Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity

Phase 2

Completed

Conditions: Genetic Obesity
Obesity
Obesity Due to Melanocortin 4 Receptor Deficiency

Interventions: Drug: Setmelanotide

Registration Number: NCT03013543

Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Brief Summary: The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 213

Inclusion Criteria

Participants with the following genotypes and/or clinical assessment:
1. POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants
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. SMS
5. SH2B1 deficiency obesity
6. Chromosomal rearrangement of the 16p11.2 locus causing obesity
7. Carboxypeptidase E (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
Age 6 years and above
Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age.
Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study.

Key

Exclusion Criteria

Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in > 2% weight loss.
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).
Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
Suicidal ideation, attempt or behavior
Clinically significant pulmonary, cardiac, or oncologic disease
hemoglobin A1c (HbA1c) > 9.0% at Screening
History of significant liver disease
Glomerular filtration rate (GFR) < 30 milliliter/minute (mL/min) at Screening.
History or close family history of melanoma or participant history of oculocutaneous albinism
Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
Inability to comply with QD injection regimen.
Females who are breastfeeding or nursing.

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
16p11.2 Cohort	Setmelanotide	Participants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
MC4R Cohort	Setmelanotide	Participants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
POMC/PCSK1/LEPR Composite Heterozygous Cohort	Setmelanotide	Participants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
POMC/PCSK1/LEPR Heterozygous Cohort	Setmelanotide	Participants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
POMC/PCSK1/LEPR Compound Heterozygous Cohort	Setmelanotide	Participants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
SH2B1 Cohort	Setmelanotide	Participants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
SRC1 Cohort	Setmelanotide	Participants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
SMS Cohort	Setmelanotide	Participants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
AS Cohort	Setmelanotide	Participants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
BBS Cohort	Setmelanotide	Participants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Primary Outcome Measures

Name	Time	Method
Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment	Baseline to Month 3

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From first dose up to Month 16	An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAEs were defined as AEs reported after dosing on Day 1.
Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment	Baseline, Month 3
Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment	Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years	Baseline, Month 3	The mean change in daily hunger questionnaire scores for participants ≥ 12 years of age with obesity in treatment with setmelanotide was evaluated. On the Daily Hunger Questionnaire, each of the 3 items (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) was assessed daily and scored separately using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible.
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years	Baseline, Month 3	The mean change in daily hunger questionnaire scores for participants \< 12 years of age with obesity in treatment with setmelanotide was evaluated. Hunger was assessed daily using a Daily Hunger Questionnaire with a pictorial (smiley face) version of the Likert rating scale with scores ranged from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible.
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years	Baseline, Month 3	For participants ≥ 12 years of age, the following question was asked using the Global Hunger Questionnaire: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; Severe hunger; and Not answered.
Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment	Baseline, Month 3	Waist circumference (cm) was measured according to the National Heart, Lung, and Blood Institute (NHLBI) criteria. All measurements were single measures. Waist circumference was measured when participants were in fasting condition and at approximately the same time at each visit.
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years	Baseline, Month 3	For participants \< 12 years of age, the following question was asked to parents or caregivers of participants using the Global Hunger Questionnaire: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; Extremely hungry; and Not answered.

Trial Locations

Locations (57): AXIS South Florida Clinical Trials
🇺🇸
Hialeah, Florida, United States
Synexus Clinical Research US, Inc. - Akron
🇺🇸
Akron, Ohio, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Seattle Children's Research Institute
🇺🇸
Seattle, Washington, United States
San Diego Wake Research
🇺🇸
San Diego, California, United States
Impact Clinical Trials
🇺🇸
Las Vegas, Nevada, United States
Synexus Clinical Research US, Inc. - Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Synexus Clinical Research US, Inc. - San Antonio
🇺🇸
San Antonio, Texas, United States
Vanderbilt University School of Medicine
🇺🇸
Nashville, Tennessee, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC
🇺🇸
Birmingham, Alabama, United States
Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Obesity Institute, Geisinger Clinic
🇺🇸
Danville, Pennsylvania, United States
Axis Clinical Trials-Downtown
🇺🇸
Los Angeles, California, United States
Axis Clinical Trials Headquarters
🇺🇸
Los Angeles, California, United States
Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon
🇫🇷
Saint-Denis, France
Synexus Clinical Research US, Inc. - Columbus
🇺🇸
Columbus, Ohio, United States
Synexus Clinical Research US, Inc. - Plano
🇺🇸
Plano, Texas, United States
AXIS New York Clinical Trials
🇺🇸
Brooklyn, New York, United States
Synexus Clinical Research US, Inc. - Chicago
🇺🇸
Chicago, Illinois, United States
Maine Medical Partners
🇺🇸
Portland, Maine, United States
Synexus Clinical Research US, Inc. - St. Petersburg
🇺🇸
Pinellas Park, Florida, United States
Columbia University
🇺🇸
New York, New York, United States
Wake Research Inc.
🇺🇸
Raleigh, North Carolina, United States
Synexus Clinical Research US, Inc. - Primary Care Associates, PC
🇺🇸
Anderson, South Carolina, United States
Erasmus MC
🇳🇱
Rotterdam, Netherlands
University Hospitals Birmingham NHS Foundation Trust
🇬🇧
Birmingham, United Kingdom
Le Bonheur Children's Hospital
🇺🇸
Memphis, Tennessee, United States
Hospital Infantil Universitario Niño Jesús
🇪🇸
Madrid, Spain
University of Alberta
🇨🇦
Edmonton, Canada
Hopital Trousseau - Nutrition et Gastroentérologie
🇫🇷
Paris, France
Hopital de la Pitié-Salpêtrière
🇫🇷
Paris, France
Marshfield Clinic Research Institute
🇺🇸
Marshfield, Wisconsin, United States
Addenbrooke's Hospital
🇬🇧
Cambridge, United Kingdom
Hammersmith Hospital
🇬🇧
London, United Kingdom
Charité Berlin
🇩🇪
Berlin, Germany
University of Leipzig
🇩🇪
Leipzig, Germany
Washington University St. Louis
🇺🇸
Saint Louis, Missouri, United States
AXIS Clinical Trials
🇺🇸
New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
NIH Hatfield Clinical Research Center
🇺🇸
Bethesda, Maryland, United States
Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus
🇺🇸
Aurora, Colorado, United States
Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
🇺🇸
Mesa, Arizona, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
University at Buffalo
🇺🇸
Buffalo, New York, United States
Childrens Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
University of Ulm
🇩🇪
Ulm, Germany
Synexus Clinical Research US, Inc. - Phoenix Southeast
🇺🇸
Chandler, Arizona, United States
Wake Research TN
🇺🇸
Chattanooga, Tennessee, United States
University General Hospital of Patras
🇬🇷
Río, Patras, Greece
Edmond and Lily Safra Children's Hospital
🇮🇱
Ramat Gan, Israel
Honor Health Research Institute
🇺🇸
Scottsdale, Arizona, United States
Division of Endocrinology and Diabetes Children's National Hospital
🇺🇸
Washington, District of Columbia, United States
University of Florida College of Medicine
🇺🇸
Gainesville, Florida, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
University of Michigan Medicine
🇺🇸
Ann Arbor, Michigan, United States

Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity

Recruitment & Eligibility

Study & Design

Trial Locations

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