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Prader-Willi SyndromePhase 2NCT02311673

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

A Phase 2 study testing Setmelanotide in people with Prader-Willi Syndrome, run by Rhythm Pharmaceuticals, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 65 years
Conditions the study is for
Prader-Willi Syndrome
What is being tested?
Setmelanotide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
5 sitesUnited States
Study dates
19 Mar 2015to 26 Oct 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Males with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study and for 90 days following the study. Male participants must not donate sperm for 90 days following their participation in the study.
  • Participants must be on a stable dose of any allowed chronic concomitant medications while participating in the study.

Who cannot join

  • 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.
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  • 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.
  • Significant history of abuse of drugs or solvents in the year before screening or a positive Drugs of Abuse (DOA) test at screening.
  • History of alcohol abuse in the past year before screening or currently drinks in excess of 21 units per week (3 servings or units/day).
  • Caffeine consumption exceeding 6 cups of caffeinated tea/coffee (or equivalent) per day.
  • Participant is, in the opinion of the Investigator, not suitable to participate in the study.
  • Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  • Positive history for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C tests or tuberculosis.
  • Serious adverse reaction or significant hypersensitivity to any drug.
  • Clinically significant blood loss or blood donation > 500 milliliters (mL) within 3 months.
  • Inadequate venous access.
  • History of low blood counts or recurring infections.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Florida

    Gainesville, Florida, 32610

  • University of California Irvine

    Irvine, California, 92617

  • Kansas University Medical Center

    Kansas City, Kansas, 66160

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Vanderbilt University

    Nashville, Tennessee, 37203

Other trials in United States

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-controlled Pilot Study to Assess the Effects of RM-493, a Melanocortin 4 Receptor (MC4R) Agonist, in Obese Subjects With Prader-Willi Syndrome (PWS) on Safety, Weight Reduction, and Food-Related Behaviors

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.

Being tested
Setmelanotide, Placebo
Keywords
Prader-Willi Syndrome, obesity, hyperphagia
Medical subject headings
Prader-Willi Syndrome, Obesity, Hyperphagia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SetmelanotideDrug

    Also called RM-493

    subcutaneous injection

  • PlaceboDrug

    Subcutaneous injection

Study groups in NCT02311673
Study groupRoleWhat they receive
Setmelanotide 0.5 mgExperimentalParticipants 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).
Receives: Drug: Setmelanotide
Setmelanotide 1.5 mgExperimentalParticipants 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).
Receives: Drug: Setmelanotide
Setmelanotide 2.5 mgExperimentalParticipants 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).
Receives: Drug: Setmelanotide
PlaceboPlacebo comparatorParticipants 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Days 15 to 41

  2. 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

    Measured: Days 42 to 55

  3. 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

    Measured: Days 56 to 69

  4. Mean Body Weight - Period 2

    Measured: Baseline (Day 15)

  5. Percent Change From Baseline in Body Weight - Period 2

    Measured: Baseline (Day 15) and Day 42

  6. 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).

    Measured: Baseline (Day 15)

  7. 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.

    Measured: Baseline (Day 15) and Day 42

Secondary outcomes (19)

  1. Percent Change From Baseline in Hyperphagic Drive Score of 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. Hyperphagic drive score assesses the persistence in asking for food based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic drive range from a minimum score of 4 (no hyperphagic drive) to a maximum score of 20 (greater hyperphagic drive). Percent change from baseline in hyperphagic drive score of PWS hyperphagia questionnaire is presented.

    Measured: Baseline (Day 15) and Day 42

  2. Percent Change From Baseline in Hyperphagic Behaviors Score of 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. Hyperphagic behavior factor score assesses food seeking behaviors based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic behaviors range from a minimum score of 4 (no hyperphagic behavior) to a maximum score of 20 (greater hyperphagic behavior). Percent change from baseline in hyperphagic behaviors score of PWS hyperphagia questionnaire is presented.

    Measured: Baseline (Day 15) and Day 42

  3. Percent Change From Baseline in Hyperphagic Severity Score of 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. Hyperphagic severity factor score assesses the severity of hyperphagia based on 2 items. Both items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic severity range from a minimum score of 2 (no hyperphagic severity) to a maximum score of 10 (greater hyperphagic severity). Percent change from baseline in hyperphagic severity score of PWS hyperphagia questionnaire is presented.

    Measured: Baseline (Day 15) and Day 42

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

    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.

    Measured: Baseline (Day 42) and Day 56

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

    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.

    Measured: Baseline (Day 56) and Day 70

  6. Mean Setmelanotide Trough Concentrations

    The average of setmelanotide trough concentrations values for both timepoints (5 minutes predose on Day 42 and Day 70) is presented.

    Measured: 5 minutes predose on Day 42 and Day 70

  7. Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval

    Maximum drug concentration determined directly from individual concentration-time data.

    Measured: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing

  8. Time to the Maximum Drug Concentration (Tmax) of Setmelanotide During a 24-Hour Steady-State Interval

    Maximum drug concentration determined directly from individual concentration-time data.

    Measured: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing

  9. Area Under the Drug Concentration-Time Curve From Time-Zero to 24 Hours Postdose (AUC24h) of Setmelanotide During a 24-Hour Steady-State Interval

    Measured: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing

  10. Volume of Distribution (Vd) of Setmelanotide During a 24-Hour Steady-State Interval

    Volume of distribution calculated as Dose/The observed terminal rate constant*AUC24h.

    Measured: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing

  11. Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval

    Clearance after extravascular administration; calculated as Dose/AUC24h.

    Measured: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing

  12. Change From Baseline in Body Weight - Period 2

    Measured: Baseline (Day 15) and Day 42

  13. Percent Change From Baseline in Body Weight - Period 3

    Measured: Baseline (Day 42) and Day 56

  14. Percent Change From Baseline in Body Weight - Period 4

    Measured: Baseline (Day 56) and Day 70

  15. Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3

    Measured: Baseline (Day 15), Day 42, Day 56

  16. Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2

    Total body fat was assessed by DEXA scan.

    Measured: Baseline (Day 15) and Day 42

  17. Number of Participants With Clinically Significant Percent Change From Baseline in Body Fat Measured Using DEXA - Period 4

    Total body fat was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body fat were judged by investigator.

    Measured: Baseline (Day 56) and Day 70

  18. Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2

    Total body mass was assessed by DEXA scan.

    Measured: Baseline (Day 15) and Day 42

  19. Number of Participants With Clinically Significant Percent Change From Baseline in Body Mass Measured Using DEXA - Period 4

    Total body mass was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body mass were judged by investigator.

    Measured: Baseline (Day 56) and Day 70

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2014 (estimated)
  2. Study start19 Mar 2015
  3. Primary completion26 Oct 2016
  4. Study completion26 Oct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02311673
Sponsor's protocol ID
RM-493-010
Other IDs
R01FD005094-01A1
Status last verified
Jul 2023
First submitted
25 Nov 2014
Last updated
27 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Setmelanotide in people with Prader-Willi Syndrome, run by Rhythm Pharmaceuticals, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 (time frame: Days 15 to 41). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02311673.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

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