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

Primary Purpose

Prader-Willi Syndrome, Hyperphagia

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Livoletide
Placebo
Sponsored by
Millendo Therapeutics SAS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prader-Willi Syndrome focused on measuring Prader-Willi Syndrome, PWS

Eligibility Criteria

4 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University of California - Irvine Medical Center
  • Rady Children's Hospital - San Diego
  • Children's Hospital Colorado
  • University of Kansas Medical Center
  • Johns Hopkins University
  • Boston Children's Hospital
  • University of Michigan
  • Children's Hospitals and Clinics of Minnesota-Minneapolis
  • Winthrop University Hospital
  • New York Presbyterian Morgan Stanley Children's Hospital
  • Vanderbilt University Medical Center
  • University of Texas Southwestern Medical Center
  • Baylor College of Medicine
  • Seattle Children's Hospital
  • Royal Prince Alfred Hospital
  • Austin Health
  • Perth Children's Hospital
  • The Childrens Hospital at Westmead
  • Cliniques Universitaires Saint-Luc
  • Centre Hospitalier Universitaire d'Angers
  • CHU Lyon - Hopital Femmes Mere Enfant
  • Hospital Pitie Salpetriere
  • Hopital Necker-Enfants Malades
  • CHU de Toulouse - Hospital Rangueil
  • CHU de Toulouse - Hopital des Enfants
  • Azienda Ospedaliera Universitaria Federico II
  • Ospedale Pediatrico Bambino Gesù
  • Erasmus University Medical Center
  • Stichting Kind en Groei
  • Hospital General Universitario de Alicante
  • Hospital de Cruces
  • Hospital Sant Joan de Deu
  • Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
  • NHS Tayside
  • Chelsea and Westminster Hospital
  • Imperial College London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Low-Dose Livoletide

High-Dose Livoletide

Placebo

Arm Description

Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.

Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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

Full Information

First Posted
December 28, 2018
Last Updated
February 8, 2021
Sponsor
Millendo Therapeutics SAS
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1. Study Identification

Unique Protocol Identification Number
NCT03790865
Brief Title
Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome
Acronym
ZEPHYR
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviors
Study Start Date
March 25, 2019 (Actual)
Primary Completion Date
February 26, 2020 (Actual)
Study Completion Date
May 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millendo Therapeutics SAS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prader-Willi Syndrome, Hyperphagia
Keywords
Prader-Willi Syndrome, PWS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
158 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low-Dose Livoletide
Arm Type
Experimental
Arm Description
Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
Arm Title
High-Dose Livoletide
Arm Type
Experimental
Arm Description
Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Livoletide
Other Intervention Name(s)
AZP-531
Intervention Description
Daily subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Daily subcutaneous injection
Primary Outcome Measure Information:
Title
Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)
Description
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.
Time Frame
Baseline to month 3
Secondary Outcome Measure Information:
Title
Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Description
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
Time Frame
Baseline to month 3
Title
Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Description
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
Time Frame
Baseline to month 3
Title
Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Description
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
Time Frame
Baseline to month 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of California - Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Children's Hospital Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota-Minneapolis
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
New York Presbyterian Morgan Stanley Children's Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
ZIP/Postal Code
2050
Country
Australia
Facility Name
Austin Health
City
Melbourne
ZIP/Postal Code
3084
Country
Australia
Facility Name
Perth Children's Hospital
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
The Childrens Hospital at Westmead
City
Westmead
ZIP/Postal Code
2145
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Centre Hospitalier Universitaire d'Angers
City
Angers
ZIP/Postal Code
49100
Country
France
Facility Name
CHU Lyon - Hopital Femmes Mere Enfant
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Hospital Pitie Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU de Toulouse - Hospital Rangueil
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
CHU de Toulouse - Hopital des Enfants
City
Toulouse
Country
France
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Erasmus University Medical Center
City
Rotterdam
ZIP/Postal Code
3015
Country
Netherlands
Facility Name
Stichting Kind en Groei
City
Rotterdam
ZIP/Postal Code
3016
Country
Netherlands
Facility Name
Hospital General Universitario de Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital de Cruces
City
Barakaldo
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital Sant Joan de Deu
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
NHS Tayside
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
Chelsea and Westminster Hospital
City
London
ZIP/Postal Code
SW109NH
Country
United Kingdom
Facility Name
Imperial College London
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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