Glycogen Storage Disease Type Ia (GSDIa). MedDRA version: 20.1 Level: LLT Classification code 10056911 Term: Glycogen storage disease type IA System Organ Class: 100000004850
Conditions
Sponsors
Ultragenyx Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
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. 8. Human immunodeficiency virus infection AND any of the following: CD4+ cell count 200 copies/mL on 2 separate occasions as measured by polymerase chain reaction. 9. Presence or history of any disease or condition that, in the Investigator’s opinion, would interfere with the subject’s safety or ability to participate in the study or would significantly affect interpretation of study results. This includes any intercurrent febrile or nonfebrile illness including common viral infections, epidemic influenza, and coronavirus disease 2019 (COVID-19) until full clinical recovery. 10. Female subjects of childbearing potential who have a positive serum pregnancy test at screening or a positive urine pregnancy test at baseline or who are unwilling to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, are postmenopausal (defined as having no menses for at least 12 months without an alternative medical cause), or are permanently sterile due to having total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. 11. Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study. 12. Presence or history of any hypersensitivity to the excipients of DTX401 or placebo or to prednisolone, or inability to swallow capsules that, in the judgment of the Investigator, places the subject at increased risk for adverse effects. 13. Current or previous participation in another gene transfer study. 14. Use of any IP or investigational medical device within 3 months preceding screening or planning to use at any time during the study. 15. History of illicit drug use within 60 days prior to screening or positive results from a 9-panel urine drug screen during the Screening Period completed at 2 time points at least 4 weeks apart. Positive results that are due to a prescribed medication may be allowed if not impacting glycemic control and liver function and after agreement with the Sponsor. For the purposes of this protocol, the use of recreational cannabis products is not allowed, even if legal in the region where the pati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To reduce or eliminate dependence on exogenous glucose replacement therapy to maintain euglycemia •To maintain or improve the quality of glucose control;Secondary Objective: •To evaluate the effect of DTX401 on glucose control •To evaluate the effect of DTX401 on reducing the frequency of exogenous glucose replacement therapy •To evaluate the effect of DTX401 on subject experience of disease •To evaluate the safety of DTX401;Primary end point(s): 1. Percent change from Baseline to Week 48 in daily cornstarch intake for the DTX401 Group compared with the Placebo Group for superiority. 2. Change from Baseline to Week 48 in the percentage of time spent in normal glucose control (60 to 120 mg/dL [3.3 to 6.7 mmol/L]) for the DTX401 Group compared with the Placebo Group, as measured by CGM for noninferiority.;Timepoint(s) of evaluation of this end point: 1. Baseline, week 12, week 24, week 30, week 36, week 42, week 48. 2. Baseline, day 1 to 12, week 12, week 24, week 30, week 36, week 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from Baseline to Week 48 in time to hypoglycemia (< 54 mg/dL [3.0 mmol/L]) during a CFC 2. Change from Baseline to Week 48 in percentage of time spent in normal glucose control (60 to 120 mg/dL [3.3 to 6.7 mmol/L]), as measured by CGM for superiority. 3. Change from Baseline to Week 48 in number of total daily doses of cornstarch. 4. Change from Baseline to Week 48 in the GSD FAD Signs and Symptoms Scale for the DTX401 Group compared with the Placebo Group. 5. Incidence, severity, and relationship to investigational product of TEAEs, TEAEs of special interest, serious TEAEs, related TEAEs, discontinuations from study or investigational product due to AEs, and fatal AEs. 6. Clinically relevant changes in standard chemistry, hematology, urinalysis panels, physical exams, and vital signs.;Timepoint(s) of evaluation of this end point: 1. Baseline, week 12, week 24, week 36, week 48. 2. Baseline, day 1 to 12, week 12, week 24, week 30, week 36, week 48. 3. Baseline, week 12, week 24, week 30, week 36, week 42, week 48. 4. Baseline, week 12, week 24, week 30, week 36, week 42, week 48. 5. From the time the subject signs the Informed Consent Form (ICF) and up to 30 days after the End of Study Visit or Early Withdrawal/Termination Visit. 6. From the time the subject signs the ICF and up to 30 days after the End of Study Visit or Early Withdrawal/Termination Visit | — |
Countries
Brazil, Canada, Denmark, France, Germany, Italy, Japan, Netherlands, Portugal, Spain, United States
Contacts
Public ContactClinical Development
Ultragenyx Pharmaceutical Inc.
Outcome results
None listed