A clinical trial to study the efficacy and safety of an investigational medication, beloranib, in treatment of food-related behaviour and weight in obese individuals with Prader-Willi Syndrome by comparison with placebo

Phase 1

Conditions: Improvement of Hyperphagia and related behaviors as well as Body Composition/Overweight in Prader-Willi-Syndrome
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
MedDRA version: 18.1 Level: PT Classification code 10036476 Term: Prader-Willi syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Registration Number: EUCTR2015-000660-33-FR

Lead Sponsor: Zafgen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 150

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 <10%).
6) If a subject has current diagnosis of T2DM, the following criteria must be met:
a. HbA1c <10.0%
b. Fasting glucose <240 mg/dL (<13.3 mmol/L)
c. No history of ketoacidosis or hyperosmolar coma
7) All study participants must agree to use an approved method of contraception throughout the study (unless subject is confirmed to be infertile or has a history of and/or commitment of long-term abstinence).
Females
a. Intra-uterine device (IUD) in place from Screening through study completion as deemed appropriate for patient use by the treating physician's judgement.
b. Stable hormonal contraception (with approved oral, transdermal, or depot regimen) for at least 3 months prior to Screening through study completion
Male partners of female subjects must use a barrier method (e.g. condom) in addition to the female subject having an IUD in place or using stable hormonal contraception.
Males that are sexually active
c. Barrier method (e.g., condom) from Screening through study completion
AND one of the following:
d. Female partner has IUD in place from Screening or stable hormonal contraception for at least 3 months prior to Screening through study completion
OR
e. Female partner is infertile
(Infertility for females is defined as surgically sterile or those who have had 12 months of amenorrhea and negative urine pregnancy test at Screening.)
8) Subjects must be able to provide or have a guardian who is able to provide written informed consent.
9) Subject must be current on immunizations prior to enrollment, as prescribed by their health care professional according to the investigative site’s standard of care.
10) Subjects must have at least one consistent and reliable primary caregiver who is able to accurately evaluate changes in the subject’s mood, AEs, behavior, and document MRU (e.g., planned and unplanned visits to healthcare providers, emergency room visits, hospitalization, etc.) throughout the study. The caregiver must have been caring for the subject for at least 6 months prior to study entry, is anticipated to be the subject’s primary caregiver for the duration of the trial, and spends at least 4 waking hours per day on average with the subject. The caregiver must be able to read and understand the local language or be able to communicate with Investigator/site staff.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes

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 (<60 mL/min).
4) Type 1 diabetes mellitus or current or recent use of insulin (more than 1 week within 3 months prior to Screening).
5) Uncontrolled endocrine disorders (e.g., Cushing syndrome, Addison’s, hypothyroidism, hypogonadism), except T2DM with HbA1c<10%.
6) Clinically significant and abnormal Screening hematology lab results or recurring infections, or if any of the following are observed (regardless of the Investigator’s assessment of clinical significance):
a. Hemoglobin <10 g/dL (<100 g/L)
b. Absolute neutrophil count (ANC) <2000/mm^3
c. Platelets <135 x 10^9/L
7) Results of Screening clinical laboratory tests (complete blood count [CBC] with differential and platelets, chemistry, and urinalysis profile) and ECG outside normal range and considered to be clinically significant by the Investigator.
8) Subjects on the following systemic concomitant medications who have not been on stable dose (or stable weight based dose), defined as no more than ±25% variation in dose, for at least 3 months prior to study entry:
a. Growth hormone
b. Glucocorticoids
c. Vasopressin
d. Thyroid hormone
e. Testosterone
f. Other hormone or hormone replacement therapies
g. Anti-obesity agents (must have been stable for =6 months)
h. Anti-diabetes medications (except for glucagon-like peptide-1 [GLP-1] analogues or sodium-glucose linked transporter 2 (SGLT2) inhibitors must have been stable for =6 months)
i. Modafinil
j. Atypical anti-psychotics
k. Anti-depressive
l. Attention deficit hyperactivity disorder (ADHD) medications

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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