This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety, tolerability, and effects of livoletide on food-related behaviors in patients with Prader-Willi Syndrome (PWS).
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Appetite and general nutritional disorders
- Eating disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Outcome Measures :
Change in hyperphagia and food-related behaviors (Hyperphagia Questionnaire for
Clinical Trials; HQ-CT) [ Time Frame: Baseline to month 3 ]
Change from baseline to the end of the 3-month Core Period for HQ-CT total
score. The HQ-CT score range is 0 to 36 where the higher score represents more
severe abnormal food related behaviors.
Secondary outcome
Secondary Outcome Measures :
Change in fat mass [ Time Frame: Baseline to month 3 ]
Percentage change from baseline to the end of the 3-month Core Period in total
body fat mass in overweight/obese patients with PWS
Change in waist circumference [ Time Frame: Baseline to month 3 ]
Change from baseline to the end of the 3-month Core Period in waist
circumference in overweight/obese patients with PWS
Change in body weight [ Time Frame: Baseline to month 3 ]
Percentage change from baseline to the end of the 3-month Core Period in body
weight in overweight/obese patients with PWS
Background summary
Prader-Willi syndrome (PWS) is genetic disorder, which is caused by the absence
of some genes on chromosome 15. Genes are contributing to making you different
this is why there so many different people with different hair and eye colours.
Because of the absence of these genes in PWS, PWS patients will develop several
disease specific features including short stature (growth hormone deficiency),
dysmorphic features, hypogonadism, low calorie expenditure, and abnormal body
composition with reduced fat free mass and increased fat mass. Patients with
PWS also suffer from cognitive impairments, behavioural disturbances, and
psychiatric disorders. These patients also suffer from hyperphagia (this is a
feeling of insatiable hunger) and food-related behaviours, which is the worst
salient and constant symptom of PWS. Hyperphagia leads to significant mortality
and morbidity. Currently, there no approved prescription or over-the counter
drugs for the treatment of hyperphagia and food-related behaviours in patients
with PWS.
This study involves research and is being conducted to test if a drug called
livoletide will have an effect on hyperphagia and food-related behaviors. The
study will also test if livoletide is safe and well tolerated. Livoletide is an
investigational drug. This means that livoletide is still being studied.
Livoletide (AZP-531) is a synthetic molecule (chain of 8 amino acids), similar
to physiological hormone unacylated Ghrelin. Livoletide might counteract the
effect of another hormone in the body called Ghrelin (AG). Ghrelin (AG)
stimulates appetite and has obesogenic and diabetiogenic properties
Study objective
This Phase 2b/3 double-blind, placebo-controlled study will evaluate the
safety, tolerability, and effects of livoletide on food-related behaviors in
patients with Prader-Willi Syndrome (PWS).
Study design
This is a double-blind, randomized, multi center placebo-controlled study with
livoletide in patients with Prader-Willi Syndrome.
Intervention
Experimental: Low-Dose Livoletide
Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core
period and 9 month open label extension period.
Experimental: High-Dose Livoletide
Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core
period and 9 month open label extension period.
Placebo Comparator: Placebo
Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core
period and then low-dose or high-dose livoletide for 9 month open label
extension period.
Study burden and risks
Participation in this study will include approximately 14 Months. During this
study the following study procedures will be performed:
Questions about health and medications, physical exam (including vital signs,
height and weight, WC, BW and BMI), ECG, DXA-scan, pregnancy test, different
blood tests, consumption of isocaloric breakfast, completing different
questionnaires (Appetite-NRS, HQ-CT, Quality of Life: PedsQL* Parent-Proxy
Report, Caregiver and Clinical Global Impression of Severity - Hyperphagia
scales (CgGIS-H and CGIS-H), Caregiver and Clinical Global Impression of
Change - Hyperphagia scales (CgGIC-H and CGIC-H), Clinical Global Impression of
Improvement (CGI-I), Clinical Global Impression
of - Severity (CGI-S) scale; EQ-5D-5L, and Developmental Behavior Checklist
2-Parent/Carer (DBC2-P).
When taking blood samples the subject may feel pain or be light-headed. The
subject may have the following reactions at the site of the needle stick when
blood is drawn:
- Additional bleeding at the site of the blood draw
- Temporary discomfort
- Bruising
- Infection (rarely)
During the electrocardiogram, subjects may experience temporary discomfort
(pulling on the skin/skin hair) during removal of the sensors. They may develop
some minor skin irritation from the ECG patch adhesive.
Subject are asked to fast for 8 hours before each visit. This may cause:
- Dizziness,
- Headache
- Stomach discomfort
- Fainting
Chemin du Saquin 15G
69130 Ecully
FR
Chemin du Saquin 15G
69130 Ecully
FR
Listed location countries
Age
Inclusion criteria
- A confirmed gentic diganosis of PWS. Documentation of PWS subtype. If PWS
subtype is not known, a sample for testing may be obtained
and the patient may continue on to be enrolled into the study if he/she meets
all the other inclusion criteria and non of the
exclusion criteria.
- Male and female patients 4 to 65 years of age.
- Evidence of increased appetite or hyperphagia, as jugded by the investigator
and HQ-CT score.
- Patient must have a single primary caregiver who should be available for the
duration of the study. On average,
approximately 4 (or more) waking hours per day with the patient.
- BMI * 65 kg/m2
- Growth hormone treatment permitted if doses are stable
Exclusion criteria
- History of chronic liver disease
- Type 1 diabetes mellitus
- HbA1c > 10%
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003062-13-NL |
| ClinicalTrials.gov | NCT03790865 |
| CCMO | NL68543.078.19 |