Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome

Study Overview
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Brief Summary
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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).

Detailed Description
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The protocol includes 2 consecutive parts: The first part is a Phase 2b dose-response study consisting of a 3-month double-blind, placebo-controlled Core Period followed by a 9-month Extension Period. The second part is a Phase 3 study consisting of a 6-month double-blind, placebo-controlled Core Period followed by a 6-month Extension Period. Phase 3 may be initiated following review of safety and efficacy results at the completion of the Phase 2b Core Period. A total of approximately 50 patients per group (8 to 65 years of age) will be randomized (approximately 150 patients in total). In addition to this cohort of 150 patients, a separate cohort of patients 4 to 7 years of age will also be randomized. Note: The 8-65 year old cohort has been fully enrolled. Enrollment into the 4-7 year age cohort remains ongoing.

Official Title
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A Phase 2b/3 Study to Evaluate the Safety, Tolerability, and Effects of Livoletide (AZP-531), an Unacylated Ghrelin Analogue, on Food-related Behaviors in Patients With Prader-Willi Syndrome

Conditions
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Prader-Willi Syndrome, Hyperphagia

Intervention / Treatment
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* Drug: Livoletide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed genetic diagnosis of PWS Evidence of increased appetite or hyperphagia Patient must have a single primary caregiver who should be available for certain durations of the study BMI ≤ 65 kg/m2 Growth hormone treatment permitted if doses have been stable for at least 1 month prior to screening Exclusion Criteria: History of chronic liver disease Type 1 diabetes mellitus HbA1c > 10% Body weight <20 kg

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose Livoletide<br>Daily subcutaneous injection of   60 mcg/kg for 3 month double-blind core period and 9 month open label extension period. | Drug: Livoletide<br>* Daily subcutaneous injection<br>* Other names: AZP-531;|
| Experimental: High-Dose Livoletide<br>Daily subcutaneous injection of  120 mcg/kg for 3 month double-blind core period and 9 month open label extension period. | Drug: Livoletide<br>* Daily subcutaneous injection<br>* Other names: AZP-531;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Daily subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT) | 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. | Baseline to month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese | Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings. Overweight/obese patients were defined as follows: patients ≥18 years of age: BMI ≥27 kg/m2 patients 4-17 years of age: BMI ≥90th percentile for the same age and sex | Baseline to month 3 | 
| Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese | The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007. Overweight/obese patients were defined as follows: patients ≥18 years of age: BMI ≥27 kg/m2 patients 4-17 years of age: BMI ≥90th percentile for the same age and sex | Baseline to month 3 | 
| Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese | Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible. Overweight/obese patients were defined as follows: patients ≥18 years of age: BMI ≥27 kg/m2 patients 4-17 years of age: BMI ≥90th percentile for the same age and sex | Baseline to month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prader-Willi Syndrome, PWS