Clinical Trials Register

Summary
EudraCT Number:	2016-003023-30
Sponsor's Protocol Code Number:	401GSDIA01
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-01
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

Netherlands - Competent Authority

A.2

EudraCT number

2016-003023-30

A.3

Full title of the trial

A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV)Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase (G6Pase) in Adults with Glycogen Storage Disease Type Ia (GSDIa)

A.3.1

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

An early-phase clinical study of a vector transferring the gene for Glucose-6-Phosphatase (G6Pase) in adults with Glycogen Storage Disease Type Ia.

A.4.1

Sponsor's protocol code number

401GSDIA01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03517085

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	Ultragenyx Pharmaceutical, 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	Ultragenyx Pharmaceutical, 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	Ultragenyx Pharmaceutical, Inc.
B.5.2	Functional name of contact point	Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	840 Memorial Drive
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617 714 0704

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/3/16/1771
D.3 Description of the IMP
D.3.1	Product name	DTX401
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet assigned.
D.3.9.2	Current sponsor code	DTX401
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	5000000000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	Classified as gene therapy medicinal product, EMA/506999/2016
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	Yes
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

Glycogen Storage Disease Type Ia (GSDIa).

E.1.1.1

Medical condition in easily understood language

Inherited disorder causing decrease of glucose.

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10056911
E.1.2	Term	Glycogen storage disease type IA
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 safety of single IV doses of DTX401 in adults with GSDIa, including the incidence of dose-limiting toxicities (DLTs).

E.2.2

Secondary objectives of the trial

To establish a dose of DTX401 that achieves symptom-free euglycemia (glucose ≥60 mg/dL
[≥3.33 mmol/L]) in a setting of a controlled fasting challenge to allow further clinical development.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Willing and able to provide written informed consent.
2. Males and females ≥18 years of age.
3. Documented GSDIa with confirmation by molecular testing.
4. Documented history of ≥1 hypoglycemic event with glucose <60 mg/dL (<3.33 mmol/L).
5. Subject’s GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit.
6. Hematology and coagulation panel results are within the normal range or, if outside the normal range, are deemed not clinically significant in the opinion of the investigator.
7. No known allergic reaction to any component of DTX401.
8. Willing and able to comply with study procedures and requirements, including periodic inpatient hospitalization, frequent blood collections, and 24-hour urine collection.
9. Males and females of childbearing potential must be willing to use effective contraception at the time of administration of DTX401 and for 52 weeks following administration of DTX401 to prevent the potential transmission of the AAV vector.

E.4

Principal exclusion criteria

1. Screening or Baseline (Day 0) glucose level <60 mg/dL (<3.33 mmol/L); subjects may be
rescreened after glucose is controlled and stable, at the discretion of the investigator.
2. Liver transplant, including hepatocyte cell therapy/transplant.
3. Presence of liver adenoma >5 cm in size.
4. Presence of liver adenoma >3 cm and ≤5 cm in size that has a documented annual growth rate of ≥0.5 cm per year.
5. Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase > the upper limit of normal (ULN), total bilirubin >1.5 × ULN, or alkaline phosphatase >2.5 × ULN. Liver function tests may be repeated during the screening period at the investigator’s discretion.
6. Serum creatinine >2.0 mg/dL.
7. Triglycerides ≥1000 mg/dL at the time of the screening visit.
8. Presence of active, or history of treatment for, hepatitis B virus or hepatitis C virus infection.
9. History of human immunodeficiency virus infection AND any of the following: CD4+ cell count <350 cells/mm3, change in antiretroviral therapy regimen within 6 months prior to
Day 0, or viral load >200 copies/mL, on 2 separate occasions, as measured by polymerase chain reaction.
10. History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer treated with watchful waiting or surgically removed nonmelanoma skin cancer.
11. Active infection (viral or bacterial).
12. Anti-AAV8 neutralizing antibody titer ≥1:5.
13. Participation (current or previous) in another gene transfer study.
14. Participation in another investigational product study within 3 months of Screening.
15. Has a positive serum pregnancy test at Screening (females of childbearing potential only), a positive urine pregnancy test at Baseline (Day 0; females of childbearing potential only), or is nursing.
16. Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.

E.5 End points

E.5.1

Primary end point(s)

The incidence of AEs, including the incidence of DLTs at each dose level, TEAEs, and SAEs for each dosing cohort, assessed by severity and relationship to study product.

E.5.1.1

Timepoint(s) of evaluation of this end point

From the time the subject signs the Informed Consent Form (ICF) up to 30 days after the end of study

E.5.2

Secondary end point(s)

The change from baseline in time (in minutes) to first hypoglycemic event (defined as glucose <60 mg/dL [<3.33 mmol/L]) during a controlled fasting challenge at 6, 12, 24, and 52 weeks after IV administration of DTX401.

E.5.2.1

Timepoint(s) of evaluation of this end point

6, 12, 24 and 54 weeks after IV administration of DTX401

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

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)

Yes

E.7.1.1

First administration to humans

Yes

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.8.3

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

Canada

Netherlands

Spain

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

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)

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

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)

After patients have ended their participation in the trial, they will be treated according to the normal standard of care. After completion of this study, subjects will be offered enrollment in a 4-year extension study to evaluate the long-term (a total of 5 years) safety and efficacy of DTX401.

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

2018-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-02

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