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Setmelanotide for the Treatment of Early-Onset POMC Deficiency Obesity

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ClinicalTrials.gov Identifier: NCT02896192
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : August 15, 2018
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 and other factors in patients with pro-opiomelanocortin (POMC) deficiency obesity due to rare bi-allelic loss-of function POMC or PCSK1 genetic mutations.

Condition or disease Intervention/treatment Phase
Pro-opiomelanocortin (POMC) Deficiency Obesity Drug: Setmelanotide Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of RM-493, a MC4R Agonist, in Early Onset POMC Deficiency Obesity Due to Bi-Allelic Loss-of-Function POMC or PCSK1 Genetic Mutation
Actual Study Start Date : February 14, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : October 2019


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

Placebo Comparator: Placebo
Placebo subcutaneous injection once daily
Drug: Placebo
During the double blind placebo withdrawal period, patients will receive RM-493 or placebo at variable times over an 8 week period in order for patients to serve as their own control.




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. Improvements in insulin resistance [ Time Frame: 1 year ]
    Assessment of fasting glucose, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT).

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

  6. 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



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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. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC or PCSK1 genes, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype.
  2. Age 12 years and above.
  3. If adult age ≥18 years, obesity with body mass index (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 be able to understand and sign the written informed consent/assent.
  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) or post-menopausal for at least 12 months (and confirmed with a screening FSH level in the post-menopausal lab range), 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, 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.
  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 (Appendix 11.10).
  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.

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): NCT02896192


Contacts
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Contact: Hillori Connors 857-264-4280 hconnors@rhythmtx.com

Locations
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United States, Arizona
Honor Health Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: James Swain, MD    480-882-7460    james.swain@honorhealth.com   
Principal Investigator: James Swain, MD         
Belgium
UZ Gent Recruiting
Gent, Belgium, 9000
Contact: Kathleen De Waele, MD    32 9 332 4825    Kathleen.dewaele@uzgent.be   
Principal Investigator: Kathleen De Waele, MD         
Canada, Ontario
Peel Memorial Hospital Recruiting
Brampton, Ontario, Canada, L6W 2Z8
Contact: Karlee Trafford       karlee.trafford@illingworthresearch.com   
Principal Investigator: Allison Bahm, MD         
France
Institute of Cardiometabolism and Nutrition / Pitié-Salpêtrière Hospital Recruiting
Paris, France, 75013
Contact: Karine Clement, MD, PhD       karine.clement@aphp.fr   
Germany
Charite Campus Virchow-Klinikum / Institute for Experimental Paediatric Endocrinology Recruiting
Berlin, Germany, 13353
Contact: Peter Kuhnen, MD       Peter.Kuehnen@charite.de   
Spain
Universidad Autonoma de Madrid University Hospital Nino Jesus Not yet recruiting
Madrid, Spain, 28009
Contact: Naciba Zetchi       nzetchi@rhythmtx.com   
Principal Investigator: Jesus Argente, MD         
Principal Investigator: Gabriel A Martos Moreno, MD         
United Kingdom
University of Cambridge Metabolic Research Laboratories Not yet recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Sadaf Farooqi, PhD FRCP FMedSci       isf20@medschl.cam.ac.uk   
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
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Study Chair: Liz Stoner Rhythm Pharmceuticals, Inc.

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Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02896192     History of Changes
Other Study ID Numbers: RM-493-012
First Posted: September 12, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhythm Pharmaceuticals, Inc.:
POMC deficiency obesity
PCSK1 deficiency obesity

Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms