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EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

Primary Purpose

Obesity, Genetic Obesity

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Setmelanotide
Placebo
Sponsored by
Rhythm Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia, POMC, PCSK1, LEPR, SH2B1, NCOA1 (SRC1)

Eligibility Criteria

6 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Phoenix Children's HospitalRecruiting
  • HonorHealth Bariatric CenterRecruiting
  • Children's Hospital Los AngelesRecruiting
  • Children's Hospital ColoradoRecruiting
  • Yale Center for Clinical InvestigationRecruiting
  • Advent HealthRecruiting
  • InQuest Medical ResearchRecruiting
  • UMASS Memorial Medical CenterRecruiting
  • University of MichiganRecruiting
  • Metro Detroit Endocrinology CenterRecruiting
  • Mayo ClinicRecruiting
  • St. Luke's HospitalRecruiting
  • Washington University in St. LouisRecruiting
  • University of BuffaloRecruiting
  • Metropolitan Hospital CenterRecruiting
  • Mount Sinai HospitalRecruiting
  • Columbia UniversityRecruiting
  • Ten's Medical Center - Pediatric Endocrinology ClinicRecruiting
  • Cincinnati Children's Hospital Medical CenterRecruiting
  • Oregon Health & Science UniversityRecruiting
  • Geisinger ClinicRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • UPMC MontefioreRecruiting
  • Vanderbilt University School of MedicineRecruiting
  • Texas TechRecruiting
  • Texas Children's HospitalRecruiting
  • Biopharma InformaticRecruiting
  • Rio Grande Valley Endocrine CenterRecruiting
  • Endocrine Associates of Dallas and PlanoRecruiting
  • MultiCare Health System Institute for Research and InnovationRecruiting
  • West Virginia UniversityRecruiting
  • Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, IncRecruiting
  • University of Alberta - Alberta Diabetes Institute (ADI)Recruiting
  • GH Est Hopital Femme Mere EnfantRecruiting
  • Hopital Armand TrousseauRecruiting
  • Hu Pitie Salpetriere AphpRecruiting
  • Centre Hospitalier Universitaire (CHU) de BordeauxRecruiting
  • Hôpital Félix Guyon BellepierreRecruiting
  • Charite - Universitatsmedizin BerlinRecruiting
  • Endokrinologikum FrankfurtRecruiting
  • Universitaetsklinikum LeipzigRecruiting
  • Universitaetsklinikum UlmRecruiting
  • University of Patras School of MedicineRecruiting
  • Hasharon HospitalRecruiting
  • Chaim Sheba MC, Safra Children's HospitalRecruiting
  • Erasmus Medisch CentrumRecruiting
  • University of Puerto RicoRecruiting
  • Hospital Sant Joan de Deu, BarcelonaRecruiting
  • Hospital Fundación Jimenez DíazRecruiting
  • Hospital Universitario Virgen de la Victoria de MálagaRecruiting
  • Hospital General de ValenciaRecruiting
  • Bristol Royal Hospital for ChildrenRecruiting
  • University of CambridgeRecruiting
  • Aintree University HospitalRecruiting
  • London Medical - The London Diabetes CentreRecruiting
  • University College London Hospitals NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

POMC or PCSK1 variant

LEPR variant

NCOA1 (SRC1) variant

SH2B1 variant

Arm Description

1:1 Randomization

1:1 Randomization

1:1 Randomization

1:1 Randomization

Outcomes

Primary Outcome Measures

Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI

Secondary Outcome Measures

The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo
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
The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo
The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo

Full Information

First Posted
September 30, 2021
Last Updated
May 26, 2023
Sponsor
Rhythm Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05093634
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 10, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rhythm Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Genetic Obesity
Keywords
Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia, POMC, PCSK1, LEPR, SH2B1, NCOA1 (SRC1)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
POMC or PCSK1 variant
Arm Type
Experimental
Arm Description
1:1 Randomization
Arm Title
LEPR variant
Arm Type
Experimental
Arm Description
1:1 Randomization
Arm Title
NCOA1 (SRC1) variant
Arm Type
Experimental
Arm Description
1:1 Randomization
Arm Title
SH2B1 variant
Arm Type
Experimental
Arm Description
1:1 Randomization
Intervention Type
Drug
Intervention Name(s)
Setmelanotide
Intervention Description
Subcutaneous Injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous Injection
Primary Outcome Measure Information:
Title
Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI
Time Frame
Baseline to 52 weeks
Secondary Outcome Measure Information:
Title
The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo
Time Frame
Baseline to 52 weeks
Title
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
Time Frame
Baseline to 52 weeks
Title
The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo
Time Frame
Baseline to 52 weeks
Title
The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo
Time Frame
Baseline to 52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rhythm Clinical Trials
Phone
(857) 264-4280
Email
clinicaltrials@rhythmtx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Physician Inquiry: Clinical Trials
Phone
(857) 264-4280
Email
clinicaltrials@rhythmtx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Meeker, MD
Organizational Affiliation
Rhythm Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Individual Site Status
Recruiting
Facility Name
HonorHealth Bariatric Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
Yale Center for Clinical Investigation
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
Facility Name
Advent Health
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32701
Country
United States
Individual Site Status
Recruiting
Facility Name
InQuest Medical Research
City
Suwanee
State/Province
Georgia
ZIP/Postal Code
30024
Country
United States
Individual Site Status
Recruiting
Facility Name
UMASS Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Individual Site Status
Recruiting
Facility Name
Metro Detroit Endocrinology Center
City
Dearborn
State/Province
Michigan
ZIP/Postal Code
48126-2619
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Individual Site Status
Recruiting
Facility Name
St. Luke's Hospital
City
Chesterfield
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14260
Country
United States
Individual Site Status
Recruiting
Facility Name
Metropolitan Hospital Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Ten's Medical Center - Pediatric Endocrinology Clinic
City
Staten Island
State/Province
New York
ZIP/Postal Code
10306
Country
United States
Individual Site Status
Recruiting
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Name
Geisinger Clinic
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
UPMC Montefiore
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Name
Vanderbilt University School of Medicine
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Tech
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Biopharma Informatic
City
Houston
State/Province
Texas
ZIP/Postal Code
77084
Country
United States
Individual Site Status
Recruiting
Facility Name
Rio Grande Valley Endocrine Center
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Individual Site Status
Recruiting
Facility Name
Endocrine Associates of Dallas and Plano
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Individual Site Status
Recruiting
Facility Name
MultiCare Health System Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Individual Site Status
Recruiting
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Individual Site Status
Recruiting
Facility Name
Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, Inc
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Alberta - Alberta Diabetes Institute (ADI)
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
Individual Site Status
Recruiting
Facility Name
GH Est Hopital Femme Mere Enfant
City
Lyon
ZIP/Postal Code
69677
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Armand Trousseau
City
PARIS Cedex 12
ZIP/Postal Code
75771
Country
France
Individual Site Status
Recruiting
Facility Name
Hu Pitie Salpetriere Aphp
City
Paris
ZIP/Postal Code
75651
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire (CHU) de Bordeaux
City
Pessac
ZIP/Postal Code
33604
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Félix Guyon Bellepierre
City
Saint-Denis
ZIP/Postal Code
97400
Country
France
Individual Site Status
Recruiting
Facility Name
Charite - Universitatsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Recruiting
Facility Name
Endokrinologikum Frankfurt
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Patras School of Medicine
City
Rio
ZIP/Postal Code
26504
Country
Greece
Individual Site Status
Recruiting
Facility Name
Hasharon Hospital
City
Petah Tikva
ZIP/Postal Code
49372
Country
Israel
Individual Site Status
Recruiting
Facility Name
Chaim Sheba MC, Safra Children's Hospital
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Individual Site Status
Recruiting
Facility Name
Erasmus Medisch Centrum
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
University of Puerto Rico
City
San Juan
ZIP/Postal Code
00925-253
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Name
Hospital Sant Joan de Deu, Barcelona
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Fundación Jimenez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen de la Victoria de Málaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital General de Valencia
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Individual Site Status
Recruiting
Facility Name
Bristol Royal Hospital for Children
City
Bristol
ZIP/Postal Code
BS2 8AE
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University of Cambridge
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Aintree University Hospital
City
Liverpool
ZIP/Postal Code
L9 7AL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
London Medical - The London Diabetes Centre
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
WC1E6JF
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

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