina, United States, 27612
Contact: Kim Jolly    919-781-2514      
Principal Investigator: Wayne Harper         
United States, Pennsylvania
Obesity Institute, Geisinger Clinic Recruiting
Danville, Pennsylvania, United States, 17822
Contact: Marianne Yohn    570-214-1004   
Principal Investigator: Christopher Still, MD         
United States, Tennessee
Le Bonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38103
Contact: Raquel Mack         
Contact    901-   
Principal Investigator: Joan Han, MD         
Vanderbilt University School of Medicine Not yet recruiting
Nashville, Tennessee, United States, 37212-3157
Contact: Bethany Oates    615-322-8068   
Principal Investigator: Ashley Shoemaker         
United States, Wisconsin
Marshfield Clinic Recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Kristina Fletty         
Principal Investigator: Robert M Haws, MD         
Universidad Autónoma de Madrid Not yet recruiting
Madrid, Spain, 65 28009
Principal Investigator: Jesús Argente         
United Kingdom
Marshfield Clinic Recruiting
Birmingham, United Kingdom, B152TH
Contact: Vishy Veeranna    44 (0) 121 371 6694   
Principal Investigator: Tarekegn Hiwot, MD         
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
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Study Chair: Murray Stewart Rhythm Pharmaceuticals, Inc.

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Responsible Party: Rhythm Pharmaceuticals, Inc. Identifier: NCT03013543     History of Changes
Other Study ID Numbers: RM-493-014
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018

Keywords provided by Rhythm Pharmaceuticals, Inc.:
POMC deficiency obesity
LepR deficiency obesity
Bardet-Biedl syndrome
Alström Syndrome
Smith-Magenis Syndrome

Additional relevant MeSH terms:
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Genetic Diseases, Inborn
Nutrition Disorders
Chronobiology Disorders
Nervous System Diseases
Chromosome Disorders
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Eye Diseases, Hereditary
Eye Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Smith-Magenis Syndrome
Bardet-Biedl Syndrome
Laurence-Moon Syndrome
Alstrom Syndrome
Pathologic Processes
Body Weight
Signs and Symptoms
Abnormalities, Multiple
Congenital Abnormalities
Retinitis Pigmentosa