Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity

Obesity Clinical Trial

Official title:

Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03013543
• Other study ID #: RM-493-014
• Secondary ID: 2017-000387-14
• Status: Completed
• Phase: Phase 2
• Start date: February 10, 2017
• Est. completion date: March 1, 2022

Study information

• Verified date: July 2023
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Genetic Diseases, Inborn
• Obesity

Intervention

Drug:
• Setmelanotide
RM-493 QD SC injection

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton
France	Hopital de la Pitié-Salpêtrière	Paris
France	Hopital Trousseau - Nutrition et Gastroentérologie	Paris
France	Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon	Saint-Denis
Germany	Charité Berlin	Berlin
Germany	University of Leipzig	Leipzig
Germany	University of Ulm	Ulm
Greece	University General Hospital of Patras	Río	Patras
Israel	Edmond and Lily Safra Children's Hospital	Ramat Gan
Netherlands	Erasmus MC	Rotterdam
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Hammersmith Hospital	London
United Kingdom	Hammersmith Hospital	London
United States	Synexus Clinical Research US, Inc. - Akron	Akron	Ohio
United States	Synexus Clinical Research US, Inc. - Primary Care Associates, PC	Anderson	South Carolina
United States	University of Michigan Medicine	Ann Arbor	Michigan
United States	Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	NIH Hatfield Clinical Research Center	Bethesda	Maryland
United States	Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC	Birmingham	Alabama
United States	AXIS New York Clinical Trials	Brooklyn	New York
United States	University at Buffalo	Buffalo	New York
United States	Synexus Clinical Research US, Inc. - Phoenix Southeast	Chandler	Arizona
United States	Wake Research TN	Chattanooga	Tennessee
United States	Synexus Clinical Research US, Inc. - Chicago	Chicago	Illinois
United States	Synexus Clinical Research US, Inc. - Cincinnati	Cincinnati	Ohio
United States	Synexus Clinical Research US, Inc. - Columbus	Columbus	Ohio
United States	Obesity Institute, Geisinger Clinic	Danville	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida College of Medicine	Gainesville	Florida
United States	AXIS South Florida Clinical Trials	Hialeah	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Impact Clinical Trials	Las Vegas	Nevada
United States	Axis Clinical Trials Headquarters	Los Angeles	California
United States	Axis Clinical Trials-Downtown	Los Angeles	California
United States	Marshfield Clinic Research Institute	Marshfield	Wisconsin
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC	Mesa	Arizona
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	AXIS Clinical Trials	New York	New York
United States	Columbia University	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Florida Hospital	Orlando	Florida
United States	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Synexus Clinical Research US, Inc. - St. Petersburg	Pinellas Park	Florida
United States	Synexus Clinical Research US, Inc. - Plano	Plano	Texas
United States	Maine Medical Partners	Portland	Maine
United States	Wake Research Inc.	Raleigh	North Carolina
United States	Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic	Rochester	Minnesota
United States	Washington University St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Synexus Clinical Research US, Inc. - San Antonio	San Antonio	Texas
United States	San Diego Wake Research	San Diego	California
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Seattle Children's Research Institute	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Division of Endocrinology and Diabetes Children's National Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Greece,  Israel,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With = 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment		Baseline to Month 3
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAEs were defined as AEs reported after dosing on Day 1.	From first dose up to Month 16
Secondary	Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment		Baseline, Month 3
Secondary	Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment		Baseline, Month 3
Secondary	Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged = 12 Years	The mean change in daily hunger questionnaire scores for participants = 12 years of age with obesity in treatment with setmelanotide was evaluated. On the Daily Hunger Questionnaire, each of the 3 items (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) was assessed daily and scored separately using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible.	Baseline, Month 3
Secondary	Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years	The mean change in daily hunger questionnaire scores for participants < 12 years of age with obesity in treatment with setmelanotide was evaluated. Hunger was assessed daily using a Daily Hunger Questionnaire with a pictorial (smiley face) version of the Likert rating scale with scores ranged from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible.	Baseline, Month 3
Secondary	Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged = 12 Years	For participants = 12 years of age, the following question was asked using the Global Hunger Questionnaire: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; Severe hunger; and Not answered.	Baseline, Month 3
Secondary	Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years	For participants < 12 years of age, the following question was asked to parents or caregivers of participants using the Global Hunger Questionnaire: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; Extremely hungry; and Not answered.	Baseline, Month 3
Secondary	Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment	Waist circumference (cm) was measured according to the National Heart, Lung, and Blood Institute (NHLBI) criteria. All measurements were single measures. Waist circumference was measured when participants were in fasting condition and at approximately the same time at each visit.	Baseline, Month 3