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Setmelanotide for the Treatment of LEPR Deficiency 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: NCT03287960
Recruitment Status : Recruiting
First Posted : September 19, 2017
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE September 14, 2017
First Posted Date  ICMJE September 19, 2017
Last Update Posted Date February 26, 2020
Actual Study Start Date  ICMJE January 30, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2017)
Weight loss [ Time Frame: 1 year ]
Percent change in body weight from baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2017)
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 1 year ]
    Assessment of Adverse Events related to treatment
  • Body Fat Mass [ Time Frame: 1 year ]
    Assessment of body composition as measured by bioelectrical impedance (BIA) or Dual-energy x-ray absorptiometry (DXA)
  • Hunger [ Time Frame: 1 year ]
    Assessment of hunger using a hunger questionnaire
  • Improvements in insulin resistance [ Time Frame: 1 year ]
    Assessment of fasting glucose, glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT)
  • Waist circumference [ Time Frame: 1 year ]
    Assessment of waist circumference
  • Reversal of weight during the double-blind placebo controlled withdrawal phase [ Time Frame: 8 weeks ]
    Assessment of weight regain during the double-blind withdrawal phase
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Setmelanotide for the Treatment of LEPR Deficiency Obesity
Official Title  ICMJE An Open Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of Setmelanotide (RM-493), a Melanocortin 4 Receptor (MC4R) Agonist, in Early Onset Leptin Receptor (LEPR) Deficiency Obesity Due to Bi-Allelic Loss-of-Function LEPR Genetic Mutation
Brief Summary This study is assessing the effect of setmelanotide (RM-493) on weight and other factors in patients with Leptin Receptor (LEPR) deficiency obesity due to rare bi-allelic loss-of-function LEPR genetic mutation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label with an 8 week Double-Blind Placebo-Controlled Withdrawal Period
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Leptin Receptor Deficiency Obesity
Intervention  ICMJE
  • Drug: setmelanotide
    Once daily subcutaneous injection
    Other Name: RM-493
  • Drug: Placebo
    During the double blind placebo withdrawal period, patients will receive RM-493 or placebo at variable times over an 8 week period
Study Arms  ICMJE
  • Experimental: setmelanotide
    setmelanotide subcutaneous injection once daily
    Intervention: Drug: setmelanotide
  • Placebo Comparator: Placebo
    Placebo subcutaneous injection once daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 15, 2017)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for the LEPR gene, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype.
  2. Age 6 years and above. 6+: Germany, Netherlands,UK 12+France
  3. If adult age ≥18 years, obesity with BMI ≥ 30 kg/m2; if child or adolescent, obesity with weight > 97th percentile for age 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 is able to understand and sign the written informed consent/assent, after being informed about the study.
  5. Female participants of child-bearing potential must 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 failure to have progressed to Tanner Stage V and/or 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 weight loss or weight stabilization. Patients may be reconsidered approximately 1 month after cessation of such intensive regimens.
  2. 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.
  3. 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.
  4. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
  5. 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.
  6. Current, severe stable restrictive or obstructive lung disease arising because of extreme obesity, evidence of significant heart failure (NYHA Class 3 or greater), 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.
  7. 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 (> 2.0 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.
  8. 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 Cockcroft Gault equation < 30 mL/min.
  9. History or close family history (parents or siblings) of skin cancer or melanoma, or patient history of ocular-cutaneous albinism.
  10. 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.
  11. Volunteer is, in the opinion of the Study Investigator, not suitable to participate in the study.
  12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  13. Significant hypersensitivity to study drug.
  14. Inability to comply with QD injection regimen.
  15. Patients who have been placed in an institution through an official or court order, as well as those who are dependent on the sponsor, Investigator or study site.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jim Murray 857-264-4289 jmurray@rhythmtx.com
Listed Location Countries  ICMJE Canada,   France,   Germany,   Netherlands,   Réunion,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03287960
Other Study ID Numbers  ICMJE RM-493-015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rhythm Pharmaceuticals, Inc.
Study Sponsor  ICMJE Rhythm Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Liz Stoner Rhythm Pharmaceuticals, Inc.
PRS Account Rhythm Pharmaceuticals, Inc.
Verification Date February 2020

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