Clinical trial NCT03013543: Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
Official title: Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genetic Obesity
Obesity
Obesity Due to Melanocortin 4 Receptor Deficiency
Keywords: Pro-opiomelanocortin (POMC) deficiency obesity
LepR deficiency obesity
Smith-Magenis Syndrome
MC4R deficiency obesity
SRC1 deficiency obesity
SH2B1 deficiency obesity
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-06
Enrollment: 213
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Age 6 years and above
3. 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.
4. 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
5. Female participants of childbearing 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 participants 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. hemoglobin A1c (HbA1c) \> 9.0% at Screening
8. History of significant liver disease
9. Glomerular filtration rate (GFR) \< 30 milliliter/minute (mL/min) at Screening.
10. History or close family history of melanoma or participant 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. Participants 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.

Primary outcomes:
measure: Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
timeFrame: Baseline to Month 3
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose up to Month 16
measure: Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
timeFrame: Baseline, Month 3
measure: Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
timeFrame: Baseline, Month 3
measure: Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
timeFrame: Baseline, Month 3
measure: Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
timeFrame: Baseline, Month 3
measure: Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
timeFrame: Baseline, Month 3
measure: Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
timeFrame: Baseline, Month 3
measure: Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment
timeFrame: Baseline, Month 3
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - Phoenix Southeast
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC
state: Arizona
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: Axis Clinical Trials-Downtown
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials Headquarters
state: California
city: San Diego
country: United States
facility: San Diego Wake Research
state: California
city: Aurora
country: United States
facility: Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus
state: Colorado
city: Washington
country: United States
facility: Division of Endocrinology and Diabetes Children's National Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Hialeah
country: United States
facility: AXIS South Florida Clinical Trials
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Pinellas Park
country: United States
facility: Synexus Clinical Research US, Inc. - St. Petersburg
state: Florida
city: Chicago
country: United States
facility: Synexus Clinical Research US, Inc. - Chicago
state: Illinois
city: Portland
country: United States
facility: Maine Medical Partners
state: Maine
city: Bethesda
country: United States
facility: NIH Hatfield Clinical Research Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medicine
state: Michigan
city: Rochester
country: United States
facility: Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Brooklyn
country: United States
facility: AXIS New York Clinical Trials
state: New York
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: New York
country: United States
facility: AXIS Clinical Trials
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Inc.
state: North Carolina
city: Akron
country: United States
facility: Synexus Clinical Research US, Inc. - Akron
state: Ohio
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Synexus Clinical Research US, Inc. - Columbus
state: Ohio
city: Danville
country: United States
facility: Obesity Institute, Geisinger Clinic
state: Pennsylvania
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Anderson
country: United States
facility: Synexus Clinical Research US, Inc. - Primary Care Associates, PC
state: South Carolina
city: Chattanooga
country: United States
facility: Wake Research TN
state: Tennessee
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Plano
country: United States
facility: Synexus Clinical Research US, Inc. - Plano
state: Texas
city: San Antonio
country: United States
facility: Synexus Clinical Research US, Inc. - San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic Research Institute
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
city: Paris
country: France
facility: Hopital Trousseau - Nutrition et Gastroentérologie
city: Paris
country: France
facility: Hopital de la Pitié-Salpêtrière
city: Saint-Denis
country: France
facility: Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon
city: Berlin
country: Germany
facility: Charité Berlin
city: Leipzig
country: Germany
facility: University of Leipzig
city: Ulm
country: Germany
facility: University of Ulm
city: Río
country: Greece
facility: University General Hospital of Patras
state: Patras
city: Ramat Gan
country: Israel
facility: Edmond and Lily Safra Children's Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References:
citation: 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.