Clinical Trials Register

Summary
EudraCT Number:	2010-023953-12
Sponsor's Protocol Code Number:	DFI12712
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:	2013-09-24
Trial 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

2010-023953-12

A.3

Full title of the trial

A Phase 2, Multi-Center, Randomized, Open-Label, Repeat Dose, Dose-Comparison Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Recombinant Human Acid Sphingomyelinase in Patients With Acid Sphingomyelinase Deficiency

Studio multicentrico di confronto delle dosi di fase 2, randomizzato, in aperto, a dosi ripetute, per valutare la sicurezza, l’efficacia e la farmacocinetica della sfingomielinasi acida ricombinante umana in pazienti con carenza di sfingomielinasi acida.

A.3.1

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

Safety, Efficacy, and Pharmacokinetics Study of Recombinant Human Acid Sphingomyelinase in Patients With Acid Sphingomyelinase Deficiency

Sicurezza, Efficacia e Analisi di Farmacocinetica della sfingomielinasi acida ricombinante umana in pazienti con carenza di sfingomielinasi acida.

A.3.2

Name or abbreviated title of the trial where available

ASCEND

A.4.1

Sponsor's protocol code number

DFI12712

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	Genzyme Corporation
B.1.3.4	Country	United States
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	Genzyme Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genzyme Europe B.V.
B.5.2	Functional name of contact point	Medical Information
B.5.3	Address:
B.5.3.1	Street Address	Gooimeer 10
B.5.3.2	Town/ city	Naarden
B.5.3.3	Post code	NL-1411 DD
B.5.3.4	Country	Netherlands
B.5.6	E-mail	eumedinfo@genzyme.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/3/01/056
D.3 Description of the IMP
D.3.1	Product name	rhASM
D.3.2	Product code	GZ402665
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	927883-84-9
D.3.9.2	Current sponsor code	GZ402665
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN ACID SPHINGOMYELINASE (rhASM)
D.3.9.4	EV Substance Code	SUB75088
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	20
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with acid sphingomyelinase deficiency (Niemann-Pick Type B disease)

Pazienti con carenza di sfingomielinasi acida (Malattia Niemann-Pick Tipo B)

E.1.1.1

Medical condition in easily understood language

Patients with Niemann-Pick Type B disease

Pazienti con malattia di Niemann-Pick Tipo B

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10041515
E.1.2	Term	Sphingomyelin lipidosis
E.1.2	System Organ Class	100000004850

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

The primary objective is to evaluate the safety, efficacy, and pharmacokinetics of different doses of rhASM administered intravenously (IV) every 2 weeks for 52 weeks.

L’obiettivo primario di questo studio è valutare la sicurezza, l’efficacia e la farmacocinetica di dosi differenti di sfingomielinasi acida ricombinante umana (rhASM), somministrata per via endovenosa ogni 2 settimane per 52 settimane.

E.2.2

Secondary objectives of the trial

Non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients with documented non-neuronopathic acid sphingomyelinase deficiency
• The patient has a diffusing capacity of carbon monoxide (DLco) >20% and ≤80% of the predicted normal value.
• The patient has a spleen volume ≥6 multiples of normal(MN). A partial splenectomy will be permitted if performed ≥1 year prior to Screening/Baseline and residual spleen volume is ≥6 MN.
• The patient who is female and of childbearing potential must have a negative serum pregnancy test for β-HCG.

Pazienti con documentata deficienza di sfingomielinasi acida non neuropatica
Capacità di diffusione del polmone per il monossido di carbonio >20% e ≤ 80% del normale valore predittivo.
Volume della milza ≥ 6 volte il volume normale. Una splenectomia parziale sarà consentita se eseguita ≥ 1 anno prima della visita di screening e il volume residuale della milza sia ≥ 6 del normale.
Per pazienti donne e in età fertile devono avere Test sierico di gravidanza per le BhcG negativo.

E.4

Principal exclusion criteria

• The patient is female and pregnant or lactating.
• The patient has received an investigational drug within 30 days prior to study enrollment
• The patient has a medical condition or any extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
• The patient has had a major organ transplant
• ALT or AST >250 IU/L or total bilirubin >1.5 mg/dL.
• The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each rhASM infusion for the duration of the study.
• The patient requires medications that may decrease rhASM
• The patient is unwilling or unable to avoid the use of medications or herbal supplements that may cause or prolong bleeding, or have potential hepatotoxicity within 10 days prior to and 3 days after liver biopsy

Paziente donna incinta o in allattamento.
Il/La paziente abbia assunto un farmaco sperimentale nei 30 giorni precedenti l’arruolamento in studio.
Condizione medica o altra circostanza che potrebbe interferire significativamente con l’aderenza allo studio, ivi incluse tutte le valutazioni e le attività di follow-up prescritte.
Il /la paziente abbia subito un trapianto di organo
Valori di alanina aminotransferasi o aspartato aminotransferasi >250 IU/L o di bilirubina totale >1.5 mg/dL.
Il/la paziente non vuole o non è in grado di astenersi dall’assunzione di alcool nel giorno precedente e nei 3 giorni successivi ad ogni infusione di rhASM per la durata dell’intero studio.
Il/la paziente richiede cure mediche che decrescano il rhASM
Il/la paziente non vuole o non è in grado di evitare l’assunzione di farmaci o di integratori a base di erbe che possano causare sanguinamento, o epatotossicità potenziale nei 10 giorni precedenti e nei 3 giorni successivi alla biopsia del fegato.

E.5 End points

E.5.1

Primary end point(s)

Percentage change in spleen volume

Variazione in percentuale del volume della milza

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to end of study

Dal basale alla fine dello studio

E.5.2

Secondary end point(s)

Liver volume
Pulmonary imaging and function testing
Exercise capacity by cycle ergometry
Hematology
Physician Global Assessment
Efficacy biomarkers

• diagnostica per immagini polmonare
• test di funzionalità polmonare
• test da sforzo con bicicletta ergometrica
• ematologia
• valutazione medica globale
• biomarkers di efficacia

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to end of study

Dal basale alla fine dello studio

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

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

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Brazil

Chile

France

Germany

Italy

Tunisia

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

Last visit of the last subject

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.1.1