Clinical Trials Register

Summary
EudraCT Number:	2022-002323-35
Sponsor's Protocol Code Number:	TAK-669-3001
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2022-11-10
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2022-002323-35

A.3

Full title of the trial

A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Velaglucerase Alfa in Chinese Subjects With Type 1 Gaucher Disease

A.3.1

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

A Study of Velaglucerase Alfa (VPRIV) in Chinese Children, Teenagers, and Adults With Type 1 Gaucher Disease

A.4.1

Sponsor's protocol code number

TAK-669-3001

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	Takeda Development Center Americas, 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	Takeda
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	Takeda Development Center America, Inc.
B.5.2	Functional name of contact point	Clinical Transparency
B.5.3	Address:
B.5.3.1	Street Address	95 Hayden Ave
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	MA02421
B.5.3.4	Country	United States
B.5.6	E-mail	ClinicalTransparency@takeda.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
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire Pharmaceuticals Ireland Ltd
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/3/10/752
D.3 Description of the IMP
D.3.1	Product name	Velaglucerase alfa (VPRIV)
D.3.2	Product code	GA-GCB
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.3.11 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	Yes
D.3.11.13.1	Other medicinal product type	Recombinant gene activated protein derived from a human cell line by insertion of regulatory structural DNA sequences into the glucocerebrosidase locus

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

Type 1 Gaucher Disease

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 the liver, spleen, and bone marrow.

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

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 of the study is to evaluate the safety of VPRIV by assessing the incidence of serious treatment-emergent AEs (TEAEs) when administered every other week (EOW) up to 51 weeks by intravenous (IV) infusion to Chinese subjects with type 1 Gaucher disease.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study include assessing:
- Other safety parameters of VPRIV (including the incidence of TEAEs and infusion-related reactions (IRRs) and rates of antibody formation)
- The effect of VPRIV on hematologic manifestations
- The effect of VPRIV on the liver and spleen volume
- The effect of VPRIV on quality of life (QoL)
- The pharmacokinetic (PK) of VPRIV
- The effect of VPRIV on disease biomarkers

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Has a documented, confirmed diagnosis of type 1 Gaucher disease based on the following, as determined by the investigator: a. Decreased glucocerebrosidase (GCB) activity level that is ≤30% of normal; or b. Decreased GCB activity level that is >30% of normal, but with confirmation of genetic mutation test
- Is at least 2 years of age, inclusive, at screening
- Is naive to treatment for Gaucher disease (Has not received treatment for Gaucher disease [investigational or approved products] within the 12 months prior to screening) OR Is receiving or has recently received Imiglucerase ERT (Has received Imiglucerase treatment within the 12 months prior to screening and not within the 14 days prior to screening)
- Has Gaucher disease-related hematological abnormalities, defined as: a. Hemoglobin levels of ≥1 g/dL below the lower limit of normal for their age and gender AND/OR b. A platelet count of <90 × 109/L below the lower limit of normal for their age and gender
- Has Gaucher disease-related viscera abnormalities, defined as the following: Participant has at least moderate splenomegaly, assessed by palpation (2 to 3 cm below the left costal margin), or by abdominal radiology scan (magnetic resonance imaging [MRI] or computed tomography [CT] scan, with spleen volume >5 times normal) AND/OR Participant has hepatomegaly, assessed by palpation or by abdominal radiology scan (MRI or CT scan); Participants who have undergone splenectomy must have satisfied these criteria for this study.

E.4

Principal exclusion criteria

- Has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease as assessed by the investigator
- Has had a splenectomy or an active, clinically significant spleen infarction within the 12 months prior to screening
- Has received treatment with any investigational drug or device within 30 days prior to screening, or within 5 half-lives of that investigational product, whichever is greater; such treatment during the study will not be permitted
- Is currently receiving red blood cell growth factor (eg, erythropoietin), chronic systemic corticosteroids, or has been on such treatment within the 6 months prior to screening
- Has a positive test result at screening for hepatitis B surface antigen (HBsAg) with detectable hepatitis B viral DNA load, hepatitis C virus (HCV) antibody with confirmation by HCV RNA polymerase chain reaction testing, and HIV antibody
- Presents with non-Gaucher disease related exacerbated anemia at screening (eg, due to iron, folic acid, and/or vitamin B12 deficiency or infectious/immune-mediated causes). Participants who have a folic acid deficiency, vitamin B12-deficiency-related anemia, or iron-deficiency-related anemia during screening do not meet the study entry criteria and will be considered a screening failure. Participants may be treated for the underlying disease and be rescreened as judged by investigator. Rescreening will be permitted once only
- Participant, participant’s parent(s), or participant’s legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
- Has a significant comorbidity, in the opinion of the investigator, that might affect the study data or confound the study results (eg, malignancies, primary biliary cirrhosis, or autoimmune liver disease)
- Is unable to comply with the protocol (eg, has a clinically relevant medical condition making implementation of the protocol difficult, an uncooperative attitude, is unable to return to the site for safety evaluations, or is otherwise unlikely to complete the study), as determined by the investigator
- Has experienced a severe (grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any ERT (approved or investigational). Note: Participants with a historical positive antibody result to Imiglucerase but without a severe infusion-related hypersensitivity reaction will not be excluded

E.5 End points

E.5.1

Primary end point(s)

Percentage of Participants With at Least One Serious Treatment-
Emergent Adverse Events (TEAE) Throughout the Study

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 59 weeks

E.5.2

Secondary end point(s)

1 - Percentage of Participants With TEAEs
2 - Percentage of Participants With Infusion-related Reactions
Throughout the Study Reported as Adverse Event
3 - Percentage of Participants With Development of anti-VPRIV
Antibodies, Including Neutralizing Antibody Status Throughout the
Study
4 - Number of Participants With Clinically Significant Changes in
Laboratory Assessments, Vital Signs Measurements, and
Electrocardiogram (ECG) Measurements
5 - Change from Baseline to Week 53 in Hemoglobin Concentration
6 - Change from Baseline to Week 53 in Platelet Count
7 - Change from Baseline to Week 53 in Normalized Liver Volume
8 - Change from Baseline to Week 53 in Normalized Spleen Volume
9 - Change from Baseline to Week 53 in Quality of Life (QoL)
Questionnaire Assessment as Measured by Short Form-36 (SF-36),
Version 2
10 - Change from Baseline to Week 53 in QoL Questionnaire
Assessment as Measured by Childhood Health Questionnaire-Parent
Form 50 (CHQ-PF50)
11 - Cmax: Maximum Observed Serum Concentration for VPRIV at
Week 1
12 - Cmax: Maximum Observed Serum Concentration for VPRIV at
Week 37
13 - Tmax: Time to Reach the Maximum Serum Concentration (Cmax)
for VPRIV
14 - AUCinf: Area Under the Plasma Concentration-time Curve from
Time 0 to Infinity for VPRIV
15 - Terminal Phase Elimination Half-life (T1/2) for VPRIV
16 - Oral Clearance (CL) for VPRIV
17 - Apparent Steady-state Volume of Distribution (Vss) for VPRIV
18 - Percentage Change from Baseline to Week 53 in Biomarker:
Plasma Chemokine [C-C motif] Ligand
19 - Percentage Change from Baseline to Week 53 in Biomarker:
Glucosylsphingosine

E.5.2.1

Timepoint(s) of evaluation of this end point

1 - 4 - Up to 59 weeks
5 - 10 - Baseline, up to Week 53
11 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
12 - Post-dose (up to 60 minutes) of Week 37
13 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
14 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
15 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
16 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
17 - Pre-dose and at multiple timepoints (up to 120 minutes) postdose
on Day 1 of Week 1
18 - Baseline, up to Week 53
19 - Baseline, up to Week 53

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

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)

Yes

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

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

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1