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Trial record 1 of 1 for:    RM-493-014
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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.

Tracking Information
First Submitted Date  ICMJE January 3, 2017
First Posted Date  ICMJE January 6, 2017
Last Update Posted Date July 16, 2021
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2017)
Effect on weight loss [ Time Frame: 1 year ]
Measurement of the effect of RM-493 on weight loss.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2017)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 1 year ]
    Assessment of Adverse Events related to treatment
  • 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).
  • Effect on Hunger [ Time Frame: 1 year ]
    Assessment of hunger using a Hunger Questionnaire.
  • 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.
  • Effect on Waist Circumference [ Time Frame: 1 year ]
    Assessment of waist circumference.
  • Reversal of weight during the off treatment withdrawal phase [ Time Frame: 2 to 4 weeks ]
    Assessment of weight regain during the withdrawal phase
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
Official Title  ICMJE Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pro-opiomelanocortin (POMC) Deficiency Obesity (Heterozygous or Epigenetic)
  • Leptin Receptor Deficiency Obesity
  • Smith-Magenis Syndrome
  • Obesity Due to Melanocortin 4 Receptor Deficiency (Disorder)
Intervention  ICMJE Drug: Setmelanotide
RM-493 once daily subcutaneous injection
Other Name: RM-493
Study Arms  ICMJE Experimental: Setmelanotide
Setmelanotide subcutaneous injection once daily
Intervention: Drug: Setmelanotide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 2, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2017)
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Greece,   Israel,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03013543
Other Study ID Numbers  ICMJE RM-493-014
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rhythm Pharmaceuticals, Inc.
Study Sponsor  ICMJE Rhythm Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Murray Stewart, BM/DM Rhythm Pharmaceuticals, Inc.
PRS Account Rhythm Pharmaceuticals, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP