Clinical Trials Register

Summary
EudraCT Number:	2022-002514-16
Sponsor's Protocol Code Number:	AC-056C405
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2022-07-29
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

Expand All Collapse All

A. Protocol Information

A.2

EudraCT number

2022-002514-16

A.3

Full title of the trial

A single-arm uncontrolled 12-month Clinical Study to evaluate the Safety and Efficacy of miglustat (Zavesca®) for the Treatment of Niemann-Pick Disease Type C (NPC) in Chinese subjects

A.3.1

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

A Clinical Study to evaluate the Safety and Efficacy of miglustat (Zavesca®) for the treatment of Niemann-Pick Disease Type C (NPC) in Chinese subjects

A.4.1

Sponsor's protocol code number

AC-056C405

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03910621

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	Actelion Pharmaceuticals Trading (Shanghai) Co., Ltd
B.1.3.4	Country	China
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	Janssen Research & Development, LLC
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	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Zavesca (Miglustat)
D.2.1.1.2	Name of the Marketing Authorisation holder	Actelion Registration Ltd
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Miglustat
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Miglustat
D.3.9.1	CAS number	72599-27-0
D.3.9.3	Other descriptive name	Zavesca
D.3.9.4	EV Substance Code	SUB20049
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	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.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

Niemann-Pick Disease Type C (NPC)

E.1.1.1

Medical condition in easily understood language

Niemann-Pick Type C is a rare and inherited disease in which quantities of fatty substances accumulate in the brain and other organs. The brain, central nervous system, liver and spleen are affected.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10029403
E.1.2	Term	Niemann-Pick disease
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

The primary objective is to evaluate the efficacy of miglustat on the rate of disease progression and disease stabilization in subjects with NPC.

E.2.2

Secondary objectives of the trial

The secondary objectives are:
1. To assess the effect of miglustat on other aspects of NPC disease control.
2. To assess the safety and tolerability of miglustat in subjects with NPC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in the study, all of the following inclusion criteria must be fulfilled. It is not permitted to waive any of these criteria for any subject:

1. Signed and dated ICF for adult subjects and signed and dated ICF by the parent(s) or legally designated representative AND assent from developmentally capable children.
2. Subjects with confirmed two pathogenic mutations in either NPC1 or NPC2 or one pathogenic mutation in either NPC1 or NPC2 plus a positive biomarker (oxysterol or lysosphingolipids or bile acids) plus high clinical suspicion of disease.
3. Male and female subjects aged 4 years and older.
4. Subjects who can perform the tests for the horizontal and vertical saccadic eye movements;
5. Subjects who are able to swallow the study drug;
6. Women of childbearing potential are only eligible if the following applies:
• Negative urine pregnancy test at screening.
• Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation.
• Agreement to use one of the methods of birth control / follow the contraception scheme from screening up to at least 30 days after study treatment discontinuation.
7. A fertile male (physiologically capable of fathering a child according to investigator’s judgment) is eligible only if he agrees to use a condom during intercourse for the treatment period and for an additional 12 weeks after treatment discontinuation.

E.4

Principal exclusion criteria

Subjects must not fulfill any of the following exclusion criteria. It is not permitted to waive any of these criteria for any subject:

1. Subjects suffering from clinically significant diarrhea (> 3 liquid stools per day for > 7 days) without definable cause within 3 months before enrollment.
2. Known hypersensitivity to the investigational treatment or drugs of the same class, or any of their excipients.
3. Subjects who suffer from renal insufficiency with a creatinine clearance rate of < 30 ml/min per 1.73 m^2.
4. Pregnant, planning to be become pregnant, or lactating females, not using reliable birth control male adult subjects.
5. Previous exposure to investigational treatment for more than 12 months before study start.
6. Treatment with eliglustat, benzodiazepine and any other drug potentially influencing eye movements and the outcomes of the Pineda score
7. Planned or current treatment with another investigational treatment up to 3 months prior to randomization. Symptomatic therapies are allowed (such as curcumin).
8. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease, end stage disease including wheelchair-bound subjects, bedridden subjects etc.
9. Subjects who are judged unqualified for the clinical trial by the investigator.
10. Subjects who suffer lysosomal storage diseases, enzyme deficiency or neurological diseases other than NPC.
11. Subjects who suffer from variant filipin staining without confirmatory genetic diagnosis of NPC.
12. Subjects with uncontrolled epilepsy.
13. Subjects with complete ophthalmoplegia.
14. Known concomitant life-threatening disease with a life expectancy of < 12 months.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is:
The changes in horizontal saccadic eye movements from baseline to Week 52 (Visit 7 / End of Treatment [EOT]).

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

E.5.2

Secondary end point(s)

Efficacy end point:
1. The change in the scores of the Pineda disability scale from Baseline
(Visit 2) to Week 26 (Visit 5) and to Week 52 (Visit 7 / EOT).

Safety endpoints:
2. Treatment-emergent adverse events (AEs) and serious AEs up to 30 days after study treatment discontinuation.
3. Treatment-emergent AEs leading to premature discontinuation of study treatment.
4. Change in vital signs (systolic and diastolic arterial blood pressure and pulse rate), body weight and height from Baseline (Visit 2) to all assessed time points during the study.
5. Treatment-emergent marked laboratory abnormalities up Week 52 / Visit 7 / EOT.
6. Change in laboratory parameters from Baseline (Visit 2) to all assessed time points during the study.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary time points:
1. Baseline (Visit 2) to Week 26 (Visit 5) and to Week 52 (Visit 7 / EOT).

Safety Timepoints:
2,3,4 and 6. Throughout the study
5. Week 52 / Visit 7 / EOT.

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

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, Biomarker evaluation

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

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

China

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.8.9.2

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

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)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Assent must be obtained from study participants who are developmentally capable.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

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)

Post-treatment observation period: Starts on the day after the last dose of study treatment and ends 30 days thereafter with the End of Study Visit.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Peking University First Hospital
G.4.3.4	Network Country	China
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Xinhua Hospital affiliated to Shanghai
G.4.3.4	Network Country	China
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Jiaotong University School of Medicine
G.4.3.4	Network Country	China

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	China

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials