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

• ClinicalTrials.gov Identifier: NCT03013543
• Recruitment Status: Completed
• First Posted: January 6, 2017
• Last Update Posted: December 27, 2022
• Sponsor: Rhythm Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rhythm Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Genetic Obesity; Obesity; Obesity Due to Melanocortin 4 Receptor Deficiency	Drug: Setmelanotide	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 213 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
• Actual Study Start Date: February 10, 2017
• Actual Primary Completion Date: March 1, 2022
• Actual Study Completion Date: March 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Effect of Setmelanotide on Body Weight Reduction [ Time Frame: Baseline to 3 months ]
   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.

Secondary Outcome Measures :

1. Change and percentage change in body weight [ Time Frame: Baseline to 3 months ]
   Change and percentage change from baseline in body weight
2. Change in daily most hunger scores [ Time Frame: Baseline to 3 months ]
   Change in the weekly average of the daily hunger score from Baseline at 3 months
3. Change in waist circumference [ Time Frame: Baseline to 3 months ]
   Change from baseline in waist circumference
4. Mean percent change in BMI [ Time Frame: Baseline to 3 months ]
   Mean percent change in body mass index from baseline at 3 months
5. Mean change in BMI-Z score in patients <12 years old [ Time Frame: Baseline to 3 months ]
   Mean change in BMI-Z score from Baseline at 3 months
6. Mean change in BMI-Z score in patients ≥12 to <18 years old [ Time Frame: Baseline to 3 months ]
   Mean change in BMI-Z score in patients ≥12 to <18 years old from Baseline at 3 months

Eligibility Criteria

• 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. 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
   4. Smith-Magenis Syndrome (SMS)
   5. SH2B1 deficiency obesity
   6. Chromosomal rearrangement of the 16p11.2 locus causing obesity
   7. 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
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. Patient 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
5. Female participants of child-bearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
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.

Key Exclusion Criteria:

1. 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.
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).
3. Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
4. Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
5. Suicidal ideation, attempt or behavior
6. Clinically significant pulmonary, cardiac, or oncologic disease
7. HbA1c >9.0% at Screening
8. History of significant liver disease
9. Glomerular filtration rate (GFR) <30 mL/min at Screening.
10. History or close family history of melanoma or patient history of oculocutaneous albinism
11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
13. Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
14. Inability to comply with QD injection regimen.
15. Females who are breastfeeding or nursing.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Alabama

Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC

Birmingham, Alabama, United States, 35211

United States, Arizona

Synexus Clinical Research US, Inc. - Phoenix Southeast

Chandler, Arizona, United States, 85224

Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC

Mesa, Arizona, United States, 85206

Honor Health Research Institute

Scottsdale, Arizona, United States, 85258

United States, California

Axis Clinical Trials-Downtown

Los Angeles, California, United States, 90017

Axis Clinical Trials Headquarters

Los Angeles, California, United States, 90036

San Diego Wake Research

San Diego, California, United States, 92108

United States, Colorado

Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States, 80045

United States, District of Columbia

Division of Endocrinology and Diabetes Children's National Hospital

Washington, District of Columbia, United States, 20010

United States, Florida

University of Florida College of Medicine

Gainesville, Florida, United States, 32610

AXIS South Florida Clinical Trials

Hialeah, Florida, United States, 33016

Florida Hospital

Orlando, Florida, United States, 32804

Synexus Clinical Research US, Inc. - St. Petersburg

Pinellas Park, Florida, United States, 33781

United States, Illinois

Synexus Clinical Research US, Inc. - Chicago

Chicago, Illinois, United States, 60602

United States, Maine

Maine Medical Partners

Portland, Maine, United States, 04102

United States, Maryland

NIH Hatfield Clinical Research Center

Bethesda, Maryland, United States, 20892

United States, Massachusetts

Baystate Medical Center

Springfield, Massachusetts, United States, 01107

United States, Michigan

University of Michigan Medicine

Ann Arbor, Michigan, United States, 48105

United States, Minnesota

Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University St. Louis

Saint Louis, Missouri, United States, 63110

United States, Nevada

Impact Clinical Trials

Las Vegas, Nevada, United States, 89106

United States, New York

AXIS New York Clinical Trials

Brooklyn, New York, United States, 11201

University at Buffalo

Buffalo, New York, United States, 14203

AXIS Clinical Trials

New York, New York, United States, 10022

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10025

Columbia University

New York, New York, United States, 10032

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

Wake Research Inc.

Raleigh, North Carolina, United States, 27612

United States, Ohio

Synexus Clinical Research US, Inc. - Akron

Akron, Ohio, United States, 44311

Synexus Clinical Research US, Inc. - Cincinnati

Cincinnati, Ohio, United States, 45236

Synexus Clinical Research US, Inc. - Columbus

Columbus, Ohio, United States, 43016

United States, Pennsylvania

Obesity Institute, Geisinger Clinic

Danville, Pennsylvania, United States, 17822

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Synexus Clinical Research US, Inc. - Primary Care Associates, PC

Anderson, South Carolina, United States, 29621

United States, Tennessee

Wake Research TN

Chattanooga, Tennessee, United States, 37421

Le Bonheur Children's Hospital

Memphis, Tennessee, United States, 38103

Vanderbilt University School of Medicine

Nashville, Tennessee, United States, 37212-3157

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Synexus Clinical Research US, Inc. - Plano

Plano, Texas, United States, 75093

Synexus Clinical Research US, Inc. - San Antonio

San Antonio, Texas, United States, 78229

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

United States, Washington

Seattle Children's Research Institute

Seattle, Washington, United States, 98101

United States, Wisconsin

Marshfield Clinic Research Institute

Marshfield, Wisconsin, United States, 54449

Canada

University of Alberta

Edmonton, Canada, T6G 2E1

France

Hopital Trousseau - Nutrition et Gastroentérologie

Paris, France, 75012

Hopital de la Pitié-Salpêtrière

Paris, France, 75013

Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon

Saint-Denis, France, 97405

Germany

Charité Berlin

Berlin, Germany, 13354

University of Leipzig

Leipzig, Germany, 04103

University of Ulm

Ulm, Germany, 89075

Greece

University General Hospital of Patras

Río, Patras, Greece, 26504

Israel

Edmond and Lily Safra Children's Hospital

Ramat Gan, Israel, 52621

Netherlands

Erasmus MC

Rotterdam, Netherlands, 3015 CE

Spain

Hospital Infantil Universitario Niño Jesús

Madrid, Spain, 65 28009

United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B15 2TH

Addenbrooke's Hospital

Cambridge, United Kingdom, CB2 0QQ

Hammersmith Hospital

London, United Kingdom, W12 0NN

Hammersmith Hospital

London, United Kingdom

Sponsors and Collaborators

Rhythm Pharmaceuticals, Inc.

Investigators

• Study Chair: David Meeker, MD; Rhythm Pharmaceuticals, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Meyer JR, Krentz AD, Berg RL, Richardson JG, Pomeroy J, Hebbring SJ, Haws RM. Kidney failure in Bardet-Biedl syndrome. Clin Genet. 2022 Apr;101(4):429-441. doi: 10.1111/cge.14119.

• Responsible Party: Rhythm Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03013543
• Other Study ID Numbers: RM-493-014
• First Posted: January 6, 2017
• Last Update Posted: December 27, 2022
• Last Verified: December 2022

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

Keywords provided by Rhythm Pharmaceuticals, Inc.:

Pro-opiomelanocortin (POMC) deficiency obesity; LepR deficiency obesity; Smith-Magenis Syndrome; MC4R deficiency obesity; SRC1 deficiency obesity; SH2B1 deficiency obesity

Additional relevant MeSH terms:

Genetic Diseases, Inborn; Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight