Clinical trial NCT05139316: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Glycogen Storage Disease Type IA
Keywords: glycogen storage disorder Ia
AAV
gene therapy
von Gierke disease
glucose metabolism disorder
GSDIa
GSD1
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2021-12-01
Enrollment: 49
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 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.

In Japan, there will be a single open label study arm and all participants will be treated with DTX401. At week 48, Japanese participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion.

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

Primary outcomes:
measure: Percent Change from Baseline to Week 48 in Daily Cornstarch Intake
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group
timeFrame: Baseline, Week 48
measure: Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L])
timeFrame: Baseline, Week 48
measure: Patient Global Impression of Change (PGIC) Assessment Score at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline to Week 48 in Time to Hypoglycemia (<54 mg/dL [3.0 mmol/L]) During a Controlled Fasting Challenge
timeFrame: Baseline, Week 48
measure: 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)
timeFrame: Baseline, Week 48
measure: 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
timeFrame: up to 144 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Bronx
country: United States
facility: Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Montréal
country: Canada
facility: McGill University
state: Quebec
city: Kopenhagen
country: Denmark
facility: Righospitalet
state: Capital
city: Hamburg
country: Germany
facility: University Medical Center Eppendorf
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
state: Linguria
city: Naples
country: Italy
facility: University of Naples
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Groningen
country: Netherlands
facility: Groningen University
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
state: A Coruna
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References: