Clinical trial NCT05093634: EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Obesity
Genetic Obesity
Keywords: Melanocortin-4 Receptor Pathway
Genetic Obesity
Hunger
Hyperphagia
POMC
PCSK1
LEPR
SH2B1
NCOA1 (SRC1)
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-26
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI
timeFrame: Baseline to 52 weeks
Secondary outcomes:
measure: The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo
timeFrame: Baseline to 52 weeks
measure: 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
timeFrame: Baseline to 52 weeks
measure: The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo
timeFrame: Baseline to 52 weeks
measure: The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo
timeFrame: Baseline to 52 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Bariatric Center
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation
state: Connecticut
city: Altamonte Springs
country: United States
facility: Advent Health
state: Florida
city: Suwanee
country: United States
facility: InQuest Medical Research
state: Georgia
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Dearborn
country: United States
facility: Metro Detroit Endocrinology Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Buffalo
country: United States
facility: University of Buffalo
state: New York
city: New York
country: United States
facility: Metropolitan Hospital Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Staten Island
country: United States
facility: Ten's Medical Center - Pediatric Endocrinology Clinic
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Montefiore
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic
state: Texas
city: McAllen
country: United States
facility: Rio Grande Valley Endocrine Center
state: Texas
city: Plano
country: United States
facility: Endocrine Associates of Dallas and Plano
state: Texas
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, Inc
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta - Alberta Diabetes Institute (ADI)
state: Alberta
city: Lyon
country: France
facility: GH Est Hopital Femme Mere Enfant
city: PARIS Cedex 12
country: France
facility: Hopital Armand Trousseau
city: Paris
country: France
facility: Hu Pitie Salpetriere Aphp
city: Pessac
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux
city: Saint-Denis
country: France
facility: Hôpital Félix Guyon Bellepierre
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Frankfurt
country: Germany
facility: Endokrinologikum Frankfurt
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Rio
country: Greece
facility: University of Patras School of Medicine
city: Petah Tikva
country: Israel
facility: Hasharon Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba MC, Safra Children's Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu, Barcelona
city: Madrid
country: Spain
facility: Hospital Fundación Jimenez Díaz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria de Málaga
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: University of Cambridge
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: London
country: United Kingdom
facility: London Medical - The London Diabetes Centre
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References: