Clinical Trials Register

Summary
EudraCT Number:	2018-003062-13
Sponsor's Protocol Code Number:	AZP01-CLI-003
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-10-07
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

Italy - Italian Medicines Agency

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

Studio di fase 2b/3 per valutare la sicurezza, la tollerabilità e gli effetti di livoletide (AZP-531), un analogo della grelina deacilata, sui comportamenti alimentari in pazienti affetti da sindrome di Prader-Willi

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.

Studio clinico in pazienti affetti da sindrome di Prader-Willi per valutare se un farmaco chiamato livoletide può ridurre il comportamento alimentare correlato ed essere sicuro e ben tollerato.

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	0033472180930
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	D.3.2 Product code where applicable13:
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.3.9.1	CAS number	1088543-62-7
D.3.9.2	Current sponsor code	na
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	8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1088543-62-7
D.3.9.2	Current sponsor code	na
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Sindrome di Prader-Willi

E.1.1.1

Medical condition in easily understood language

Prader-Willi Syndrome

Sindrome di Prader-Willi

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	SOC
E.1.2	Classification code	10010331
E.1.2	Term	Congenital, familial and genetic disorders
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.

PERIODO CENTRALE
Fase 2b
Dimostrare l’efficacia di un trattamento di 3 mesi con livoletide rispetto a placebo per ridurre il comportamento alimentare osservato dal caregiver come valutato in base al Questionario sull’iperfagia per le sperimentazioni cliniche (Hyperphagia Questionnaire for Clinical Trials, HQ-CT).

Fase 3
Dimostrare l’efficacia di un trattamento di 6 mesi con livoletide rispetto a placebo per ridurre il comportamento alimentare osservato dal caregiver come valutato in base all’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

PERIODO CENTRALE
Fase 2b
• Dimostrare l’efficacia di un trattamento di 3 mesi con livoletide rispetto a placebo per:
¿ ridurre la massa grassa corporea totale in pazienti con SPW sovrappeso/obesi;
¿ ridurre la circonferenza vita (waist circumference, WC) in pazienti con SPW sovrappeso/obesi;
¿ ridurre il peso corporeo (body weight, BW) in pazienti con SPW sovrappeso/obesi.

Fase3
• Dimostrare l’efficacia di un trattamento di 6 mesi con livoletide rispetto a placebo per:
¿ ridurre la massa grassa corporea totale in pazienti con SPW sovrappeso/obesi;
¿ ridurre la WC in pazienti con SPW sovrappeso/obesi;
¿ ridurre il BW in pazienti con SPW sovrappeso/obesi.

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.

FASE 2b e 3 (PERIODO CENTRALE)
1. Diagnosi di SPW confermata mediante test di metilazione dell’acido desossiribonucleico (DNA)
2. Pazienti maschi e femmine di età da 8 a 65 anni, compresi.
3. Evidenza di aumento di appetito o iperfagia

FASE 2b e 3 estensione
Per poter partecipare al Periodo di estensione, i pazienti dovranno aver completato il Periodo centrale.

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.

PERIODO CENTRALE
FASE 2b
1. Anamnesi di epatopatia cronica, come cirrosi o epatite cronica da qualsiasi causa, o sospetto abuso di alcol.
2. Anamnesi di malattia cardiovascolare significativa, compresa un’anamnesi di insufficienza cardiaca congestizia (ICC, di classe 3 o 4 secondo la New York Heart Association [NYHA] [Associazione dei cardiologi di New York]), angina pectoris o infarto del miocardio (myocardial infarction, MI) entro 6 mesi prima dello screening.
3. Diabete mellito di tipo 1
4. Emoglobina glicata (hemoglobin A1C, HbA1C) >10%.

Fase 3
I pazienti arruolati nella parte di fase 2b non sono idonei all’arruolamento nella parte di fase 3.

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.

PERIODO CENTRALE DI FASE 2b
Variazione dal basale alla fine del Periodo centrale di 3 mesi nel punteggio HQ-CT totale.

FASE 3
Variazione dal basale alla fine del Periodo centrale di 6 mesi nel punteggio HQ-CT totale.

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 2b - 3 months
Phase 3 - 6 months

Fase 2b - 3 mesi
Fase 3 - 6 mesi

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.

PERIODO CENTRALE DI FASE 2b
• Variazione percentuale dal basale alla fine del Periodo centrale di 3 mesi nella massa grassa corporea totale in pazienti con SPW sovrappeso/obesi.
• Variazione dal basale alla fine del Periodo centrale di 3 mesi nella WC in pazienti con SPW sovrappeso/obesi.
• Variazione percentuale dal basale alla fine del Periodo centrale di 3 mesi nel BW in pazienti con SPW sovrappeso/obesi.

Fase 3
• Variazione percentuale dal basale alla fine del Periodo centrale di 6 mesi nella massa grassa corporea totale in pazienti con SPW sovrappeso/obesi.
• Variazione dal basale alla fine del Periodo centrale di 6 mesi nella WC in pazienti con SPW sovrappeso/obesi.
• Variazione percentuale dal basale alla fine del Periodo centrale di 6 mesi nel BW in pazienti con SPW sovrappeso/obesi.

E.5.2.1

Timepoint(s) of evaluation of this end point

Phase 2b - 3 months
Phase 3 - 6 months; Fase 2b - 3 mesi
Fase 3 - 6 mesi

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

Dose response is applicable to Phase 2b only

Studio dose-risposta applicabile solo alla Fase 2b

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)

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

Information not present in EudraCT

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

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.

LPLV dello studio

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Some adults subjects with PWS are not able to consent. Patients will be assented after legal guardian/parents has signed the Consent.

Alcuni soggetti adulti con PWS non sono in grado di acconsentire. I pazienti acconsentiranno dopo che il tutore legale / i genitori hanno firmato il consenso.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nessuno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-03-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-05-25

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