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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05139316
Other study ID # DTX401-CL301
Secondary ID 2020-004184-12
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date November 8, 2021
Est. completion date February 2026

Study information

Verified date March 2024
Source Ultragenyx Pharmaceutical Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objectives of this study are to evaluate the efficacy of DTX401 to reduce or eliminate dependence on exogenous glucose replacement therapy to maintain euglycemia and to maintain or improve the quality of glucose control.


Description:

Study DTX401-CL301 is a phase 3 study to determine the efficacy and confirm the safety of DTX401 in patients 8 years and older with glycogen storage disease type Ia (GSDIa). Participants will be randomized 1:1 to DTX401 or placebo group, and followed closely for 48 weeks. At week 48 eligible participants will cross over and receive DTX401 if they had previously received placebo or placebo if they had previously received DTX401, and will be followed closely for an additional 96 weeks. After completion of week 144 or early withdrawal, participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion. In Japan, there will be a single open label study arm and all participants will be treated with DTX401. At week 48, Japanese participants will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post DTX401 infusion.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 46
Est. completion date February 2026
Est. primary completion date February 20, 2024
Accepts healthy volunteers No
Gender All
Age group 8 Years and older
Eligibility Key Inclusion Criteria: - Documented GSDIa with confirmation by molecular testing or enzymatic activity on liver biopsy - Currently receiving a therapeutic regimen of cornstarch (or equivalent), following international guidance/recommendations with stable nutrition, glycemic, and clinical status. - Willing and able to complete the informed consent process and to comply with study procedures and visit schedule - Females of childbearing potential and fertile males must consent to use highly effective contraception from the period following informed consent through the duration of the 144-week study and in cases of early withdrawal at least 48 weeks after the last dose of investigational product (IP). Female subjects must agree not to become pregnant. Male subjects must agree not to father a child or donate sperm Key Exclusion Criteria: - Detectable pre-existing antibodies to the AAV8 capsid - History of liver transplant, including hepatocyte cell therapy/ transplant - History of liver disease - Presence of liver adenoma >5 cm in size - Presence of liver adenoma >3 cm and =5 cm in size that has a documented annual growth rate of =0.5 cm per year - Significant hepatic inflammation or cirrhosis as evidenced by imaging or any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN), total bilirubin >1.5 × ULN, alkaline phosphatase >2.5 × ULN - Non-fasting triglycerides =1000 mg/dL - Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study. - Current or previous participation in another gene transfer study - History of illicit drug use within 60 days prior to screening or positive results from an 8-panel urine drug screen during the Screening Period completed at 2 time points at least 4 weeks apart Note: additional inclusion/exclusion criteria may apply, per protocol

Study Design


Intervention

Genetic:
DTX401
nonreplicating, recombinant, adeno-associated virus (AAV) serotype 8 (AAV8)
Other:
Placebo
Normal Saline infusion
Drug:
Oral corticosteroids
Participants who receive DTX401 solution will receive oral corticosteroids
Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo oral corticosteroids to maintain the study blind

Locations

Country Name City State
Brazil Hospital de Clinicas de Porto Alegre Porto Alegre Rio Grande Do Sul
Canada McGill University Montréal Quebec
Denmark Righospitalet Kopenhagen Capital
Germany University Medical Center Eppendorf Hamburg
Italy Istituto Giannina Gaslini Genova Linguria
Italy University of Naples Naples
Netherlands Groningen University Groningen
Spain Hospital Clinico Universitario de Santiago Santiago De Compostela A Coruna
United States Children's Hospital Colorado Aurora Colorado
United States Mount Sinai Bronx New York
United States Cleveland Clinic Cleveland Ohio
United States Duke University Durham North Carolina
United States University of Connecticut Health Center Farmington Connecticut
United States University of Texas Houston Texas
United States Children's Hospital of Orange County Orange California
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Primary Children's Hospital Salt Lake City Utah

Sponsors (1)

Lead Sponsor Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Denmark,  Germany,  Italy,  Netherlands,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percent Change from Baseline to Week 48 in Daily Cornstarch Intake Baseline, Week 48
Secondary Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch in DTX401 Group Compared to Placebo Group Baseline, Week 48
Secondary Change from Baseline to Week 48 in Percentage of Glucose Values in Hypoglycemic Range (<70mg/dL [3.9 mmol/L]) Baseline, Week 48
Secondary Patient Global Impression of Change (PGIC) Assessment Score at Week 48 Baseline, Week 48
Secondary Change from Baseline to Week 48 in Time to Hypoglycemia (<54 mg/dL [3.0 mmol/L]) During a Controlled Fasting Challenge Baseline, Week 48
Secondary Change from Baseline to Week 48 in Percentage of Glucose Values in the Range of 70-120 mg/dL (3.9-6.7 mmol/L) Baseline, Week 48
Secondary Number of Treatment Emergent Adverse Events (TEAEs), TEAEs of Special Interest, Serious TEAEs, Related TEAEs, Discontinuations From Study or Investigational Product Due to Adverse Events (AEs), and Fatal AEs up to 144 weeks
See also
  Status Clinical Trial Phase
Completed NCT04708015 - Retrospective Study of Glucose Monitoring for Glycemic Control in Patients With GSDIa
Completed NCT01854242 - Study of the Relationship Between Glycogen Storage Disease Type Ia and Inflammatory Bowel Disease
Completed NCT02054832 - Sleep and Quality of Life in Patients With Glycogen Storage Disease on Standard Versus Modified Uncooked Cornstarch N/A
Terminated NCT04909346 - Adeno-Associated Virus (AAV) Antibody Study in Subjects OTC Deficiency, GSDIa, and Wilson Disease
Active, not recruiting NCT03970278 - Study of Long-Term Safety and Efficacy on Gene Therapy in Glycogen Storage Disease Type Ia
Completed NCT04311307 - Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia Phase 1/Phase 2