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

Phase 2

Terminated

Conditions: Prader-Willi Syndrome
Hyperphagia

Interventions: Drug: Livoletide
Drug: Placebo

Registration Number: NCT03790865

Lead Sponsor: Millendo Therapeutics SAS

Brief Summary: 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: The protocol includes 2 consecutive parts:

1. 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.

2. 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 158

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-Dose Livoletide	Livoletide	Daily subcutaneous injection of \~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
High-Dose Livoletide	Livoletide	Daily subcutaneous injection of \~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)	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 Measures

Name	Time	Method
Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese	Baseline to month 3	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
Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese	Baseline to month 3	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
Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese	Baseline to month 3	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

Trial Locations

Locations (37): University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Centre Hospitalier Universitaire d'Angers
🇫🇷
Angers, France
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
University of California - Irvine Medical Center
🇺🇸
Orange, California, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Children's Hospital Colorado
🇺🇸
Denver, Colorado, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Boston Children's Hospital
🇺🇸
Boston, Massachusetts, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Children's Hospitals and Clinics of Minnesota-Minneapolis
🇺🇸
Saint Paul, Minnesota, United States
New York Presbyterian Morgan Stanley Children's Hospital
🇺🇸
New York, New York, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Royal Prince Alfred Hospital
🇦🇺
Camperdown, Australia
Austin Health
🇦🇺
Melbourne, Australia
Perth Children's Hospital
🇦🇺
Nedlands, Australia
CHU Lyon - Hopital Femmes Mere Enfant
🇫🇷
Bron, France
The Childrens Hospital at Westmead
🇦🇺
Westmead, Australia
Hospital Pitie Salpetriere
🇫🇷
Paris, France
Hopital Necker-Enfants Malades
🇫🇷
Paris, France
CHU de Toulouse - Hospital Rangueil
🇫🇷
Toulouse, France
Azienda Ospedaliera Universitaria Federico II
🇮🇹
Napoli, Italy
CHU de Toulouse - Hopital des Enfants
🇫🇷
Toulouse, France
Hospital General Universitario de Alicante
🇪🇸
Alicante, Spain
Ospedale Pediatrico Bambino Gesù
🇮🇹
Roma, Italy
Erasmus University Medical Center
🇳🇱
Rotterdam, Netherlands
Stichting Kind en Groei
🇳🇱
Rotterdam, Netherlands
Hospital de Cruces
🇪🇸
Barakaldo, Spain
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
🇪🇸
Sabadell, Spain
NHS Tayside
🇬🇧
Dundee, United Kingdom
Hospital Sant Joan de Deu
🇪🇸
Barcelona, Spain
Chelsea and Westminster Hospital
🇬🇧
London, United Kingdom
Imperial College London
🇬🇧
London, United Kingdom
Cliniques Universitaires Saint-Luc
🇧🇪
Brussels, Belgium
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States