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

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

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 Overview

• Status: Terminated
• Conditions: Hyperphagia; Prader-Willi Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Livoletide

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.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Melbourne, Australia, 3084
    • Austin Health
  • Nedlands, Australia, 6009
    • Perth Children's Hospital
  • Westmead, Australia, 2145
    • The Childrens Hospital at Westmead
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc
• France
  • Angers, France, 49100
    • Centre Hospitalier Universitaire d'Angers
  • Bron, France, 69677
    • CHU Lyon - Hopital Femmes Mere Enfant
  • Paris, France, 75015
    • Hôpital Necker-Enfants Malades
  • Paris, France, 75013
    • Hospital Pitie Salpetriere
  • Toulouse, France
    • CHU de Toulouse - Hôpital des Enfants
  • Toulouse, France, 31059
    • CHU de Toulouse - Hospital Rangueil
• Italy
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambino Gesu
• Netherlands
  • Rotterdam, Netherlands, 3015
    • Erasmus University Medical Center
  • Rotterdam, Netherlands, 3016
    • Stichting Kind en Groei
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barakaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu
  • Sabadell, Spain, 08208
    • Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • NHS Tayside
  • London, United Kingdom, W12 0NN
    • Imperial College London
  • London, United Kingdom, SW109NH
    • Chelsea and Westminster Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Orange, California, United States, 92868
      • University of California - Irvine Medical Center
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Children's Hospitals and Clinics of Minnesota-Minneapolis
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • New York Presbyterian Morgan Stanley Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Livoletide; Daily subcutaneous injection; Other Names: AZP-531
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.	Drug: Livoletide; Daily subcutaneous injection; Other Names: AZP-531
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.	Drug: Placebo; Daily subcutaneous injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Millendo Therapeutics SAS

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): May 25, 2020

Study Registration Dates

• First Submitted: December 28, 2018
• First Submitted That Met QC Criteria: December 28, 2018
• First Posted (Actual): January 2, 2019

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Prader-Willi Syndrome; PWS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Signs and Symptoms, Digestive; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Hyperphagia
• Other Study ID Numbers: AZP01-CLI-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No