Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients With Glycogen Storage Disease Type Ia (GSDIa)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05139316
Recruitment Status : Recruiting
First Posted : December 1, 2021
Last Update Posted : June 10, 2022
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief 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.

Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type IA Genetic: DTX401 Other: Placebo Drug: Oral corticosteroids Drug: Placebo for oral corticosteroids Phase 3

Detailed Description:
Study DTX401-CL301 is a phase 3, randomized, double-blind, placebo-controlled 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 48 weeks. After completion of week 96 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 8, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2024


Arm Intervention/treatment
Experimental: DTX401, Then Placebo
Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.
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
Other Name: prednisolone

Drug: Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo oral corticosteroids to maintain the study blind

Placebo Comparator: Placebo, Then DTX401
Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.
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
Other Name: prednisolone

Drug: Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo oral corticosteroids to maintain the study blind




Primary Outcome Measures :
  1. Percent Change from Baseline to Week 48 in Daily Cornstarch Intake [ Time Frame: Baseline, Week 48 ]
  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]) as Measured by Continuous Glucose Monitoring (CGM) for Noninferiority [ Time Frame: Baseline, Week 48 ]

Secondary Outcome Measures :
  1. Change from Baseline to Week 48 in Time to Hypoglycemia (< 54 mg/dL [< 3.0 mmol/L]) During a Controlled Fasting Challenge [ Time Frame: Baseline, Week 48 ]
  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 [ Time Frame: Baseline, Week 48 ]
  3. Change from Baseline to Week 48 in Number of Total Daily Doses of Cornstarch [ Time Frame: Baseline, Week 48 ]
  4. Change from Baseline to Week 48 in the Glycogen Storage Disease Functional Assessment Diary (GSD FAD) Signs and Symptoms Scale [ Time Frame: Baseline, Week 48 ]
  5. 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 [ Time Frame: up to 96 weeks ]
  6. Number of Participants with Clinically Relevant Changes in Standard Chemistry [ Time Frame: up to 96 weeks ]
  7. Number of Participants with Clinically Relevant Changes in Hematology [ Time Frame: up to 96 weeks ]
  8. Number of Participants with Clinically Relevant Changes in Urinalysis [ Time Frame: up to 96 weeks ]
  9. Number of Participants with Clinically Relevant Changes in Physical Exams [ Time Frame: up to 96 weeks ]
  10. Number of Participants with Clinically Relevant Changes in Vital Signs [ Time Frame: up to 96 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) and is clinically stable as evidenced by no more than a 10% change in cornstarch (or equivalent) regimen and no hospitalization for hypoglycemia over a 4 week period
  • 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 96-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 6 weeks apart

Note additional inclusion/exclusion criteria may apply, per protocol


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05139316


Contacts
Layout table for location contacts
Contact: Patients Contact: Trial Recruitment 1-888-756-8657 TrialRecruitment@ultragenyx.com
Contact: HCPs Contact: Medical Information 1-888-756-8657 medinfo@ultragenyx.com

Locations
Show Show 29 study locations
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
Layout table for investigator information
Study Director: Medical Director Ultragenyx Pharmaceutical Inc
Additional Information:
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT05139316    
Other Study ID Numbers: DTX401-CL301
2020-004184-12 ( EudraCT Number )
First Posted: December 1, 2021    Key Record Dates
Last Update Posted: June 10, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ultragenyx Pharmaceutical Inc:
glycogen storage disorder Ia
AAV
gene therapy
von Gierke disease
glucose metabolism disorder
GSDIa
GSD1
Additional relevant MeSH terms:
Layout table for MeSH terms
Glycogen Storage Disease
Glycogen Storage Disease Type I
Metabolic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Prednisolone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents