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.EMA Decision number on PIP: EMA/PDCO/154270/2021

ltragenyx Pharmaceutical Inc.0 sites50 target enrollmentSeptember 29, 2021

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: ltragenyx Pharmaceutical Inc.
Enrollment: 50
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

September 29, 2021

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

ltragenyx Pharmaceutical Inc.

Eligibility Criteria

Inclusion Criteria

•1\. Male and female patients \= 8 years of age at time of informed consent or assent.
•2\. Subject has a diagnosis of GSDIa confirmed by deficient enzymatic activity (on liver biopsy), or by molecular testing of G6PC gene revealing 2 pathogenic mutations. In the case where only a single pathogenic mutation is identified, clinical diagnosis is compatible with GSDIa and absence of characteristic features of GSDIb (ie, chronic neutropenia, inflammatory bowel disease).
•3\. Subject is currently receiving a therapeutic regimen of cornstarch (or equivalent) and clinically stable as evidenced by no more than a 10% weekly change in cornstarch (or equivalent) regimen; no more than 15% variation in weekly average euglycemia (60\-120 mg/dL) assessed by CGM and no hospitalization for hypoglycemia during the 4\-week period preceding randomization and dosing.
•4\. Subject is willing and able to comply with study procedures and requirements, including periodic inpatient hospitalization or admission in a research facility; CFC studies; frequent blood collection; wearing a CGM device for the duration of the study (and excluding the use of any non\-study CGM or flash glucose device); performing capillary glucose measurements using a study\-approved glucometer (and excluding the use of any other glucometer); completing an eDiary routinely throughout the study to track daily cornstarch, dietary intake, and reason for performing SMBG; and completing patient\-reported questionnaires. If \< 18 years (or as required by region), has a parent or legal guardian willing and able to assist with study requirements.
•5\. From the period following informed consent through the duration of participation in the study, female subjects of childbearing potential and fertile male subjects must consent to use highly effective contraception as defined by the Food and Drug Administration (FDA) and Clinical Trial Facilitation Group Recommendations Related to Contraception and Pregnancy Testing in Clinical Trials (Version 1\.1 dated 21 Sep 2020\). Female subjects must agree not to become pregnant and male subjects must agree not father a child or donate sperm for at least 48 weeks after the last dose of IP if they decide to withdraw early from the study.
•6\. Subject is willing and able to provide written informed consent after the study has been explained and before any study\-related procedures are performed. If \< 18 years (or as required by region), willing and able to provide written assent and have a parent or legal guardian willing and able to provide written informed consent after the study has been explained and before any study\-related procedures are performed.
•Are the trial subjects under 18? yes
•Number of subjects for this age range: 10
•F.1\.2 Adults (18\-64 years) yes
•F.1\.2\.1 Number of subjects for this age range 36

Exclusion Criteria

•1\. Detectable pre\-existing antibodies to the AAV8 capsid.
•2\. History of liver transplant, including hepatocyte cell therapy/transplant.
•3\. History of liver disease as evidenced by any of the following: portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, or a liver biopsy with evidence of stage III fibrosis.
•4\. Presence of liver adenoma \> 5 cm in size or presence of liver adenoma \> 3 cm and \= 5 cm in size with 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:
•\- ALT or aspartate aminotransferase \> 2\.5 × the ULN
•\- Total bilirubin \> 2\.0 × ULN (except if patient has documented Gilbert’s syndrome)
•\- Alkaline phosphatase \> 2\.5 × ULN
•6\.Non\-fasting triglycerides \= 1000 mg/dL. For the purposes of this study, non\-fasting refers to the longest fasting period that each individual subject is able to tolerate. Depending on the meal and cornstarch schedule, the blood draw could occur in the morning before breakfast or before the first dose of cornstarch.
•7\. Presence or history of hepatitis B virus infection, hepatitis C virus infection, or both.