A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase (G6Pase) in Adults with Glycogen Storage Disease Type Ia (GSDIa)
- Conditions
- GSDIVon Gierke disease10027664
- Registration Number
- NL-OMON48684
- Lead Sponsor
- ltragenyx Pharmaceutical, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 1
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 (Section 9.2.1).
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>The incidence of adverse events (AEs), including the incidence of DLTs at<br /><br>each dose level, treatment-emergent adverse events (TEAEs), and serious<br /><br>adverse events (SAEs) for each dosing cohort, assessed by severity and<br /><br>relationship to study product.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>The change from baseline in time (in minutes) to first hypoglycemic event<br /><br>(defined as glucose <60 mg/dL [<3.33 mmol/L]) during a controlled fasting<br /><br>challenge at 6, 12, 24, and 52 weeks after IV administration of DTX401.</p><br>