Clinical Trials Register

Summary
EudraCT Number:	2018-003062-13
Sponsor's Protocol Code Number:	AZP01-CLI-003
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2018-003062-13

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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.

A.3.2

Name or abbreviated title of the trial where available

ZEPHYR

A.4.1

Sponsor's protocol code number

AZP01-CLI-003

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Millendo Therapeutics SAS
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Millendo Therapeutics SAS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Millendo Therapeutics SAS
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	15G Chemin du Saquin
B.5.3.2	Town/ city	Ecully
B.5.3.3	Post code	69130
B.5.3.4	Country	France
B.5.4	Telephone number	+33 472 18 09 30
B.5.6	E-mail	zephyr@millendo.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1932
D.3 Description of the IMP
D.3.1	Product name	Livoletide
D.3.2	Product code	AZP-531
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Livoletide
D.3.9.1	CAS number	1088543-62-7
D.3.9.4	EV Substance Code	SUB170025
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Livoletide
D.3.9.1	CAS number	1088543-62-7
D.3.9.4	EV Substance Code	SUB170025
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	16
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prader-Willi Syndrome

E.1.1.1

Medical condition in easily understood language

Prader-Willi Syndrome

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10036476
E.1.2	Term	Prader-Willi syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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.

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 2b - 3 months
Phase 3 - 6 months

E.5.2

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase 2b - 3 months
Phase 3 - 6 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

E.6.9 Dose response is applicable to Phase 2b only

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

France

Italy

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of study is defined as the last visit of the last patient (LPLV) in the trial globally.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1