Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome

NCT02311673 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: RM-493-010R01FD005094-01A1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study was to evaluate the effects of a once daily subcutaneous injectable formulation of setmelanotide in obese participants with Prader-Willi syndrome on tolerability, weight loss, and hyperphagia-related behavior. The study drug (setmelanotide and placebo) was administered in a blinded fashion.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi Syndrome; obesity; hyperphagia

Outcome Measures

Primary Outcomes (7)

• Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2

  An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect

  Days 15 to 41

• Number of Participants Who Experienced a TEAE - Period 3

  An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect

  Days 42 to 55

• Number of Participants Who Experienced a TEAE - Period 4

  An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect

  Days 56 to 69

• Mean Body Weight - Period 2

  Baseline (Day 15)

• Percent Change From Baseline in Body Weight - Period 2

  Baseline (Day 15) and Day 42

• Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2

  The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia).

  Baseline (Day 15)

• Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2

  The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented.

  Baseline (Day 15) and Day 42

Secondary Outcomes (19)

• Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2

  Baseline (Day 15) and Day 42

• Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2

  Baseline (Day 15) and Day 42

• Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2

  Baseline (Day 15) and Day 42

• Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3

  Baseline (Day 42) and Day 56

• Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4

  Baseline (Day 56) and Day 70

Study Arms (4)

Setmelanotide 0.5 mg

EXPERIMENTAL

Participants received setmelanotide 0.5 milligrams (mg) once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period) and Day 42 to Day 55 (2-week, randomized withdrawal period).

Drug: Setmelanotide

Setmelanotide 1.5 mg

EXPERIMENTAL

Participants received setmelanotide 1.5 once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period), Day 42 to Day 55 (2-week, randomized withdrawal period), and Day 56 to Day 69 (optional 2-week, open-label extension period).

Drug: Setmelanotide

Setmelanotide 2.5 mg

EXPERIMENTAL

Participants received setmelanotide 2.5 once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period), Day 42 to Day 55 (2-week, randomized withdrawal period), and Day 56 to Day 69 (optional 2-week, open-label extension period).

Drug: Setmelanotide

Placebo

PLACEBO COMPARATOR

Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind run-in period), Day 15 to Day 41 (4-week, double-blind randomized treatment period), and Day 42 to Day 55 (2-week, randomized withdrawal period).

Drug: Placebo

Interventions

Setmelanotide DRUG

subcutaneous injection

Also known as: RM-493

Setmelanotide 0.5 mg; Setmelanotide 1.5 mg; Setmelanotide 2.5 mg

Placebo DRUG

Subcutaneous injection

Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PWS due to chromosome 15 micro-deletion, maternal uniparental disomy, or imprinting defect, confirmed by fluorescent in situ hybridization, chromosomal microarray, and/or methylation studies. Obese male or female participants weighing at least 50 kilograms (kg) with body mass index (BMI) ≥ 27 kilogram per square meter (kg/m²)
• Age 16-65 years
• If a participant has diagnosis of type 2 diabetes, following criteria must be met:
• hemoglobin A1C (HbA1c) \< 7.5% not being managed with insulin. Participants taking glucagon-like peptide-1 (GLP-1) analogues (exenatide or liraglutide) must have been on stable dose for greater than 3 months.
• Fasting plasma glucose \< 140 milligrams per deciliter (mg/dL)
• No history of ketoacidosis or hyperosmolar coma
• Vital signs must be within the following ranges and stable.
• Systolic blood pressure, 90-150 millimeter of mercury (mm Hg)
• Diastolic blood pressure, 50-90 mm Hg
• Pulse rate, 40-100 beats per minute (bpm)
• Stable body weight at home for approximately 2 months (self or guardian-reported loss/gain within ± 5%).
• Blood pressure (≤ 150/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications that are intended to remain on a stable dose during the protocol
• Parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent. Due to the significant intellectual disability with PWS, assent is to be provided by the participant who cannot consent for himself or herself.
• Results of screening clinical laboratory tests (complete blood count with differential and platelets and chemistry profile) must be within normal range or, if outside of the normal range, must be accepted by the investigator and sponsor as not clinically significant.
• Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months (and confirmed with a screening follicle-stimulating hormone (FSH) level in the post-menopausal lab range), do not require contraception during the study. All other females of child-bearing potential must agree to use contraception as outlined in the protocol.

You may not qualify if:

• Recent use (within 3 month) of weight loss agents including herbal medication.
• Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) disorders which the investigator believes will interfere significantly with study compliance.
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
• Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Clinically significant illness in the 8 weeks before screening.
• History of clinically significant bleeding disorders.
• Current, clinically significant liver, renal, pulmonary, cardiac, oncologic, or gastrointestinal disease.
• Diagnosis of type 1 diabetes mellitus or other active endocrine disorders (e.g., Cushing syndrome, or thyroid dysfunction except if on adequate thyroid or glucocorticoid replacement supplement).
• Cardiovascular disease event including history of congestive heart failure, coronary artery disease, myocardial infarction, second degree or greater heart block or prolonged QT syndrome.
• Blood pressure \> 150/90 mm Hg.
• Liver disease or liver injury as indicated by abnormal liver function tests, aspartate aminotransferase, alkaline phosphatase, or serum bilirubin (\> 1.5 x upper limit of normal for any of these tests) or history of hepatic cirrhosis.
• History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine, blood urea nitrogen, or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by the Cockcroft-Gault equation (\< 50 mL/min).
• History or close family history (parents or siblings) of melanoma.
• Oculocutaneous albinism (occurs at approximately 1% in PWS).
• Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist.

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (5)

University of California Irvine

Irvine, California, 92617, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Vanderbilt University

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Prader-Willi Syndrome; Obesity; Hyperphagia

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Results Point of Contact

• Title: Rhythm Clinical Trials
• Organization: Rhythm Pharmaceuticals, Inc.

clinicaltrials@rhythmtx.com

857-264-4280

Study Officials

• David Meeker

  Rhythm Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: December 8, 2014
• Study Start: March 19, 2015
• Primary Completion: October 26, 2016
• Study Completion: October 26, 2016
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)