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Ph 2 Trial to Evaluate Safety & Efficacy of RM-493 in Obese Patients With Prader-Willi Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02311673
First received: November 25, 2014
Last updated: April 19, 2017
Last verified: April 2017
  Purpose

The purpose of this study is to evaluate the effects of a once daily subcutaneous (SC) injectable formulation of RM-493 in obese subjects with Prader-Willi syndrome on tolerability, weight loss and hyperphagia-related behavior. The study drug (RM-493 and placebo) will be administered in a blinded fashion.

Funding Source - FDA OOPD


Condition Intervention Phase
Prader-Willi Syndrome Drug: RM-493 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Ph 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

Resource links provided by NLM:


Further study details as provided by Rhythm Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Assess safety and tolerability of RM-493 (adverse events and clinical laboratory evaluations) [ Time Frame: Baseline to Day 70 or until any adverse events are resolved ]
    Assessment of adverse events and clinical laboratory evaluations.

  • Effect on weight loss [ Time Frame: Baseline to Day 56 ]
    Measurement of the effect of RM-493 on weight loss.

  • Effect on hyperphagia-related behavior (using the PWS Hyperphagia Questionnaire) [ Time Frame: Baseline to Day 56 ]
    Measurement of the effect of RM-493 on hyperphagia-related behavior using the PWS Hyperphagia Questionnaire.


Secondary Outcome Measures:
  • Effect on quality of life. [ Time Frame: Baseline to Day 56 ]
    Measurement of the effect of RM-493 on quality of life as measured by thee Food Related Problem Questionnaire and/or the Hospital Anxiety and Depression Questionnaire

  • Effect on food-related behavior. (daily journal and/or Rate of Eating Questionnaire) [ Time Frame: Baseline to Day 56 ]
    Measurement of the effect of RM-493 on food-related behavior. A daily journal will be used to quantify aberrant behavior and/or a Rate of Eating Questionnaire will be used

  • Effect on psychiatric status. (C-SSRS and PHQ-9 Questionnaires) [ Time Frame: Baseline to Day 70 ]
    Measurement of the effect of RM-493 on psychiatric status as assessed using the C-SSRS and PHQ-9 Questionnaires.

  • Effect of on Pharmacokinetics (PK) (Frequent PK (trough) sampling) [ Time Frame: Baseline to Day 70 ]
    Frequent PK (trough) sampling throughout each stage of the study, including a 12-hour PK profile.

  • Effect of dose adjustment of RM-493 [ Time Frame: Baseline to Day 56 ]
    Measurement of the effect of dose adjustment of RM-493 as assessed by measuring weight fluctuations from Baseline to Day 56.


Enrollment: 40
Study Start Date: February 2015
Study Completion Date: December 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RM-493 Once Daily Dose 1
Dose 1 once daily in the morning
Drug: RM-493
subcutaneous injection
Other Name: setmelanotide
Active Comparator: RM-493 Once Daily Dose 2
Dose 2 once daily in the morning
Drug: RM-493
subcutaneous injection
Other Name: setmelanotide
Placebo Comparator: Placebo
Placebo in the morning
Drug: Placebo
subcutaneous injection

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 volunteers weighing at least 50 kg with BMI ≥27 kg/m²
  2. Age 16-65 years
  3. If a volunteer has diagnosis of type 2 diabetes, following criteria must be met:

    1. HbA1c <7.5% not being managed with insulin. Patients taking GLP-1 analogues (exenatide or liraglutide) must have been on stable dose for greater than 3 months.
    2. Fasting plasma glucose <140 mg/dL
    3. No history of ketoacidosis or hyperosmolar coma
  4. Vital signs must be within the following ranges and stable.

    1. Systolic blood pressure, 90-150 mm Hg
    2. Diastolic blood pressure, 50-90 mm Hg
    3. Pulse rate, 40-100 bpm
  5. Stable body weight at home for ~2 months (self or guardian-reported loss/gain within ± 5%).
  6. 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
  7. 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 patient who cannot consent for himself or herself.
  8. Results of screening clinical laboratory tests (CBC 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.
  9. 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 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.
  10. 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 subjects must not donate sperm for 90 days following their participation in the study.
  11. Patients must be on a stable dose of any allowed chronic concomitant medications while participating in the study, as described in protocol. This is defined as no changes in medication for at least 60 days prior to Day 1 and no changes in dose for at least 30 days prior to Day 1; Note that stable concomitant usage (>3 months) of growth hormone, hormone replacement therapy, GLP-1 agents, statins, or other medications (excluding insulin, modafinil, anti-psychotics), and other medications commonly used in PWS patients are allowed (See Section 6.4.5 on Concomitant medications).

Exclusion Criteria:

  1. Recent use (within 3 month) of weight loss agents including herbal medication.
  2. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other DSM-III disorders which the investigator believes will interfere significantly with study compliance.
  3. A PHQ-9 score of ≥15.
  4. Any suicidal ideation of type 4 or 5 on the C-SSRS.
  5. Clinically significant illness in the 8 weeks before screening.
  6. History of clinically significant bleeding disorders.
  7. Current, clinically significant liver, renal, pulmonary, cardiac, oncologic, or GI disease.
  8. 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).
  9. Cardiovascular disease event including history of CHF, coronary artery disease, MI, second degree or greater heart block or prolonged QT syndrome.
  10. Blood pressure >150/90 mmHG.
  11. Liver disease or liver injury as indicated by abnormal liver function tests, SGOT (AST), alkaline phosphatase, or serum bilirubin (> 1.5 x ULN for any of these tests) or history of hepatic cirrhosis.
  12. History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine, BUN, or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by the Cockroft Gault equation (< 50 mL/min).
  13. History or close family history (parents or siblings) of melanoma.
  14. Oculocutaneous albinism (occurs at ~1% in PWS).
  15. Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist. Any concerning lesions identified during the screening period will be biopsied and results known to be benign prior to randomization. If the pre-treatment biopsy results are of concern, the patient will be excluded from the study.
  16. Significant history of abuse of drugs or solvents in the year before screening or a positive Drugs of Abuse (DOA) test at screening.
  17. 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).
  18. Caffeine consumption exceeding 6 cups of caffeinated tea/coffee (or equivalent) per day.
  19. Volunteer is, in the opinion of the Investigator, not suitable to participate in the study.
  20. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  21. Positive history for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C tests or tuberculosis.
  22. Serious adverse reaction or significant hypersensitivity to any drug.
  23. Clinically significant blood loss or blood donation > 500 mL within 3 month.
  24. Inadequate venous access.
  25. History of low blood counts or recurring infections.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02311673

Locations
United States, California
University of California Irvine
Irvine, California, United States, 92617
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
Study Director: Fred Fiedorek, MD Rhythm Pharmaceuticals, Inc.
  More Information

Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02311673     History of Changes
Other Study ID Numbers: RM-493-010
R01FD005094-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: November 25, 2014
Last Updated: April 19, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhythm Pharmaceuticals, Inc.:
Prader-Willi Syndrome
obesity
hyperphagia

Additional relevant MeSH terms:
Syndrome
Prader-Willi Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders

ClinicalTrials.gov processed this record on June 23, 2017