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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.
 
ClinicalTrials.gov Identifier: NCT03013543
Recruitment Status : Recruiting
First Posted : January 6, 2017
Last Update Posted : September 19, 2019
Sponsor:
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 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.genetic mutations.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
Criteria

Inclusion Criteria:

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

    1. POMC/PCSK1/LEPR heterozygous
    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
    4. Smith-Magenis Syndrome (SMS)
    5. SH2B1 deficiency obesity
    6. Chromosomal rearrangement of the 16p11.2 locus causing obesity
    7. CPE compound heterozygous or homozygous deficiency obesity
    8. Leptin deficiency obesity with loss of response to metreleptin.
    9. SRC1 deficiency obesity
    10. MC4R deficiency obesity

    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 12 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 12 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 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.
  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 enrolled 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: 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 ClinicalTrials.gov identifier (NCT number): NCT03013543


Contacts
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Contact: Sarah Pilley 857-264-4281 spilley@rhythmtx.com

Locations
Hide Hide 23 study locations
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United States, Arizona
Honor Health Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Principal Investigator: Janes Swain         
United States, California
Axis Clinical Trials Headquarters Recruiting
Los Angeles, California, United States, 90036
Contact: Jose Melendez-Landa    310-289-8242    jose@axistoday.com   
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    hoda.farajpour@ucdenver.edu   
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    bgiordano@ufl.edu   
Principal Investigator: Jennifer Miller, MD         
United States, Maine
Maine Medical Partners Not yet recruiting
Portland, Maine, United States, 04102
Principal Investigator: Mike Dedekian         
United States, Maryland
NIH Hatfield Clinical Research Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Sheila Brady    301-451-3783    bradys@mail.nih.gov   
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
AXIS Clinical Trials Recruiting
Brooklyn, New York, United States, 11201
Contact: Karina Betances    516-545-0951    karina@nycclinicaltrials.com   
Principal Investigator: Christian Mayaud         
University of Buffalo Not yet recruiting
Buffalo, New York, United States, 14203
Contact: Amanda House       ahouse@upa.chob.edu   
Principal Investigator: Indrajit Majumdar         
AXIS Clinical Trials Recruiting
New York, New York, United States, 10022
Contact: Yannett Franklin    646-625-3011    yannett@nycclinicaltrials.com   
Principal Investigator: Vaugh Whitaker         
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029-6574
Contact: Jeanine Albu       Jeanine.AlbuMD@mountsinai.org   
Principal Investigator: Deena Adimoolam         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Kristi Romero       kristi.romero@duke.edu   
Principal Investigator: Michael Freemark         
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    mmyohn2@geisinger.edu   
Principal Investigator: Christopher Still, MD         
United States, Tennessee
Le Bonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38103
Contact: Raquel Mack         
Contact    901-    rmack7@uthsc.edu   
Principal Investigator: Joan Han, MD         
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37212-3157
Contact: Bethany Oates    615-322-8068    bethany.l.oates@vanderbilt.edu   
Principal Investigator: Ashley Shoemaker         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Sisley         
United States, Wisconsin
Marshfield Clinic Recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Kristina Fletty         
Principal Investigator: Robert M Haws, MD         
Spain
Universidad Autónoma de Madrid Recruiting
Madrid, Spain, 65 28009
Principal Investigator: Jesús Argente         
Sub-Investigator: Gabriel Angel Martos-Moreno         
Sub-Investigator: Jesus Pozo Roman         
Sub-Investigator: Amalia Tamariz Martell-Moreno         
Sub-Investigator: Angela Hernandez         
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom, B152TH
Contact: Vishy Veeranna    44 (0) 121 371 6694    Vishy.Veeranna@uhb.nhs.uk   
Principal Investigator: Tarekegn Hiwot, MD         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom, CA2 0QQ
Contact: Elana Henning    44 (0)1223 762634    eh330@medschl.cam.ac.uk   
Contact: Lynne Stanley    44 (0)1223 762634    ls824@medschl.cam.ac.uk   
Principal Investigator: Sadaf Farooqi         
Hammersmith Hospital Recruiting
London, United Kingdom, W12 0HS
Contact: Amin Alamshah    44 (0)203 3136197    amin.alamshah@nhs.net   
Contact: Aime Boakye    44 (0)203 31331312    aime.boakye@nhs.net   
Principal Investigator: Tony Goldstone         
Sub-Investigator: Nicola Bridges         
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
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Study Chair: Murray Stewart Rhythm Pharmaceuticals, Inc.

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Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03013543    
Other Study ID Numbers: RM-493-014
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
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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Smith-Magenis Syndrome
Bardet-Biedl Syndrome
Laurence-Moon Syndrome
Alstrom Syndrome
Genetic Diseases, Inborn
Obesity
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Chronobiology Disorders
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Retinitis Pigmentosa
Eye Diseases, Hereditary
Eye Diseases
Ciliopathies
Hereditary Sensory and Motor Neuropathy
Nervous System Malformations
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases