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Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Patients With Moderate to Severe Obesity

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ClinicalTrials.gov Identifier: NCT03746522
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.

Brief Summary:
This pivotal, phase 3 study is designed to confirm the efficacy and safety of setmelanotide, a potent melanocortin receptor type 4 (MC4R) agonist, for the treatment of obesity and hyperphagia in patients with Bardet Biedl syndrome (BBS) or Alström syndrome (AS). The study's primary efficacy endpoint will evaluate the proportion of patients (≥12 years of age at baseline) who lose ≥10% of their baseline body weight following approximately (~) 52 weeks of treatment with setmelanotide compared to a historical control rate. The study will consist of 3 treatment periods. Eligible patients will enter a 14 week, randomized, double-blind, placebo-controlled treatment period (Period 1) that will be followed by a 38 week open label treatment period (Period 2) in which all patients will receive setmelanotide. The primary analysis will be performed after Period 2. Following Period 2, patients will continue open-label treatment for 14 weeks (Period 3) after which they may be enrolled into a separate treatment extension study.

Condition or disease Intervention/treatment Phase
Bardet Biedl Syndrome (BBS) Alström Syndrome (AS) Drug: Setmelanotide Drug: Placebos Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Trial of Setmelanotide (RM-493), a Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Patients With Moderate to Severe Obesity
Actual Study Start Date : December 10, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020


Arm Intervention/treatment
Experimental: Setmelanotide
Dosage form: Subcutaneous injection Dosage: 3 mg Frequency: daily
Drug: Setmelanotide
Setmelanotide is a peptide that binds to the human MC4 receptor.
Other Name: SET

Placebo Comparator: Placebo
Dosage form: Subcutaneous injection Dosage: 3 mg equivalent volume Frequency: daily
Drug: Placebos
Matching placebo at equivalent volume to 3 mg setmelanotide.




Primary Outcome Measures :
  1. Effect of Setmelanotide [ Time Frame: 52 weeks ]
    The proportion of patients (greater than or equal to 12 years of age at baseline) who achieve a greater than or equal to 10% reduction from baseline in body weight (ie, are 'responders') after ~52 weeks of treatment with setmelanotide.



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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. BBS clinical diagnosis as per Beales, 1999 (with either 4 primary features or 3 primary and 2 secondary features) Or AS diagnosis as per Marshall, 2007 (using major and minor age adjusted criteria).
  2. Greater than or equal to ≥6 years of age.
  3. Obese, defined as BMI ≥30 kg/m2 for patients ≥16 years of age or weight >97th percentile for age and sex on growth chart assessment for patients 6 to 15 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), 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 use a double barrier method contraception if they become sexually active during the study or within 90 days following their participation in the study. Male patients must also 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. These patients may be reconsidered approximately 1 month after cessation of such intensive regimens.
  2. Current or prior (within prior 2 months) use of any medication, including those approved to treat obesity, that could impact the efficacy results of this study (eg, orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, liraglutide). Patients on a stable dose and regimen (for at least 2 months) of medication to treat attention deficit hyperactivity disorder (ADHD) may be enrolled in the study as long as they agree to remain on the same dose and regimen during the 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, resulted in <10% weight loss compared to pre-operative baseline weight, or there is 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 Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V) 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. In patients with no significant neurocognitive deficits:

    • A PHQ-9 score of ≥15 and/or
    • Any suicidal ideation of type 4 or 5 on the 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 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. History of significant liver disease or liver injury, or a current liver assessment due to abnormal liver tests (as indicated by abnormal liver function tests, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin >1.5x the 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 is exclusionary, but the presence of NAFLD is not be exclusionary.
  8. Moderate to severe renal dysfunction defined as <30 mL/min (Appendix 11.6).
  9. History or close family history (parents or siblings) of skin cancer or melanoma (excluding non-invasive basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.
  10. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of comprehensive skin evaluation performed by a qualified dermatologist during screening. Any concerning lesions identified during the screening period will be biopsied and results must be known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient should be excluded from the study.
  11. Patient 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): NCT03746522


Contacts
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Contact: Matthew Webster 8572544105 mwebster@rhythmtx.com

Locations
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United States, California
Wr-McCr, Llc Recruiting
San Diego, California, United States, 92108
Contact: Nicolle Mendez    619-521-2830    nkmendez@mccresearch.com   
Principal Investigator: Laurie Han-Conrad         
United States, Massachusetts
UMMS Baystate Health; BAYSTATE MEDICAL CENTER; Baystate Children's Specialty Center Recruiting
Springfield, Massachusetts, United States, 01199
Contact: Victoria R Cobb    413-794-1466    Victoria.Cobb@baystatehealth.org   
Principal Investigator: Rushika Conroy         
United States, New York
Columbia University Center Recruiting
New York, New York, United States, 10032
Contact: Joane Carroll    212-305-5508    jc688@cumc.columbia.edu   
United States, North Carolina
M3 Wake Research Recruiting
Raleigh, North Carolina, United States, 27612
Contact: Lucie Mangala    919-781-2514    lmangala@wakeresearch.com   
Contact: Bridget Smallwood-Hurdle    919-645-9229    bsmallwood-hurdle@wakeresearch.com   
Principal Investigator: Wayne Harper         
United States, Tennessee
University of Tennessee Health Science Center Recruiting
Memphis, Tennessee, United States, 38103
Contact: Jennifer Ferrell Ferrell    901-287-5817    jferre12@uthsc.edu   
Contact: Raquel Mack    901-287-6869    rmack7@uthsc.edu   
Principal Investigator: Joan Han         
United States, Wisconsin
Marshfield Clinic Research Foundation Recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Lauren Putnam    715-389-4472    putnam.lauren@marshfieldresearch.org   
Contact: Thomas Rose    715-389-4467    rose.thomas@marshfieldresearch.org   
Principal Investigator: Robert Haws         
Canada, Alberta
Alberta Health Services Recruiting
Edmonton, Alberta, Canada, T6G 2E1
Contact: Caroline Lyster    780.248.1770      
Contact       clyster@ualberta.ca   
Puerto Rico
UPR Medical Sciences Campus Recruiting
Rio Piedras, Puerto Rico, 00935
Contact: Janice Diaz    (787) 759-0306    janice.diaz2@upr.edu   
Principal Investigator: Maribel Campos-Rivera         
Spain
Universidad Autónoma de Madrid University Hospital Niño Recruiting
Madrid, Spain, 28009
Contact: Nuria Ventosillo       Nuria.ventosillo@salud.madrid.org   
Principal Investigator: Jesús Argente         
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
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Study Chair: Murray Stewart, MD Rhythm Pharmceuticals, Inc

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Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03746522     History of Changes
Other Study ID Numbers: RM-493-023
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019

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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.:
MC4R Pathway
Obesity
BBS
AS
Additional relevant MeSH terms:
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Bardet-Biedl Syndrome
Laurence-Moon Syndrome
Alstrom Syndrome
Obesity
Obesity, Morbid
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Retinitis Pigmentosa
Eye Diseases, Hereditary
Eye Diseases
Ciliopathies
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Hereditary Sensory and Motor Neuropathy
Nervous System Malformations
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases