Clinical Trials Register

Summary
EudraCT Number:	2013-002257-30
Sponsor's Protocol Code Number:	AT2220-017
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-10-21
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

UK - MHRA

A.2

EudraCT number

2013-002257-30

A.3

Full title of the trial

AN OPEN-LABEL SAFETY AND DOSE-FINDING STUDY OF INTRAVENOUS DUVOGLUSTAT CO-ADMINISTERED WITH RECOMBINANT HUMAN ACID α-GLUCOSIDASE IN SUBJECTS WITH POMPE DISEASE

A.3.1

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

A dose finding study with intravenous administration of duvoglustat hydrochloride (AT2220) and Myozyme in Pompe patients

A.4.1

Sponsor's protocol code number

AT2220-017

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	Amicus Therapeutics, 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	Amicus Therapeutics, 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	Amicus Therapeutics, Inc.
B.5.2	Functional name of contact point	Patient Advocacy
B.5.3	Address:
B.5.3.1	Street Address	30 A Upper High Street
B.5.3.2	Town/ city	Thame Oxon
B.5.3.3	Post code	OX9 3EX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	16096622000
B.5.5	Fax number	16096625010
B.5.6	E-mail	clinicaltrials@amicusrx.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	duvoglustat hydrochloride
D.3.2	Product code	AT2220
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	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	duvoglustat HCl
D.3.9.1	CAS number	73285-50-4
D.3.9.2	Current sponsor code	AT2220 HCl
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	30.6
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	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	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.IMP: 2
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	Myozyme
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe B.V., Gooimeer 10, 1411 DD, Naarden, The Netherlands
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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/3/01/018
D.3 Description of the IMP
D.3.1	Product name	Myozyme
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 drip use (Noncurrent)
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.3.9.4	EV Substance Code	SUB21275
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.5 to 4
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

Pompe disease

E.1.1.1

Medical condition in easily understood language

Pompe disease is an enzyme deficiency which results in buildup of glycogen, primarily in muscle cells, that leads to a progressive loss of muscle function.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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 evaluate the safety of intravenous (IV) duvoglustat administered immediately before and at point(s) during and after IV infusion of recombinant human acid α glucosidase (rhGAA);
To determine the optimal dose and administration regimen of IV duvoglustat based on plasma, urine, and muscle pharmacokinetics (PK) of IV duvoglustat

E.2.2

Secondary objectives of the trial

To evaluate the effects of IV duvoglustat on plasma rhGAA activity

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male or female, diagnosed with Pompe disease and between 16 and 65 years of age, inclusive (where required by local authorities, the minimum age will be 18 years of age)
2.Subject has never been treated with rhGAA (rhGAA-naïve)
OR Subject has been treated with Lumizyme (rhGAA-experienced) for at least 12 months, AND for at least the 12 weeks before the Screening Visit, has been consistently treated with Lumizyme as per its local commercial labeling (or as per local regulations, with prior approval of the sponsor), including being on a stable dose, with a stable infusion duration (between 3 and 5 hours) and biweekly schedule (stable defined as not varying by more than ± 10%)
For subjects who fall outside of these criteria, entry into the clinical trial is at the sponsor’s discretion
3.Subject, whether male or female, agrees to use medically accepted methods of contraception during the study and for 30 days after their last administration of duvoglustat (unless subject is not of childbearing potential)
4.Subject is willing and able to provide written informed consent and, as applicable, assent. Subjects under 18 years of age will provide written informed assent, and written informed consent will be provided by their parent or legal guardian
5.Subject is able to comply with all study procedures

E.4

Principal exclusion criteria

1.Subject has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 12 weeks before the Screening Visit
2.Subject has clinically significant unstable cardiac disease (ie, any cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or NYHA class III or IV congestive heart failure)
3.Subject requires any invasive mechanical ventilation
4.Subject is restricted to a wheelchair or is otherwise not fully ambulatory; subjects who require wheelchair assistance or walkers under special circumstances may be eligible at the discretion of the sponsor
5.Subject has a history of allergy or sensitivity to study drug (including excipients) or other iminosugars (eg, miglitol, miglustat)
6.Subject is pregnant or breastfeeding
7.Subject has a positive medical history for hepatitis A, B, or C, or HIV (human immunodeficiency virus)
8.Subject has received any investigational/experimental device within the 30 days before the Screening Visit
9.Subject is taking, or has taken at any time in the 12 weeks before the Screening Visit, a prohibited medication [miglitol (eg, Glyset); acarbose (eg, Precose, Glucobay); voglibose (eg, Volix, Vocarb, Volibo); oseltamivir (eg, Tamiflu); dietary supplements containing mulberry extract; chloroquine; any investigational/experimental drug]
10.Subject is taking, or has taken at any time in the 26 weeks before the Screening Visit, the prohibited medication miglustat (eg, Zavesca)
11.Subject is taking, or has taken at any time in the 12 months before the Screening Visit, any immunosuppressant drug (eg, cyclosporins, azathioprines, methotrexate, monoclonal antibodies that block the immune system, and long-term corticosteroids). Subjects who require corticosteroids for acute management of infusion reactions may be allowed with sponsor approval
12.Subject has any concurrent illness or condition that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the subject may have an unacceptable risk by participating in this study

E.5 End points

E.5.1

Primary end point(s)

For the primary study objective of evaluating the safety of IV duvoglustat the parameters are as follows: adverse events (AEs), clinical laboratory evaluations (serum chemistry, hematology, and urinalysis), concomitant medications, ECGs, physical examination, weight, vital signs, 6MWT, and FVC

For the primary study objective of determining the optimal dose and administration regimen of IV duvoglustat, it will be based on plasma, urine, and muscle PK of IV duvoglustat.

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study.

E.5.2

Secondary end point(s)

For the secondary study objective of evaluating the effects of IV duvoglustat on plasma rhGAA activity, the parameters will be as specified in the SAP.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study.

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

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

E.8.1.2

Open

Yes

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

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.8.5

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

Netherlands

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

Database lock. Amicus relies on the use of bioanalytical endpoints that are assessed at multiple specialty labs. These data are not captured on the CRF. Analyzing and summarizing all these lab data takes considerably longer than the standard 12 months from LSLV due to the complexity of sample analyses. As such, the appropriate definition of EoT needs to be marked by database lock, which allows time needed to merge the bioanalyical data with the CRF data.

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)

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Patients 16 - 17 years of age.

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

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

2013-11-14

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-12-06

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