Clinical Trials Register

Summary
EudraCT Number:	2016-000942-77
Sponsor's Protocol Code Number:	EFC14028
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:	2018-02-06
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

2016-000942-77

A.3

Full title of the trial

A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of NeoGAA (GZ402666) and Alglucosidase Alfa in Treatmentnaïve Patients with Late-onset Pompe Disease

Studio randomizzato di fase 3, multicentrico, internazionale, in doppio cieco, per il confronto dell’efficacia e della sicurezza di infusioni ripetute ogni due settimane di neoGAA (GZ402666) e alglucosidasi alfa in pazienti naïve al trattamento con malattia di Pompe a esordio tardivo

A.3.1

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

Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies neoGAA and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease

Studio per il confronto dell’efficacia e
della sicurezza della terapia di sostituzione enzimatica neoGAA e alglucosidasi alfa somministrati una volta ogni due settimane in
pazienti con malattia di Pompe a esordio tardivo mai precedentemente trattati per la malattia di Pompe

A.3.2

Name or abbreviated title of the trial where available

COMET

A.4.1

Sponsor's protocol code number

EFC14028

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1178-4806

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	SANOFI S.p.A.
B.5.2	Functional name of contact point	CONTACT POINT
B.5.3	Address:
B.5.3.1	Street Address	VIALE BODIO, 37/B
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.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/3/14/1251
D.3 Description of the IMP
D.3.1	Product name	neoGAA
D.3.2	Product code	GZ402666
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1802558-87-7
D.3.9.2	Current sponsor code	GZ402666
D.3.9.3	Other descriptive name	α-glucosidasi acida umana ricombinante coniugata con multiple copie di bis-mannosio-6- fosfato-tetra-mannosio glicano sintetico (NEOGAA)
D.3.9.4	EV Substance Code	SUB120294
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	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	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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	MYOZYME®
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe B.V.
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/00/018
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALGLUCOSIDASE ALFA
D.3.9.1	CAS number	420784-05-0
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB21275
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	50
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	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

Pompe disease (acid alpha-glucosidase deficiency)

Malattia di Pompe (deficit di alfa-glucosidosi acido)

E.1.1.1

Medical condition in easily understood language

Treatment of enzyme deficiency in glycogen storage disease type II (Pompe disease)

Trattamento del deficit enzimatico in glicogenosi di tipo II (malattia di Pompe)

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	LLT
E.1.2	Classification code	10036143
E.1.2	Term	Pompe's disease
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

To determine the effect of neoGAA (GZ402666) treatment on respiratory muscle strength measured by percent predicted forced vital capacity (% FVC) in the upright position, as compared to alglucosidase alfa.

Determinare l’effetto del trattamento con neoGAA sulla forza della muscolatura respiratoria,
misurata come percentuale predetta della capacità vitale forzata (FVC) in posizione eretta, rispetto ad alglucosidasi alfa.

E.2.2

Secondary objectives of the trial

To determine the safety and effect of neoGAA treatment on inspiratory muscle strength (maximum inspiratory pressure [MIP]), expiratory muscle strength (maximum expiratory pressure [MEP]), unctional endurance (6-minute walk test[6MWT]), lower extremity muscle strength (hand-held dynamometry [HHD]), motor function (Quick Motor Function Test [QMFT]), and health-related quality of life (SF-12).

Determinare la sicurezza e l’effetto del trattamento con neoGAA sulla forza della muscolatura
inspiratoria (pressione inspiratoria massima [MIP]),sulla forza della muscolatura espiratoria (pressione espiratoria massima [MEP]),
sulla resistenza funzionale (test del cammino dei 6 minuti [6-minute walk test, 6MWT]), sulla forza della muscolatura delle estremità inferiori
(dinamometria manuale [hand-held dynamometry, HHD]), sulla funzionalità motoria (Test rapido della funzione motoria [Quick Motor Function Test, QMFT]) e sulla qualità della vita correlata alla salute (modulo breve a 12 voci [Short Form-12, SF-12]).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-The patient has confirmed GAA enzyme deficiency from any tissue source and/or 2 confirmed GAA gene mutations.
-The patient and/or their parent/legal guardian is willing and able to provide signed informed consent, and the patient, if <18 years of age, is willing to provide assent if deemed able to do so.
-The patient (and patient’s legal guardian if patient is <18 years of age) must have the ability to comply with the clinical protocol.
-The patient, if female and of childbearing potential, must have a negative pregnancy test (betahuman chorionic gonadotropin) at baseline.

- Il paziente presenta un deficit dell’enzima GAA confermato a partire da qualsiasi fonte di tessuto e/o 2 mutazioni confermate del
gene GAA.
-Il paziente e / o i loro genitori / tutori legali sono disposti e in grado di fornire e firmare il consenso informato, e il paziente, se ha
meno di 18 anni di età, è disposto a fornire l'assenso se ritenuto in grado di farlo.
-Il paziente ( e tutore legale del paziente se il paziente è <18 anni di età) deve avere la capacità di rispettare il protocollo clinico.
-Il paziente, se di sesso femminile e in età fertile, deve avere un test di gravidanza negativo (beta-gonadotropina corionica umana)
al basale

E.4

Principal exclusion criteria

-The patient is <3 years of age.
-The patient has known Pompe specific cardiac hypertrophy.
-The patient is wheelchair dependent.
-The patient is not able to ambulate 40 meters (approximately 130 feet) without topping and without an assistive device.
-The patient requires invasive-ventilation (non-invasive ventilation is allowed).
-The patient is not able to successfully perform repeated forced vital capacity (FVC) measurements in upright position of ≥40% predicted and ≤85% predicted.
-The patient has had previous treatment with alglucosidase alfa or any investigational therapy for Pompe disease.
-The patient has prior or current use of immune tolerance induction therapy

- Il paziente ha <3 anni di età
- il paziente presenta un’ipertrofia cardiaca nota
specifica della malattia di Pompe
- il paziente è dipendente dalla sedia a rotelle
- il paziente non è in grado di camminare per 40 metri (circa 130 piedi) senza fermarsi e senza un dispositivo di assistenza
- il paziente richiede una ventilazione invasiva (la ventilazione non invasiva è consentita)
- il paziente non è in grado di eseguire con successo misurazioni ripetute della FVC in posizione eretta ≥40% del predetto e ≤85%
del predetto
- il paziente ha ricevuto un precedente trattamento con alglucosidasi alfa o qualsiasi terapia sperimentale per la malattia di Pompe
- Il paziente ha fatto uso in precedenza, o sta facendo uso, di una terapia di induzione della tolleranza immunologica

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in percent predicted
forced vital capacity (%FVC) in upright position

Variazione della % predetta di FVC in posizione eretta

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to 12 months

dal basale a 12 mesi

E.5.2

Secondary end point(s)

Change from baseline in maximal
inspiratory pressure in upright position
Change from baseline in maximal expiratory pressure in upright position
Change from baseline in six-minute walk test scores
Change from baseline in hand-held dynamometry measurement
Change from baseline in Quick Motor Function Test scores
Change from baseline in 12- Item Short-form health survey scores

Variazione rispetto al basale della massima pressione inspiratoria in posizione eretta
Variazione rispetto al basale della pressione espiratoria massima in posizione eretta
Variazione rispetto al basale del punteggio del test del cammino dei 6 minuti
Variazione rispetto al basale della misurazione con dinamometria manuale
Variazione rispetto al basale del punteggio del test rapido della funzionalità motoria
Variazione rispetto al basale del punteggio del modulo breve a 12 voci sulla qualità della salute

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to 12 months

dal basale a 12 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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

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)

Yes

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

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

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

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)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

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

Patients <18 years of age

I pazienti <18 anni di età

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)

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

2016-08-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-08-01

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

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