An early-phase clinical study of a vector transferring the gene for Glucose-6-Phosphatase (G6Pase) in adults with Glycogen Storage Disease Type Ia.
- Conditions
- Glycogen Storage Disease Type Ia (GSDIa).MedDRA version: 20.1Level: LLTClassification code 10056911Term: Glycogen storage disease type IASystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2016-003023-30-NL
- Lead Sponsor
- ltragenyx Pharmaceutical, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
1. Willing and able to provide written informed consent.
2. Males and females =18 years of age.
3. Documented GSDIa with confirmation by molecular testing.
4. Documented history of =1 hypoglycemic event with glucose <60 mg/dL (<3.33 mmol/L).
5. Subject’s GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit.
6. Hematology and coagulation panel results are within the normal range or, if outside the normal range, are deemed not clinically significant in the opinion of the investigator.
7. No known allergic reaction to any component of DTX401.
8. Willing and able to comply with study procedures and requirements, including periodic inpatient hospitalization, frequent blood collections, and 24-hour urine collection.
9. Males and females of childbearing potential must be willing to use effective contraception at the time of administration of DTX401 and for 52 weeks following administration of DTX401 to prevent the potential transmission of the AAV vector.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
1. Screening or Baseline (Day 0) glucose level <60 mg/dL (<3.33 mmol/L); subjects may be
rescreened after glucose is controlled and stable, at the discretion of the investigator.
2. Liver transplant, including hepatocyte cell therapy/transplant.
3. Presence of liver adenoma >5 cm in size.
4. Presence of liver adenoma >3 cm and =5 cm in size that has a documented annual growth rate of =0.5 cm per year.
5. Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase > the upper limit of normal (ULN), total bilirubin >1.5 × ULN, or alkaline phosphatase >2.5 × ULN. Liver function tests may be repeated during the screening period at the investigator’s discretion.
6. Serum creatinine >2.0 mg/dL.
7. Triglycerides =1000 mg/dL at the time of the screening visit.
8. Presence of active, or history of treatment for, hepatitis B virus or hepatitis C virus infection.
9. History of human immunodeficiency virus infection AND any of the following: CD4+ cell count <350 cells/mm3, change in antiretroviral therapy regimen within 6 months prior to
Day 0, or viral load >200 copies/mL, on 2 separate occasions, as measured by polymerase chain reaction.
10. History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer treated with watchful waiting or surgically removed nonmelanoma skin cancer.
11. Active infection (viral or bacterial).
12. Anti-AAV8 neutralizing antibody titer =1:5.
13. Participation (current or previous) in another gene transfer study.
14. Participation in another investigational product study within 3 months of Screening.
15. Has a positive serum pregnancy test at Screening (females of childbearing potential only), a positive urine pregnancy test at Baseline (Day 0; females of childbearing potential only), or is nursing.
16. Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the safety of single IV doses of DTX401 in adults with GSDIa, including the incidence of dose-limiting toxicities (DLTs).;Secondary Objective: To establish a dose of DTX401 that achieves symptom-free euglycemia (glucose =60 mg/dL<br>[=3.33 mmol/L]) in a setting of a controlled fasting challenge to allow further clinical development.;Primary end point(s): The incidence of AEs, including the incidence of DLTs at each dose level, TEAEs, and SAEs for each dosing cohort, assessed by severity and relationship to study product.;Timepoint(s) of evaluation of this end point: From the time the subject signs the Informed Consent Form (ICF) up to 30 days after the end of study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The change from baseline in time (in minutes) to first hypoglycemic event (defined as glucose <60 mg/dL [<3.33 mmol/L]) during a controlled fasting challenge at 6, 12, 24, and 52 weeks after IV administration of DTX401.;Timepoint(s) of evaluation of this end point: 6, 12, 24 and 54 weeks after IV administration of DTX401