A Clinical Study in patients with Prader-Willi-Syndrome (PWS) to test if a study drug named livoletide can reduce food related behaviour and be safe and well tolerated.

• Register: EUCTR
• Last refreshed on: 23 November 2020
• Main ID: EUCTR2018-003062-13-FR
• Date of registration: 21/11/2018
• Prospective Registration: Yes
• Primary sponsor: Millendo Therapeutics SAS
• Public title: A Clinical Study in patients with Prader-Willi-Syndrome (PWS) to test if a study drug named livoletide can reduce food related behaviour and be safe and well tolerated.
• Scientific title: A Phase 2b/3 study to evaluate the safety, tolerability, and effects of livoletide (AZP-531), an unacylated ghrelin analog, on food-related behaviors in patients with Prader-Willi syndrome - ZEPHYR
• Date of first enrolment: 25/02/2020
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003062-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Millendo Therapeutics SAS

• Name: Clinical Trial Information
• Affiliation: Millendo Therapeutics SAS

Key inclusion & exclusion criteria

Inclusion criteria:
Phase 2b and Phase 3 Core
1. Diagnosis of PWS confirmed by deoxyribonucleic acid (DNA) methylation test.
2. Male and female patients 8 to 65 years of age, inclusive.
3. Have evidence of increased appetite or Hyperphagia

Phase 2b and 3 Extension
Patients must have participated in the core period.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Core Period
Phase 2b
1. History of chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or suspected alcohol abuse.
2. History of significant cardiovascular disease including history of congestive heart failure CHF, New York Heart Association [NYHA] Class 3 or 4), angina pectoris, or
myocardial infarction (MI) within 6 months prior to screening.
3. Type 1 diabetes mellitus.
4. Glycated hemoglobin (HbA1c) >10%.
5. History of frequent hypoglycaemia.


Phase 3
A patient who enrolled in the Phase 2b part is not eligible for recruitment in the Phase 3 part.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Prader-Willi Syndrome
MedDRA version: 20.0 Level: PT Classification code 10036476 Term: Prader-Willi syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Livoletide
Product Code: AZP-531
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Livoletide
CAS Number: 1088543-62-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
INN or Proposed INN: Livoletide
CAS Number: 1088543-62-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 16-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase 2b - 3 months
Phase 3 - 6 months

Main Objective: Core Period
Phase 2b
To demonstrate the efficacy of a 3-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT).

Phase 3
To demonstrate the efficacy of a 6-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by HQ-CT.

Primary end point(s): Core Period
Phase 2b
• Change from baseline to the end of the 3-month Core Period in HQ-CT total score.

Phase 3
• Change from baseline to the end of the 6-month Core Period in HQ-CT total score.

Secondary Objective: Core Period
Phase 2b
To demonstrate the efficacy of 3-month treatment with livoletide as compared to placebo for:
- Reducing total body fat mass in overweight/obese patients with PWS;
- Reducing waist circumference (WC) in overweight/obese patients with PWS;
- Reducing body weight (BW) in overweight/obese patients with PWS.

Phase 3
To demonstrate the efficacy of 6-month treatment with livoletide as compared to placebo for:
- Reducing total body fat mass in overweight/obese patients with PWS;
- Reducing WC in overweight/obese patients with PWS;
- Reducing BW in overweight/obese patients with PWS.

Extension period:
- Maintenance of effects
- Pharmacokinetics

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase 2b - 3 months
Phase 3 - 6 months

Secondary end point(s): Core Period
Phase 2b
• 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 from baseline to the end of the 3-month Core Period in waist circumference in overweight/obese patients with PWS;
• Percentage change from baseline to the end of the 3-month Core Period in body weight in overweight/obese patients with PWS

Phase 3
• Percentage change from baseline to the end of the 6-month Core Period in total body fat mass in overweight/obese patients with PWS;
• Change from baseline to the end of the 6-month Core Period in waist circumference in overweight/obese patients with PWS;
• Percentage change from baseline to the end of the 6-month Core Period in body weight in overweight/obese patients with PWS.

Secondary ID(s)

AZP01-CLI-003

Source(s) of Monetary Support

Millendo Therapeutics SAS

Ethics review

Status: Approved
Approval date: 25/02/2020
Contact: