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

Browse trials for

• Glycogen Storage Disease 95

Keywords

• glycogen storage disorder Ia
• AAV
• gene therapy
• von Gierke disease
• glucose metabolism disorder

Glycogen Storage Disease

95 studies on the registry are indexed under Glycogen Storage Disease; 15 are open to participants now.

This study's enrollment of 12 is close to the median of 13 across 59 interventional studies indexed under Glycogen Storage Disease.

Lead sponsor

Ultragenyx Pharmaceutical Inc is the lead sponsor of 63 studies on the registry; 8 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 11 (85%) have results posted.

Eligibility criteria

Study arms

• Experimental
  DTX401 Cohort 1

  Dose 1 (2.0 × 10\^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after alanine aminotransferase \[ALT\] elevation)

  Genetic: DTX401 · Drug: steroid regimen

• Experimental
  DTX401 Cohort 2

  Dose 2 (6.0 × 10\^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after ALT elevation)

  Genetic: DTX401 · Drug: steroid regimen

• Experimental
  DTX401 Cohort 3

  Dose 2 (6.0 × 10\^12 GC/kg) with an optimized reactive steroid regimen (7 weeks, at a starting dose of 60 mg/day, after ALT elevation)

  Genetic: DTX401 · Drug: steroid regimen

• Experimental
  DTX401 Cohort 4

  Dose 2 (6.0 × 10\^12 GC/kg) with a prophylactic steroid regimen (8 weeks, at a starting dose of 60 mg/day, starting on Day 1)

  Genetic: DTX401 · Drug: steroid regimen

Interventions

• GeneticDTX401

  DTX401 administered as a single peripheral intravenous (IV) infusion

  Also known as: AAV8G6PC, Pariglasgene brecaparvovec

• Drugsteroid regimen

  prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation

Primary outcomes

1. 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

1. 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

Baseline characteristics

Publications

• Zhang L, Lee C, Arnaoutova I, Anduaga J, Starost MF, Mansfield BC, Chou JY. Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia. Biochem Biophys Res Commun. 2020 Jun 30;527(3):824-830. doi: 10.1016/j.bbrc.2020.04.124. Epub 2020 May 16. PubMed 32430177 ↗
• Zhang L, Cho JH, Arnaoutova I, Mansfield BC, Chou JY. An evolutionary approach to optimizing glucose-6-phosphatase-alpha enzymatic activity for gene therapy of glycogen storage disease type Ia. J Inherit Metab Dis. 2019 May;42(3):470-479. doi: 10.1002/jimd.12069. Epub 2019 Feb 22. PubMed 30714174 ↗

Study documents

• Study protocol · Feb 16, 2021
• Statistical analysis plan · Mar 4, 2022

Documents are hosted by the registry — open the source record to download them.