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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05139316

Enrollment

Registered

2021-12-01

Start date

2021-11-08

Completion date

2026-02-20

Last updated

2026-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Glycogen Storage Disease Type IA

Keywords

glycogen storage disorder Ia, AAV, gene therapy, von Gierke disease, glucose metabolism disorder, GSDIa, GSD1

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 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 were randomized 1:1 to DTX401 or placebo group and followed closely for 48 weeks. At week 48 eligible participants crossed over and received DTX401 if they had previously received placebo or placebo if they had previously received DTX401 and were followed closely for an additional 96 weeks. After completion of week 144 or early withdrawal, participants were offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion. In Japan, there was a single open label study arm and all participants were treated with DTX401. At week 48, Japanese participants were offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion.

Interventions

GENETICDTX401

nonreplicating, recombinant, adeno-associated virus (AAV) serotype 8 (AAV8)

OTHERPlacebo

Normal Saline infusion

DRUGOral prednisolone

Participants who receive DTX401 solution will receive oral prednisolone

DRUGPlacebo for oral prednisolone

Participants who receive placebo will receive placebo oral prednisolone to maintain the study blind

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

8 Years to No maximum

Healthy volunteers

Inclusion 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/

Design outcomes

Primary

Measure	Time frame	Description
Main Study: Percent Change From Baseline to Week 48 in Daily Cornstarch Intake (Grams)	Baseline, Weeks 24, 30, 36, 42 and 48	The least square (LS) mean and standard error (SE) are based on mixed-model for repeated measures (MMRM) analysis.
Japan Cohort: Percent Change From Baseline to Week 48 in Daily Cornstarch Intake (Grams)	Baseline, Weeks 24, 30, 36, 42 and 48	—

Secondary

Measure	Time frame	Description
Main Study: Change From Baseline to Week 48 in Number of Total Daily Doses of Cornstarch	Baseline, Weeks 24, 30, 36, 42 and 48	The LS mean and SE are based on MMRM analysis.
Japan Cohort: Change From Baseline to Week 48 in Number of Total Daily Doses of Cornstarch	Baseline, Weeks 24, 30, 36, 42 and 48	—
Main Study: Change From Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (Less Than (<) 70 Milligrams Per Deciliter (mg/dL) [3.9 Millimoles Per Liter (mmol/L)])	Baseline, Weeks 24, 30, 36, 42 and 48	The LS mean and SE are based on MMRM analysis.
Japan Cohort: Change From Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (< 70 mg/dL [3.9 mmol/L])	Baseline, Weeks 24, 30, 36, 42 and 48	—
Main Study: Patient Global Impression of Change (PGIC) Assessment Score at Week 48	Week 48	The PGIC captures the participants' perspective on changes in their glycogen storage disease type Ia (GSDIa) since the start of the study using a 7-point response scale ranging from much improved (+ 3) to much worse (- 3). The total score ranges from + 3 to - 3, with a higher score indicating best outcome.
Japan Cohort: PGIC Assessment Score at Week 48	Week 48	The PGIC captures the participants' perspective on changes in their GSDIa since the start of the study using a 7-point response scale ranging from much improved (+ 3) to much worse (- 3). The total score ranges from + 3 to - 3, with a higher score indicating best outcome.
Main Study: Change From Baseline to Week 48 in Time to Hypoglycemia (< 54 mg/dL [3.0 mmol/L]) During the Controlled Fasting Challenge (CFC)	Baseline, Weeks 36 and 48	The LS mean and SE are based on MMRM analysis.
Japan Cohort: Change From Baseline to Week 48 in Time to Hypoglycemia (< 54 mg/dL [3.0 mmol/L]) During the CFC	Baseline, Weeks 36 and 48	—
Main Study: 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)	Baseline, Weeks 24, 30, 36, 42 and 48	The LS mean and SE are based on MMRM analysis.
Japan Cohort: 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)	Baseline, Weeks 24, 30, 36, 42 and 48	—
Main Study: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), Serious TEAEs, Related TEAEs, Fatal AEs, and Discontinuation From Study or Investigational Product Due to AEs	PEAP Arms - TEAEs with onset from Day 1 to Week 48; Crossover and Follow-up - Placebo to DTX401 Arm: TEAEs with onset after Week 48 dosing with DTX401 to Week 144; Crossover and Follow-up DTX401 Arm: TEAEs from Week 48 to Week 144	Adverse event (AE) is defined as any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related. TEAE is defined as any AE not present prior to initiation of drug treatment or any AE already present that worsens in either intensity or frequency following exposure to drug treatment. SAE is an AE that meets any of following criteria in view of either Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/incapacity; congenital anomaly/birth defect not present at screening; other important medical events. AESIs are events of scientific or medical interest specific to drug treatment requiring further investigation and close monitoring to further characterize them. Hepatic reactions (vector-induced hepatic effects) were AESIs for this study and were defined as clinically significant increases in aminotransferase levels (AST/ALT) in the judgment of Investigator.
Japan Cohort: Number of Participants With TEAEs, AESIs, Serious TEAEs, Related TEAEs, Fatal AEs, and Discontinuation From Study or Investigational Product Due to AEs	Day 1 to Week 48	AE is defined as any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related. TEAE is defined as any AE not present prior to initiation of drug treatment or any AE already present that worsens in either intensity or frequency following exposure to drug treatment. SAE is an AE that meets any of following criteria in view of either Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/incapacity; congenital anomaly/birth defect not present at screening; other important medical events. AESIs are events of scientific or medical interest specific to drug treatment requiring further investigation and close monitoring to further characterize them. Hepatic reactions were considered to be important identified risk for this study and were defined as clinically significant increases in aminotransferase levels (AST/ALT) in the judgment of Investigator.

Countries

Brazil, Canada, Denmark, Germany, Italy, Japan, Netherlands, Spain, United States

Contacts

STUDY_DIRECTORMedical Director

Ultragenyx Pharmaceutical Inc

Participant flow

Pre-assignment details

A total of 52 participants were enrolled in the study, including 49 in the main study and 3 in the Japan cohort. Three participants enrolled in the main study were randomized but not dosed.

Baseline characteristics

Characteristic	—
Age, Categorical <=18 years	23 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	26 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	3 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	41 Participants
Sex: Female, Male Female	19 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 21	0 / 19	0 / 21	0 / 3
other Total, other adverse events	23 / 25	20 / 21	19 / 19	20 / 21	3 / 3
serious Total, serious adverse events	3 / 25	8 / 21	10 / 19	9 / 21	0 / 3

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Oct 15, 2026