EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
- Conditions
- Genetic ObesityObesity
- Interventions
- Drug: Placebo
- Registration Number
- NCT05093634
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway:
* POMC or PCSK1 (Sub-study 035a)
* LEPR (Sub-study 035b)
* SRC1 (Sub-study 035c)
* SH2B1 (Sub-study 035d)
The objectives and endpoints are identical for these sub-studies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 400
-
Patients must have a pre-identified:
- Heterozygous genetic variant in the POMC gene or PCSK1 gene
- Heterozygous genetic variant in the LEPR gene
- Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1)
- Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene
-
Between 6 and 65 years of age at the time of provision of informed consent/assent
-
Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age
-
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
-
Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood
-
Agree to use a highly effective form of contraception throughout the study and for 90 days following the study
-
Reported history of lifestyle intervention of diet and exercise
-
Reported history of hyperphagia
Key
- Weight loss of 2% or greater in the previous 3 months
- Recent history of bariatric surgery
- Significant psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
- Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease
- Glycated hemoglobin (HbA1C) >10% at Screening
- History of significant liver disease or severe kidney disease
- History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
- Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
- Significant hypersensitivity to any excipient in the study drug
- If female, pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NCOA1 (SRC1) variant Setmelanotide 1:1 Randomization POMC or PCSK1 variant Placebo 1:1 Randomization LEPR variant Setmelanotide 1:1 Randomization POMC or PCSK1 variant Setmelanotide 1:1 Randomization NCOA1 (SRC1) variant Placebo 1:1 Randomization SH2B1 variant Placebo 1:1 Randomization LEPR variant Placebo 1:1 Randomization SH2B1 variant Setmelanotide 1:1 Randomization
- Primary Outcome Measures
Name Time Method Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI Baseline to 52 weeks
- Secondary Outcome Measures
Name Time Method The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo Baseline to 52 weeks The difference in mean change in body weight in adult patients treated with setmelanotide compared to placebo, assessed as percent change in baseline body weight Baseline to 52 weeks The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo Baseline to 52 weeks The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo Baseline to 52 weeks
Trial Locations
- Locations (56)
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
HonorHealth Bariatric Center
🇺🇸Scottsdale, Arizona, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Yale Center for Clinical Investigation
🇺🇸New Haven, Connecticut, United States
Advent Health
🇺🇸Altamonte Springs, Florida, United States
InQuest Medical Research
🇺🇸Suwanee, Georgia, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Metro Detroit Endocrinology Center
🇺🇸Dearborn, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
St. Luke's Hospital
🇺🇸Chesterfield, Missouri, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
University of Buffalo
🇺🇸Buffalo, New York, United States
Metropolitan Hospital Center
🇺🇸New York, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Ten's Medical Center - Pediatric Endocrinology Clinic
🇺🇸Staten Island, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Geisinger Clinic
🇺🇸Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Montefiore
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
Texas Tech
🇺🇸Amarillo, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Biopharma Informatic
🇺🇸Houston, Texas, United States
Rio Grande Valley Endocrine Center
🇺🇸McAllen, Texas, United States
Endocrine Associates of Dallas and Plano
🇺🇸Plano, Texas, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, Inc
🇺🇸Marshfield, Wisconsin, United States
University of Alberta - Alberta Diabetes Institute (ADI)
🇨🇦Edmonton, Alberta, Canada
GH Est Hopital Femme Mere Enfant
🇫🇷Lyon, France
Hopital Armand Trousseau
🇫🇷PARIS Cedex 12, France
Hu Pitie Salpetriere Aphp
🇫🇷Paris, France
Centre Hospitalier Universitaire (CHU) de Bordeaux
🇫🇷Pessac, France
Hôpital Félix Guyon Bellepierre
🇫🇷Saint-Denis, France
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Endokrinologikum Frankfurt
🇩🇪Frankfurt, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
University of Patras School of Medicine
🇬🇷Rio, Greece
Hasharon Hospital
🇮🇱Petah Tikva, Israel
Chaim Sheba MC, Safra Children's Hospital
🇮🇱Ramat Gan, Israel
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
University of Puerto Rico
🇵🇷San Juan, Puerto Rico
Hospital Sant Joan de Deu, Barcelona
🇪🇸Barcelona, Spain
Hospital Fundación Jimenez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria de Málaga
🇪🇸Málaga, Spain
Hospital General de Valencia
🇪🇸Valencia, Spain
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
University of Cambridge
🇬🇧Cambridge, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, United Kingdom
London Medical - The London Diabetes Centre
🇬🇧London, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom