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A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)

Primary Purpose

Glycogen Storage Disease Type IA

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
DTX401
Placebo
Oral corticosteroids
Placebo for oral corticosteroids
Sponsored by
Ultragenyx Pharmaceutical Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glycogen Storage Disease Type IA focused on measuring glycogen storage disorder Ia, AAV, gene therapy, von Gierke disease, glucose metabolism disorder, GSDIa, GSD1

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Documented GSDIa with confirmation by molecular testing or enzymatic activity on liver biopsy
  • Currently receiving a therapeutic regimen of cornstarch (or equivalent) and is clinically stable as evidenced by no more than a 10% change in cornstarch (or equivalent) regimen and no hospitalization for hypoglycemia over a 4 week period
  • Willing and able to complete the informed consent process and to comply with study procedures and visit schedule
  • Females of childbearing potential and fertile males must consent to use highly effective contraception from the period following informed consent through the duration of the 96-week study and in cases of early withdrawal at least 48 weeks after the last dose of investigational product (IP). Female subjects must agree not to become pregnant. Male subjects must agree not to father a child or donate sperm

Key Exclusion Criteria:

  • Detectable pre-existing antibodies to the AAV8 capsid
  • History of liver transplant, including hepatocyte cell therapy/ transplant
  • History of liver disease
  • Presence of liver adenoma >5 cm in size
  • Presence of liver adenoma >3 cm and ≤5 cm in size that has a documented annual growth rate of ≥0.5 cm per year
  • Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN), total bilirubin >1.5 × ULN, alkaline phosphatase >2.5 × ULN
  • Non-fasting triglycerides ≥1000 mg/dL
  • Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study.
  • Current or previous participation in another gene transfer study
  • History of illicit drug use within 60 days prior to screening or positive results from an 8-panel urine drug screen during the Screening Period completed at 2 time points at least 6 weeks apart

Note additional inclusion/exclusion criteria may apply, per protocol

Sites / Locations

  • Children's Hospital of Orange County
  • Children's Hospital Colorado
  • University of Connecticut Health Center
  • Mount Sinai
  • Duke University
  • Cleveland Clinic
  • Children's Hospital of Philadelphia
  • University of Texas
  • Primary Children's Hospital
  • Hospital de Clinicas de Porto Alegre
  • McGill University
  • Righospitalet
  • University Medical Center Eppendorf
  • Istituto Giannina Gaslini
  • University of Naples
  • Groningen University
  • Hospital Clinico Universitario de Santiago

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DTX401, Then Placebo

Placebo, Then DTX401

Arm Description

Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.

Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.

Outcomes

Primary Outcome Measures

Percent Change from Baseline to Week 48 in Daily Cornstarch Intake

Secondary Outcome Measures

Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group
Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L])
Patient Global Impression of Change (PGIC) Assessment Score at Week 48
Change from Baseline to Week 48 in Time to Hypoglycemia (<54 mg/dL [3.0 mmol/L]) During a Controlled Fasting Challenge
Change from Baseline to Week 48 in Percentage of Glucose Values in the Range of 70-120 mg/dL (3.9-6.7 mmol/L)
Number of Treatment Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Serious TEAEs, Related TEAEs, Discontinuations From Study or Investigational Product Due to Adverse Events (AEs), and Fatal AEs

Full Information

First Posted
July 14, 2021
Last Updated
September 8, 2023
Sponsor
Ultragenyx Pharmaceutical Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05139316
Brief Title
A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 8, 2021 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objectives of this study are to evaluate the efficacy of DTX401 to reduce or eliminate dependence on exogenous glucose replacement therapy to maintain euglycemia and to maintain or improve the quality of glucose control.
Detailed Description
Study DTX401-CL301 is a phase 3, randomized, double-blind, placebo-controlled study to determine the efficacy and confirm the safety of DTX401 in patients 8 years and older with glycogen storage disease type Ia (GSDIa). Participants will be randomized 1:1 to DTX401 or placebo group, and followed closely for 48 weeks. At week 48 eligible participants will cross over and receive DTX401 if they had previously received placebo or placebo if they had previously received DTX401, and will be followed closely for an additional 96 weeks. After completion of week 144 or early withdrawal, participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glycogen Storage Disease Type IA
Keywords
glycogen storage disorder Ia, AAV, gene therapy, von Gierke disease, glucose metabolism disorder, GSDIa, GSD1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DTX401, Then Placebo
Arm Type
Experimental
Arm Description
Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
Arm Title
Placebo, Then DTX401
Arm Type
Placebo Comparator
Arm Description
Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
Intervention Type
Genetic
Intervention Name(s)
DTX401
Intervention Description
nonreplicating, recombinant, adeno-associated virus (AAV) serotype 8 (AAV8)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Normal Saline infusion
Intervention Type
Drug
Intervention Name(s)
Oral corticosteroids
Other Intervention Name(s)
prednisolone
Intervention Description
Participants who receive DTX401 solution will receive oral corticosteroids
Intervention Type
Drug
Intervention Name(s)
Placebo for oral corticosteroids
Intervention Description
Participants who receive Placebo will receive placebo oral corticosteroids to maintain the study blind
Primary Outcome Measure Information:
Title
Percent Change from Baseline to Week 48 in Daily Cornstarch Intake
Time Frame
Baseline, Week 48
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group
Time Frame
Baseline, Week 48
Title
Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L])
Time Frame
Baseline, Week 48
Title
Patient Global Impression of Change (PGIC) Assessment Score at Week 48
Time Frame
Baseline, Week 48
Title
Change from Baseline to Week 48 in Time to Hypoglycemia (<54 mg/dL [3.0 mmol/L]) During a Controlled Fasting Challenge
Time Frame
Baseline, Week 48
Title
Change from Baseline to Week 48 in Percentage of Glucose Values in the Range of 70-120 mg/dL (3.9-6.7 mmol/L)
Time Frame
Baseline, Week 48
Title
Number of Treatment Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Serious TEAEs, Related TEAEs, Discontinuations From Study or Investigational Product Due to Adverse Events (AEs), and Fatal AEs
Time Frame
up to 144 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Documented GSDIa with confirmation by molecular testing or enzymatic activity on liver biopsy Currently receiving a therapeutic regimen of cornstarch (or equivalent), following international guidance/recommendations with stable nutrition, glycemic, and clinical status. Willing and able to complete the informed consent process and to comply with study procedures and visit schedule Females of childbearing potential and fertile males must consent to use highly effective contraception from the period following informed consent through the duration of the 144-week study and in cases of early withdrawal at least 48 weeks after the last dose of investigational product (IP). Female subjects must agree not to become pregnant. Male subjects must agree not to father a child or donate sperm Key Exclusion Criteria: Detectable pre-existing antibodies to the AAV8 capsid History of liver transplant, including hepatocyte cell therapy/ transplant History of liver disease Presence of liver adenoma >5 cm in size Presence of liver adenoma >3 cm and ≤5 cm in size that has a documented annual growth rate of ≥0.5 cm per year Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN), total bilirubin >1.5 × ULN, alkaline phosphatase >2.5 × ULN Non-fasting triglycerides ≥1000 mg/dL Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study. Current or previous participation in another gene transfer study History of illicit drug use within 60 days prior to screening or positive results from an 8-panel urine drug screen during the Screening Period completed at 2 time points at least 4 weeks apart Note: additional inclusion/exclusion criteria may apply, per protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
Mount Sinai
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
McGill University
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Righospitalet
City
Kopenhagen
State/Province
Capital
ZIP/Postal Code
2100
Country
Denmark
Facility Name
University Medical Center Eppendorf
City
Hamburg
ZIP/Postal Code
20251
Country
Germany
Facility Name
Istituto Giannina Gaslini
City
Genova
State/Province
Linguria
ZIP/Postal Code
16147
Country
Italy
Facility Name
University of Naples
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Groningen University
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Hospital Clinico Universitario de Santiago
City
Santiago De Compostela
State/Province
A Coruna
ZIP/Postal Code
15706
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://ultrarareadvocacy.com/conditions-we-study/glycogen-storage-disease-type-ia-gsdia/
Description
Ultragenyx Patient Advocacy/GSDIA Disease Information

Learn more about this trial

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)

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