NCT03013543

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
213

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2017

Longer than P75 for phase_2

Geographic Reach
9 countries

58 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 3, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 6, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

February 10, 2017

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2022

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

August 18, 2023

Completed
Last Updated

August 18, 2023

Status Verified

July 1, 2023

Enrollment Period

5.1 years

First QC Date

January 3, 2017

Results QC Date

July 25, 2023

Last Update Submit

July 25, 2023

Conditions

Keywords

Pro-opiomelanocortin (POMC) deficiency obesityLepR deficiency obesitySmith-Magenis SyndromeMC4R deficiency obesitySRC1 deficiency obesitySH2B1 deficiency obesity

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment

    Baseline to Month 3

Secondary Outcomes (8)

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    From first dose up to Month 16

  • Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment

    Baseline, Month 3

  • Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment

    Baseline, Month 3

  • Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years

    Baseline, Month 3

  • Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years

    Baseline, Month 3

  • +3 more secondary outcomes

Study Arms (10)

16p11.2 Cohort

EXPERIMENTAL

Participants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

AS Cohort

EXPERIMENTAL

Participants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

BBS Cohort

EXPERIMENTAL

Participants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

MC4R Cohort

EXPERIMENTAL

Participants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

POMC/PCSK1/LEPR Heterozygous Cohort

EXPERIMENTAL

Participants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

POMC/PCSK1/LEPR Composite Heterozygous Cohort

EXPERIMENTAL

Participants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

POMC/PCSK1/LEPR Compound Heterozygous Cohort

EXPERIMENTAL

Participants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

SH2B1 Cohort

EXPERIMENTAL

Participants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

SMS Cohort

EXPERIMENTAL

Participants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

SRC1 Cohort

EXPERIMENTAL

Participants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Drug: Setmelanotide

Interventions

RM-493 QD SC injection

Also known as: RM-493
16p11.2 CohortAS CohortBBS CohortMC4R CohortPOMC/PCSK1/LEPR Composite Heterozygous CohortPOMC/PCSK1/LEPR Compound Heterozygous CohortPOMC/PCSK1/LEPR Heterozygous CohortSH2B1 CohortSMS CohortSRC1 Cohort

Eligibility Criteria

Age6 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Participants with the following genotypes and/or clinical assessment:
  • POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants
  • POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
  • POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity
  • SMS
  • SH2B1 deficiency obesity
  • Chromosomal rearrangement of the 16p11.2 locus causing obesity
  • Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity
  • Leptin deficiency obesity with loss of response to metreleptin
  • SRC1 deficiency obesity
  • MC4R deficiency obesity
  • Age 6 years and above
  • 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.
  • 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
  • Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
  • +1 more criteria

You may not qualify if:

  • 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.
  • 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).
  • Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in \>10% weight loss durably maintained
  • Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
  • Suicidal ideation, attempt or behavior
  • Clinically significant pulmonary, cardiac, or oncologic disease
  • hemoglobin A1c (HbA1c) \> 9.0% at Screening
  • History of significant liver disease
  • Glomerular filtration rate (GFR) \< 30 milliliter/minute (mL/min) at Screening.
  • History or close family history of melanoma or participant history of oculocutaneous albinism
  • Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
  • Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  • Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
  • Inability to comply with QD injection regimen.
  • Females who are breastfeeding or nursing.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (58)

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

Birmingham, Alabama, 35211, United States

Location

Synexus Clinical Research US, Inc. - Phoenix Southeast

Chandler, Arizona, 85224, United States

Location

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

Mesa, Arizona, 85206, United States

Location

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Axis Clinical Trials-Downtown

Los Angeles, California, 90017, United States

Location

Axis Clinical Trials Headquarters

Los Angeles, California, 90036, United States

Location

San Diego Wake Research

San Diego, California, 92108, United States

Location

Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Division of Endocrinology and Diabetes Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

AXIS South Florida Clinical Trials

Hialeah, Florida, 33016, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

Synexus Clinical Research US, Inc. - St. Petersburg

Pinellas Park, Florida, 33781, United States

Location

Synexus Clinical Research US, Inc. - Chicago

Chicago, Illinois, 60602, United States

Location

Maine Medical Partners

Portland, Maine, 04102, United States

Location

NIH Hatfield Clinical Research Center

Bethesda, Maryland, 20892, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01107, United States

Location

University of Michigan Medicine

Ann Arbor, Michigan, 48105, United States

Location

Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Impact Clinical Trials

Las Vegas, Nevada, 89106, United States

Location

AXIS New York Clinical Trials

Brooklyn, New York, 11201, United States

Location

University at Buffalo

Buffalo, New York, 14203, United States

Location

AXIS Clinical Trials

New York, New York, 10022, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10025, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Research Inc.

Raleigh, North Carolina, 27612, United States

Location

Synexus Clinical Research US, Inc. - Akron

Akron, Ohio, 44311, United States

Location

Synexus Clinical Research US, Inc. - Cincinnati

Cincinnati, Ohio, 45236, United States

Location

Synexus Clinical Research US, Inc. - Columbus

Columbus, Ohio, 43016, United States

Location

Obesity Institute, Geisinger Clinic

Danville, Pennsylvania, 17822, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

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

Anderson, South Carolina, 29621, United States

Location

Wake Research TN

Chattanooga, Tennessee, 37421, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37212-3157, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Synexus Clinical Research US, Inc. - Plano

Plano, Texas, 75093, United States

Location

Synexus Clinical Research US, Inc. - San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

Marshfield Clinic Research Institute

Marshfield, Wisconsin, 54449, United States

Location

University of Alberta

Edmonton, T6G 2E1, Canada

Location

Hopital Trousseau - Nutrition et Gastroentérologie

Paris, 75012, France

Location

Hopital de la Pitié-Salpêtrière

Paris, 75013, France

Location

Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon

Saint-Denis, 97405, France

Location

Charité Berlin

Berlin, 13354, Germany

Location

University of Leipzig

Leipzig, 04103, Germany

Location

University of Ulm

Ulm, 89075, Germany

Location

University General Hospital of Patras

Rio, Patras, 26504, Greece

Location

Edmond and Lily Safra Children's Hospital

Ramat Gan, 52621, Israel

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

Hospital Infantil Universitario Niño Jesús

Madrid, 65 28009, Spain

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

Related Publications (2)

  • Ervin C, Norcross L, Mallya UG, Fehnel S, Mittleman RS, Webster M, Haqq AM, Haws RM. Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome. Adv Ther. 2023 May;40(5):2394-2411. doi: 10.1007/s12325-023-02443-y. Epub 2023 Mar 24.

  • 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.

MeSH Terms

Conditions

ObesitySmith-Magenis Syndrome

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsChronobiology DisordersNervous System DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesChromosome DisordersGenetic Diseases, Inborn

Results Point of Contact

Title
Rhythm Clinical Trials
Organization
Rhythm Pharmaceuticals, Inc.

Study Officials

  • David Meeker, MD

    Rhythm Pharmaceuticals, Inc.

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 3, 2017

First Posted

January 6, 2017

Study Start

February 10, 2017

Primary Completion

March 1, 2022

Study Completion

March 1, 2022

Last Updated

August 18, 2023

Results First Posted

August 18, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations