Improvement of Hyperphagia and related behaviors as well as Body Composition/Overweight in Prader-Willi-Syndrome MedDRA version: 18.0 Level: PT Classification code 10036476 Term: Prader-Willi syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Subcutaneous Beloranib in Suspension
Product Code: ZGN-440
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: Beloranib
CAS Number: 251111-30-5
Cur
Sponsors
Zafgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age 12-50 years, inclusive. 2) Confirmed diagnosis of PWS due to chromosome 15 micro-deletion, maternal uniparental disomy, or imprinting defect. Documentation of PWS, including variant of genetic defect in the subject’s medical record is sufficient. 3) HQ-CT score =11 (scale of 0-36). 4) Obese a. Age 12-17 years: Body mass index (BMI) =90th percentile for age and gender (per United Kingdom [UK] Royal College of Pædiatrics and Child Health BMI charts) b. Age 18-50 years: BMI =27 to =70 kg/m^2 5) Stable body weight for 3 months (self or guardian-reported loss/gain =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Poorly controlled severe psychiatric disorders (e.g., schizophrenia, bipolar disorder, or major depressive order), recent (within 6 months) psychotic episodes, history of suicide attempts or suicidal ideation, or any other psychiatric disorders that the Investigator believes will interfere significantly with study compliance. 2) History of any bleeding disorders, deep vein thrombosis (DVT), or thromboembolic disease. 3) Current liver, renal, pulmonary, cardiac, oncologic, or GI disease which the Investigator believes is clinically significant, including: a. Significant cardiovascular disease including history of congestive heart failure (CHF), coronary artery disease, myocardial infarction (MI), second degree or greater heart block , prolonged time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole (QT) syndrome, or clinically significant arrhythmias. b. Fridericia-corrected QT interval (QTcF) >460 msec for males and QTcF >480 msec for females pre-dose on Day 1. c. Liver disease or liver function tests, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3x upper limit of normal (ULN), alkaline phosphatase (ALP) or serum bilirubin >3x ULN, or history of hepatic cirrhosis. d. History or presence of impaired renal function as indicated by clinically significant abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents or moderate to severe renal dysfunction as defined by the Cockcroft-Gault equation (160 mm Hg b. Diastolic blood pressure >100 mm Hg c. Pulse rate >100 beats per minute (bpm) 10) Recent (within the last year) and/or recurrent history of autonomic dysfunction (e.g., unexplained syncope or palpitations). 11) Current or anticipated chronic use (more than 2 days) of narcotics or opiates. 12) Significant history of abuse of drugs or sol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess changes in hyperphagia-related behaviors and total body weight for beloranib administered over 52 weeks - To assess safety and tolerability effects of beloranib administered over 52 weeks;Secondary Objective: - To assess changes in total body fat mass as measured by DXA for beloranib over 52 weeks (sub-study, not to be pursued at investigational sites in Germany);Timepoint(s) of evaluation of this end point: - Hyperphagia-related behavior checklist should be completed by the caregiver for at least 7 days prior to arriving at the site at the following visits: Day 1, Week 4, 12, 26, 42 ,52 and Early Termination. - Weight to be assessed at: Day 1, Week 4, 8, 12, 18, 26, 34, 42, 52 and Early Termination;Primary end point(s): The co-primary efficacy endpoints are: - Change from baseline to the end of the double-blind 52-week randomized treatment for hyperphagia-related behavior (HQ-CT total score) - Percent change from baseline to the end of the double-blind 52-week randomized treatment in total body weight For each of these two endpoints, baseline is defined as the measurement obtained at the most recent assessment on or prior to the date of first randomized dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints are: 1. % HQ-CT responders at the end of the double-blind 52-week randomized treatment 2. Change in total body fat mass per DXA from baseline to the end of the double-blind 52-week ramdomized treatment (sub-study) 3. Change in Low-density lipoprotein (LDL) cholesterol from baseline to the end of the double-blind 52-week randomized treatment 4. Change in high-density lipoprotein (HDL) cholesterol from baseline to the end of the double-blind 52-week randomized treatment Additional secondary endpoints, each of which is defined as the change from baseline to the end of the double-blind 52-week randomized treatment, are: 1. Total body mass per DXA (sub-study) 2. Number of active skin lesions 3. High-sensitivity C-reactive protein (hs-CRP) 4. Triglyceride 5. Total cholesterol 6. Total lean body mass per DXA (sub-study);Timepoint(s) of evaluation of this end point: - (sub-study) Total body fat mass, total body mass, total lean body mass, all per DXA : Week 26, 52, Early Termination -% HQ-CT responders: Week 4, 12, 26, 42, 52, Early Termination - Total cholesterol, Triglyceride, Low-density lipoprotein (LDL) cholesterol, High-density lipoprotein (HDL), High-sensitivity C-reactive protein (hs-CRP)cholesterol, Number of active skin lesions: Day 1, Week 4, 12, 26, 42, 52, Early Termination | — |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Science Department
Zafgen Inc.
Outcome results
None listed