Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa)

Ultragenyx Pharmaceutical Inc12 enrolled

Overview

The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level.

Participants enrolled in the 401GSDIA01 study will be monitored for 52 weeks following DTX401 administration. Participants in Cohorts 1, 2, and 3 will receive reactive oral steroid treatment for possible vector-induced hepatitis following treatment with DTX401. Participants in Cohort 4 will receive prophylactic oral steroid treatment to prevent possible vector-induced hepatitis. After completion of the Week 52 visit or early withdrawal, participants will be offered enrollment into a 4-year extension study.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

GSD1

Interventions

DTX401GENETIC

DTX401 administered as a single peripheral intravenous (IV) infusion

steroid regimenDRUG

prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Males and females ≥18 years of age * Documented GSDIa with confirmation by molecular testing * Documented history of ≥1 hypoglycemic event with blood glucose \<60 mg/dL (\<3.33 mmol/L) * Patient's GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit Key Exclusion Criteria: * Anti-AAV8 neutralizing antibody titer ≥1:5 * Screening or Baseline (Day 0) blood glucose level \<60 mg/dL (\<3.33 mmol/L) * Liver transplant, including hepatocyte cell therapy/transplant * 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 x ULN, or alkaline phosphatase \> 2.5 x ULN Note additional inclusion/exclusion criteria may apply, per protocol.

Locations (6)

UCONN Health

Farmington, Connecticut, United States

Michigan Medicine University of Michigan

Ann Arbor, Michigan, United States

UT Health - McGovern Medical School

Houston, Texas, United States

Montreal Children Hospital, McGill University Health Centre

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs)

An AE is defined as any untoward medical occurrence, regardless of its causal relationship to study product. An SAE is defined as any event that: results in death; is immediately life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; or an important medical event, in the opinion of the investigator. The relationship to study drug was categorized as unrelated, possible, probable or definite. A DLT is defined as any AE/SAE ≥ Grade 3 that is considered by the Investigator and/or Sponsor to be related to DTX401, based on the Nation Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 or later version. Per protocol, SAEs that occurred \> 30 days after EOS or Early withdrawal visit, did not need to be reported unless Investigator considered them related to study product.

Time frame: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug through the End of Study (EOS)/Early Withdrawal visit (up to Week 52) plus 30 days.

Secondary Outcomes

Change From Baseline in Time to First Hypoglycemic Event Over Time

The change from baseline in time (in hours) to first hypoglycemic event (defined as glucose \< 54 mg/dL \[\< 3.0 mmol/L\]) during a controlled fasting challenge at 12, 24, and 52 weeks after IV administration of DTX401. A positive change from baseline is favorable.

Time frame: Baseline, Weeks 12, 24, 52

Data from ClinicalTrials.gov

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