Clinical Trials Register

Summary
EudraCT Number:	2014-004415-37
Sponsor's Protocol Code Number:	NN8022-4179
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:	2015-07-29
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

2014-004415-37

A.3

Full title of the trial

Effect of liraglutide for weight management in paediatric subjects with Prader-Willi Syndrome. A randomised, placebo controlled, parallel group, multi-centre, multinational trial with a 16-week double-blind period and 36-week open-label period

Effetto di liraglutide nella gestione del peso in pazienti pediatrici affetti da Sindrome di Prader-Willi. Studio Clinico randomizzato, controllato con placebo, a gruppi paralleli, multicentrico, internazionale con un periodo in doppio cieco di 16 settimane e un periodo in aperto di 36 settimane

A.3.1

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

Effect of liraglutide for weight management in children with Prader-Willi Syndrome

Effetto di liraglutide nella gestione del peso in pazienti pediatrici affetti da Sindrome di Prader-Willi.

A.4.1

Sponsor's protocol code number

NN8022-4179

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1162-7884

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/086/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novo Nordisk A/S
B.1.3.4	Country	Denmark
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	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Global Clinical Registry (GCR,1452)
B.5.3	Address:
B.5.3.1	Street Address	Novo Allé
B.5.3.2	Town/ city	Bagsværd
B.5.3.3	Post code	2880
B.5.3.4	Country	Denmark
B.5.6	E-mail	clinicaltrials@novonordisk.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	Yes
D.2.1.1.1	Trade name	Saxenda
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
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	LIRAGLUTIDE
D.3.9.1	CAS number	204656-20-2
D.3.9.4	EV Substance Code	SUB25238
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	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Obesity
(Prader-Willi syndrome)

Obesità
(Sindrome di Prader-Willi)

E.1.1.1

Medical condition in easily understood language

Abnormal or excessive body fat accumulation/excess proportion of total body fat
(Prader-Willi syndrome)

Accumulo anormale o eccessivo di grasso corporeo/ eccesso nella proporzione del grasso corporeo totale
(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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10029883
E.1.2	Term	Obesity
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of liraglutide versus placebo on weight loss in obese paediatric subjects with Prader-Willi syndrome (PWS) at 16 weeks and versus no treatment at 52 weeks

Verificare l’efficacia di liraglutide relativamente alla perdita di peso in soggetti pediatrici obesi affetti da PWS (sindrome di Prader-Willi) dopo 16 settimane di trattamento in confronto al placebo e dopo 52 settimane di trattamento in assenza di confronto.

E.2.2

Secondary objectives of the trial

1. To compare the efficacy of liraglutide versus placebo on glycaemic control in obese children and adolescents with PWS at 16 weeks and versus no treatment at 52 weeks.
2. To estimate the liraglutide steady state exposure in obese children and adolescents with PWS after 16 weeks of treatment.
3. To compare the safety of liraglutide versus placebo in obese children and adolescents with PWS at 16 weeks and versus no treatment at 52 weeks.

1. Verificare l’efficacia di liraglutide in confronto al placebo sul controllo glicemico in bambini ed adolescenti obesi affetti da PWS dopo 16 settimane e in confronto a nessun trattamento dopo 52 settimane.
2. Fare una stima dello steady state dell’esposizione a liraglutide in bambini e adolescenti obesi affetti da PWS dopo 16 settimane di trattamento.
3. Verificare la sicurezza di liraglutide in confronto al placebo in bambini e adolescenti obesi affetti da PWS dopo 16 settimane e in confronto a nessun trattamento dopo 52 settimane.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Confirmed diagnosis of PWS (by genetic testing)
3. Male or female, age at the time of signing informed consent:
– Part A: ≥ 12 and < 18 years
– Part B: ≥ 6 and < 12 years
4. Tanner stage 2−5 pubertal development for part A, and Tanner stage 1 for part B
5. BMI corresponding to ≥ 30 kg/m^2 for adults by international cut-off points and ≥ the 95th percentile for age and sex (for diagnosis of obesity)
6. Stable body weight during the previous 90 days before screening (< 10 kg self-reported weight change)
7. Testing has been performed to evaluate for adrenal insufficiency and documented in medical record

1. Firma del modulo di consenso informato ottenuto prima di qualsiasi attività correlata allo studio clinico. Per attività correlate allo studio si intende qualunque procedura effettuato nell’ambito dello studio, incluse le attività per valutare la partecipazione allo studio.
2. Diagnosi confermata di sindrome Prader Willi (PWS) documentata mediante esami genetici
3. Maschi o Femmine con un età al momento della firma del modulo di consenso informato:
Parte A: ≥ 12 e < 18 anni
Parte B: ≥ 6 e < 12 anni
4. Sviluppo puberale secondo lo stadio 2-5 di Tanner per la Parte A e di stadio 1 di Tanner per la Parte B
5. BMI che corrisponda a ≥ 30 kg/m2 per gli adulti secondo i punti di cut-off internazionali1 e ≥ 95° percentile secondo età e sesso (per la diagnosi di obesità)
6. Peso corporeo stabile nel corso degli ultimi 90 giorni precedenti lo screening (variazione di peso inferiori ai 10 kg)
7. Aver effettuato il test per la valutazione del l’insufficienza surrenalica, documentato in cartella clinica

E.4

Principal exclusion criteria

1. Type 1 diabetes mellitus (T1DM)
2. Type 2 diabetes mellitus (T2DM)
3. Calcitonin ≥ 50 ng/L
4. No change in treatment plan with growth hormone (GH) from randomisation to the end of the open-label period patients on growth hormone to stay on, patients off GH to stay off during this period. Adjustments in doses of growth hormone will be permitted)
5. Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroids Carcinoma (MTC)
6. History of pancreatitis (acute or chronic)
7. Treatment with any medication prescribed for weight loss within 90 days before screening (e.g. orlistat, zonisamide, topiramate/phentermine, lorcaserin, phentermine, bupropion/naltrexone, liraglutide, metformin)
8. Untreated adrenal insufficiency

1. Diabete mellito di tipo 1
2. Diabete mellito di tipo 2
3. Calcitonina ≥ 50 ng/l
4. Nessun cambiamento nel piano di trattamento con ormone della crescita (GH) dalla randomizzazione alla fine del periodo in aperto (i pazienti in terapia con ormone della crescita dovranno rimanere in terapia, i pazienti che non effettuano terapia con ormone della crescita non dovranno iniziare la terapia ormonale. Aggiustamenti nella dose di ormone della crescita sono permessi).
5. Anamnesi familiare o personale di neoplasia endocrina multipla di tipo 2 (Multiple Endocrine Neoplasia Type 2, MEN 2) o carcinoma midollare della tiroide (Medullary Thyroids Carcinoma,MTC)
6. Storia di pregressa pancreatite (acuta o cronica)
7. Trattamento con qualsiasi farmaco prescritto per la perdita di peso entro 90 giorni precedenti lo screening (ad esempio, orlistat, zonisamide, topiramato/fentermina, lorcaserin, fentermina, bupropione/naltrexone, liraglutide, metformina)
8. Insufficienza surrenalica non trattata

E.5 End points

E.5.1

Primary end point(s)

1. Change in body mass index (BMI) standard deviation score (SDS)
2. Change in body mass index (BMI) standard deviation score (SDS)

1. Standard Deviation Score (SDS) della variazione dell’indice di massa corporea (BMI)
2. Standard Deviation Score (SDS) della variazione dell’indice di massa corporea (BMI)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From baseline to 16 weeks
2. From baseline to 52 weeks

1. dal valore basale a 16 settimane
2. dal valore basale a 52 settimane

E.5.2

Secondary end point(s)

1. Percent of subjects achieving ≥ 5% reduction in baseline BMI
2. Percent of subjects achieving ≥ 10% reduction in baseline BMI

Change in:
3. BMI
4. Body weight (kilogram (kg), pounds (lb) and percent (%))
5. Hyperphagia score:
a. total score and
b. hyperphagic behaviour, drive and severity score
6. Systolic and diastolic blood pressure
7. Glucose metabolism: glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG)

1. Percentuale di soggetti che hanno raggiunto una riduzione ≥ 5% del BMI basale
2. Percentuale di soggetti che hanno raggiunto una riduzione ≥ 10% del BMI basale

Variazione dei seguenti parametri:
3. BMI
4. Peso corporeo (chilogrammo (kg), libbre (lb) e percentuale (%))
5. Valutazione dell’iperfagia:
a. punteggio totale e
b. punteggio relativo al comportamento iperfagico, agli impulsi e alla sua gravità.
6. Pressione sanguigna sistolica e diastolica
7. Metabolismo del glucosio: emoglobina glicosilata (HbA1c), glicemia a digiuno (Fasting Plasma Glucose, FPG)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. - 2.: At weeks 16 and 52
3. - 7.: From baseline to 16 and 52 weeks

1. - 2.: Alle settimane 16 e 52
3. - 7.: Dal valore basale a 16 ed a 52 settimane

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

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

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

Tolerability

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)

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

Yes

E.8.1.7.1

Other trial design description

Periodo in doppio-cieco di 16 settimane seguito da un periodo in aperto di 36 settimane

Double-blind period followed by open-label period

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

Australia

Canada

European Union

New Zealand

Turkey

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

LVLS

Ultima visita dell'ultimo Paziente (LVLS)

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

Number of subjects for this age range:

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)

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

Yes

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

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

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)

N/A

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

2015-11-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-10

P. End of Trial
P.	End of Trial Status	Completed

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