Clinical Trials Register

Summary
EudraCT Number:	2015-001578-17
Sponsor's Protocol Code Number:	SHP-GCB-402
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

2015-001578-17

A.3

Full title of the trial

An Open-label, Multicenter, Single-arm, Phase 4 Study of the Effect of
Treatment with Velaglucerase alfa on Bone-related Pathology in
Treatment-naïve Patients with Type 1 Gaucher Disease

Studio di fase 4 in aperto, multicentrico, a braccio singolo per valutare l'effetto del trattamento con
Velaglucerasi alfa sulla patologia ossea in pazienti affetti da malattia di Gaucher di tipo 1 mai trattati in precedenza

A.3.1

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

An Open-Label, Phase IV Study of Velaglucerase alfa on Bone Related Pathology in Adult, Treatment-Naïve Patients with Type 1 Gaucher Disease

Studio in aperto di fase IV di valutazione di Velaglucerasi alfa nelle patologie ossee in pazienti adulti, affetti da malattia di Gaucher di tipo 1 mai trattati in precedenza.

A.3.2

Name or abbreviated title of the trial where available

SHP-GCB-402

A.4.1

Sponsor's protocol code number

SHP-GCB-402

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

A.5.4

Other Identifiers

Name:

Number:

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	SHIRE HUMAN GENETIC THERAPIES, INC
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	Shire Human Genetic Therapies, Inc.
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	Shire
B.5.2	Functional name of contact point	Steven A. Johnson Jr.
B.5.3	Address:
B.5.3.1	Street Address	300 Shire Way
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	MA02421
B.5.3.4	Country	United States
B.5.4	Telephone number	0017814821525
B.5.5	Fax number	0000000
B.5.6	E-mail	sjohnsonjr0@shire.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	VPRIV - 400 U - POLVERE PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO(VETRO) 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	SHIRE PHARMACEUTICALS IRELAND LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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/3/10/752
D.3 Description of the IMP
D.3.1	Product name	Velaglucerase alfa
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Powder 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.3.8	INN - Proposed INN	velaglucerasi alfa
D.3.9.1	CAS number	884604-91-5
D.3.9.2	Current sponsor code	GA-GCB
D.3.9.3	Other descriptive name	GLUCOCEREBROSIDASE UMANO GENE-ATTIVATO
D.3.9.4	EV Substance Code	SUB31010
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Gaucher Disease

Malattia di Gaucher

E.1.1.1

Medical condition in easily understood language

Gaucher disease is caused by a defective enzyme. Due to this, fatty substances build up in the cells of the body, especially in liver, spleen and bone marrow.

La malatt di Gaucher è provocata da un enzima difettoso. A causa di questo difetto, sostanze grasse si accumulano nelle cell dell'organismo, in particolare nel fegato, nella milza e nel midollo osseo

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	10075697
E.1.2	Term	Gaucher's disease type I
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

To evaluate the effect of VPRIV therapy (60 U/kg every other week [EOW]) in treatment-naïve patients with type 1 Gaucher disease on change from baseline in lumbar spine (LS) bone mineral density (BMD) Z-score as measured by dual energy x-ray absorptiometry (DXA) after 24 months of treatment.

Valutare l'effetto della terapia con VPRIV (60 U/kg a settimane alterne [EOW]) in pazienti mai trattati in precedenza affetti da malattia di Gaucher di tipo 1 sulla variazione rispetto al basale del punteggio Z della DMO (densità minerale ossea) nel tratto lombare della colonna (LS), misurato mediante assorbimento a raggi X a doppia energia (DXA) dopo 24 mesi di trattamento.

E.2.2

Secondary objectives of the trial

To evaluate the effect of VPRIV therapy (60 U/kg EOW) on bone mineral density (BMD) in treatment-naïve patients with type 1 Gaucher disease as measured by the change from baseline in LS BMD Z-score at 12 months, and bone marrow burden (BMB) as measured by magnetic resonance imaging (MRI) of the LS and femur after 12 and 24 months of treatment.

Valutare l'effetto della terapia con VPRIV (60 U/kg EOW) sulla Densità Minerale Ossea (DMO) in pazienti mai trattati in precedenza affetti da malattia di Gaucher di tipo 1 misurata in base alla variazione rispetto al basale del punteggio Z della DMO nella LS a 12 mesi, e al carico del midollo osseo (BMB) misurato mediante RMI della LS e del femore dopo 12 e 24 mesi di trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each patient must meet the following criteria to be enrolled in this study.
1. The patient has a documented diagnosis of type 1 Gaucher disease, as documented by deficient GCB activity in leukocytes (whole blood only) or cultured skin fibroblasts. Diagnosis by dry blood spot test is not sufficient. Diagnosis may be
based on results obtained prior to screening if documented in the patient's medical history.
2. Patients must have a LS BMD Z-score <-1 as measured by DXA during the screening phase.
3. Patient is treatment-naïve, ie, has not received ERT or SRT in the 12 months prior to enrollment.
4. The patient is =18 and =65 years of age.
5. Female patients of childbearing potential must agree to use a medically acceptable method of contraception at all times during the study. (See Section 6.8.3 for acceptable methods of contraception).
6. The patient, or patient's legally authorized representative(s), if applicable, understands the nature, scope, and possible consequences of the study and has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
7. The patient must be sufficiently cooperative to participate in this clinical study as judged by the investigator.

Ogni paziente deve soddisfare i seguenti criteri per essere arruolato in questo studio.
1. Il paziente presenta una diagnosi documentata di malattia di Gaucher di tipo 1, documentata mediante un’attività deficitaria di GCB nei leucociti (solo sangue intero) o fibroblasti cutanei coltivati. La diagnosi ottenuta dall'analisi di una goccia di sangue essiccato non è sufficiente. La diagnosi può basarsi sui risultati ottenuti prima dello screening, se documentata nell'anamnesi medica del paziente.
2. I pazienti devono avere un punteggio Z della DMO della LS <-1 misurato mediante DXA durante la fase di screening.
3. Il paziente è naïve al trattamento, ovvero, non è stato sottoposto a terapie ERT o SRT nei 12 mesi precedenti l'arruolamento.
4. Il paziente ha un'età compresa tra =18 e =65 anni.
5. Le pazienti di sesso femminile in età fertile devono accettare di usare un metodo contraccettivo clinicamente accettabile per tutta la durata dello studio (vedere la Sezione 6.8.3 per i metodi contraccettivi accettabili).
6. Il paziente, o il/i rappresentante/i legalmente autorizzato/i del paziente, ove pertinente, comprende la natura, l'ambito e le possibili conseguenze dello studio e ha fornito il consenso informato scritto che è stato approvato dal Consiglio di Revisione Istituzionale/ Comitato Etico Indipendente (IRB/CEI).
7. Il paziente deve essere sufficientemente cooperante nel partecipare a questo studio clinico secondo il giudizio dello sperimentatore.

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from the study.
1. Neurological symptoms indicating that the patient has type 3 Gaucher disease.
2. A significant comorbidity, which, as determined by the investigator, might affect study data or confound the study results (eg, malignancies, primary biliary cirrhosis, autoimmune liver disease, etc).
3. Any osteoporosis-specific treatment (eg, bisphosphonates) or treatment with erythropoietin (or erythropoietin-like substances) during the past year.
4. Structural, joint-associated bone damage of such extent and severity that the investigator deems it could impact participation in the study and assessment of relevant study endpoints (eg, pain).
5. The patient is pregnant or lactating.
6. The patient has had a splenectomy.
7. The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.
8. Severe vitamin D deficiency to the level that would be expected to result in osteomalacia (25-hydroxyvitamin D < 10 ng/mL [25 nmol/L]). If there is mild vitamin D insufficiency at screening (25-hydroxyvitamin D > 10 and < 30 ng/mL) treat with 4000 IU 25-hydroxyvitamin D per day for 1 month and rescreen.
9. The patient has previously interrupted ERT for safety reasons.
10. The patient has had hypersensitivity to the active substance or to any of the excipients.

I pazienti che rispondono ai seguenti criteri saranno esclusi dallo studio.
1. Sintomi neurologici indicanti che il paziente è affetto da malattia di Gaucher di tipo 3.
2. Una comorbilità significativa che, secondo quanto stabilito dallo sperimentatore, potrebbe influire sui dati dello studio o confondere i risultati dello studio (per esempio tumori maligni, cirrosi biliare primitiva, malattia epatica autoimmune, ecc.).
3. Qualsiasi trattamento specifico per l'osteoporosi (per esempio bifosfonati) o trattamento con eritropoietina (o sostanze simili all’eritropoietina) nell’anno precedente.
4. Danno osseo strutturale, associato alle articolazioni di tale entità e gravità, che lo sperimentatore ritenga possa influire sulla partecipazione allo studio e sulle valutazioni di endpoint rilevanti dello studio (per esempio, dolore).
5. La paziente è in stato di gravidanza o allatta al seno.
6. Il paziente è stato sottoposto a una splenectomia.
7. Il paziente è arruolato in un altro studio clinico che comporta sperimentazioni cliniche o l'uso di qualsiasi prodotto sperimentale (farmaco o dispositivo) entro i 30 giorni precedenti all'arruolamento nello studio o in qualsiasi momento durante lo studio.
8. Grave carenza di vitamina D a un livello che potrebbe causare osteomalacia (25-Idrossivitamina D <10 ng/mL [25 nmol/L]). Se è presente una lieve insufficienza di vitamina D allo screening (25-Idrossivitamina D > 10 e <30 ng/mL), trattare con 4000 IU di 25-Idrossivitamina D al giorno per 1 mese ed eseguire nuovamente lo screening.
9. Il paziente ha precedentemente interrotto l'ERT per motivi di sicurezza.
10. il paziente ha manifestato ipersensibilità al principio attivo o a uno qualsiasi degli eccipienti.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to 24 months (Week 103 [end of study]) in LS BMD Z-score as measured by DXA. Assessments will be performed at the screening visit and Weeks 25, 51,77, and 103 (end of study).

Variazione rispetto al basale a 24 mesi (Settimana 103 [fine dello studio] del punteggio Z della DMO della LS, misurato tramite DXA. Le valutazioni saranno svolte alla visita di screening e alle Settimane 25, 51, 77 e 103 (fine dello studio)

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessments will be performed at the screening visit and Weeks 25, 51, 77, and 103 (end of study).

Le valutazioni saranno svolte alla visita di screening e alle Settimane 25, 51, 77 e 103 (fine dello studio).

E.5.2

Secondary end point(s)

The key secondary endpoints of this study are:
• Change from baseline to 12 months (Week 51) and 24 months (Week 103 [end of study]) in BMB score (MRI of lumbar spine and femur). Assessments will be
performed at the baseline visit and Weeks 25, 51, 77, and 103 (end of study).
• Change from baseline to 12 months (Week 51) in LS BMD Z-score.
Assessments will be performed at the screening visit and Weeks 25, 51, 77, and 103 (end of study).

I principali endpoint secondari di questo studio sono:
• Variazione rispetto al basale a 12 mesi (Settimana 51) e a 24 mesi (Settimana 103 [fine dello studio]) nel punteggio BMB (RMI di tratto lombare e femore). Le valutazioni saranno svolte alla visita basale e alle Settimane 25, 51, 77 e 103 (fine dello studio).
• Variazione rispetto al basale a 12 mesi (Settimana 51) dello Z -score della DMO dell' LS.
Le valutazioni saranno svolte alla visita di screening e alle Settimane 25, 51, 77 e 103 (fine dello studio).

E.5.2.1

Timepoint(s) of evaluation of this end point

. Assessments will be performed at the baseline visit and Weeks 25, 51, 77, and 103 (end of study).
. Assessments will be performed at the screening visit and Weeks 25, 51,77, and 103 (end ofstudy).

Le valutazioni saranno svolte alla visita basale e alle Settimane 25, 51, 77 e 103 (fine dello studio).
Le valutazioni saranno svolte alla visita di screening e alle Settimane 25, 51, 77 e 103 (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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

studio non controllato ma in aperto

study not controlled but open

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Germany

Israel

Italy

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

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)

At the end of the study the patient’s doctor or primary care doctor will discuss the options for continued care

Al termine dello studio il medico del paziente o il medico di base discuteranno le opzioni per la prosecuzione dei trattamenti

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

2016-12-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
Orphan Designation Number:
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