GSD1Phase 1/2NCT03517085
Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa)
A Phase 1/2 study testing DTX401 and steroid regimen in people with GSD1, run by Ultragenyx Pharmaceutical Inc at 6 sites in 4 countries.
Trial summary
The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GSD1
- What is being tested?
- DTX401 and steroid regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 18 May 2018to 2 Nov 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females ≥18 years of age
- Documented GSDIa with confirmation by molecular testing
- Documented history of ≥1 hypoglycemic event with blood glucose <60 mg/dL (<3.33 mmol/L)
- Patient's GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit
Who cannot join
- Anti-AAV8 neutralizing antibody titer ≥1:5
- Screening or Baseline (Day 0) blood glucose level <60 mg/dL (<3.33 mmol/L)
- Liver transplant, including hepatocyte cell therapy/transplant
- 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 x ULN, or alkaline phosphatase > 2.5 x ULN
- Note additional inclusion/exclusion criteria may apply, per protocol.
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
Michigan Medicine University of Michigan
Ann Arbor, Michigan, 48109
UCONN Health
Farmington, Connecticut, 06030-3213
UT Health - McGovern Medical School
Houston, Texas, 77030
Canada1 site
Montreal Children Hospital, McGill University Health Centre
Montreal, Quebec, H4A3J1
Spain1 site
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, A Coruna, 15706
About this study
Official title: 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)
The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level.
Read the detailed description
Participants enrolled in the 401GSDIA01 study will be monitored for 52 weeks following DTX401 administration. Participants in Cohorts 1, 2, and 3 will receive reactive oral steroid treatment for possible vector-induced hepatitis following treatment with DTX401. Participants in Cohort 4 will receive prophylactic oral steroid treatment to prevent possible vector-induced hepatitis. After completion of the Week 52 visit or early withdrawal, participants will be offered enrollment into a 4-year extension study.
- Conditions
- GSD1
- Being tested
- DTX401, steroid regimen
- Keywords
- glycogen storage disorder Ia, AAV, gene therapy, von Gierke disease, glucose metabolism disorder
- Medical subject headings
- Glycogen Storage Disease Type I, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTX401Genetic
Also called AAV8G6PC, Pariglasgene brecaparvovec
DTX401 administered as a single peripheral intravenous (IV) infusion
steroid regimenDrug
prednisone or prednisolone to manage alanine aminotransferase (ALT) elevation
| Study group | Role | What they receive |
|---|---|---|
| DTX401 Cohort 1 | Experimental | Dose 1 (2.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after alanine aminotransferase [ALT] elevation) Receives: Genetic: DTX401; Drug: steroid regimen |
| DTX401 Cohort 2 | Experimental | Dose 2 (6.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after ALT elevation) Receives: Genetic: DTX401; Drug: steroid regimen |
| DTX401 Cohort 3 | Experimental | Dose 2 (6.0 × 10^12 GC/kg) with an optimized reactive steroid regimen (7 weeks, at a starting dose of 60 mg/day, after ALT elevation) Receives: Genetic: DTX401; Drug: steroid regimen |
| DTX401 Cohort 4 | Experimental | Dose 2 (6.0 × 10^12 GC/kg) with a prophylactic steroid regimen (8 weeks, at a starting dose of 60 mg/day, starting on Day 1) Receives: Genetic: DTX401; Drug: steroid regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs)
An AE is defined as any untoward medical occurrence, regardless of its causal relationship to study product. An SAE is defined as any event that: results in death; is immediately life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; or an important medical event, in the opinion of the investigator. The relationship to study drug was categorized as unrelated, possible, probable or definite. A DLT is defined as any AE/SAE ≥ Grade 3 that is considered by the Investigator and/or Sponsor to be related to DTX401, based on the Nation Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 or later version. Per protocol, SAEs that occurred > 30 days after EOS or Early withdrawal visit, did not need to be reported unless Investigator considered them related to study product.
Measured: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug through the End of Study (EOS)/Early Withdrawal visit (up to Week 52) plus 30 days.
Secondary outcomes (1)
Change From Baseline in Time to First Hypoglycemic Event Over Time
The change from baseline in time (in hours) to first hypoglycemic event (defined as glucose < 54 mg/dL [< 3.0 mmol/L]) during a controlled fasting challenge at 12, 24, and 52 weeks after IV administration of DTX401. A positive change from baseline is favorable.
Measured: Baseline, Weeks 12, 24, 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2018
- Study start18 May 2018
- Primary completion2 Nov 2021
- Study completion2 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for GSD1Studies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03517085
- Sponsor's protocol ID
- 401GSDIA01
- Other IDs
- 1706-1617, 2016-003023-30, 2016
- Status last verified
- Oct 2022
- First submitted
- 24 Apr 2018
- Last updated
- 18 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Weinstein DA, Derks TG, Rodriguez-Buritica DF, Ahmad A, Couce ML, Mitchell JJ, Riba-Wolman R, Mount M, Sallago JB, Ross KM, van der Klauw MM, de Boer F, van der Schaaf C, Saavedra H, Martinez-Olmos M, Atanga E, Hosseini A, Mitragotri D, Crombez E. Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa). J Inherit Metab Dis. 2025 Mar;48(2):e70014. doi: 10.1002/jimd.70014.
PubMed 40064185Zhang L, Lee C, Arnaoutova I, Anduaga J, Starost MF, Mansfield BC, Chou JY. Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia. Biochem Biophys Res Commun. 2020 Jun 30;527(3):824-830. doi: 10.1016/j.bbrc.2020.04.124. Epub 2020 May 16.
PubMed 32430177Zhang L, Cho JH, Arnaoutova I, Mansfield BC, Chou JY. An evolutionary approach to optimizing glucose-6-phosphatase-alpha enzymatic activity for gene therapy of glycogen storage disease type Ia. J Inherit Metab Dis. 2019 May;42(3):470-479. doi: 10.1002/jimd.12069. Epub 2019 Feb 22.
PubMed 30714174
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03517085
- Acronym / sponsor ID
- 401GSDIA01
- Conditions
- GSD1
- Keywords
- glycogen storage disorder Ia, AAV, gene therapy, von Gierke disease, glucose metabolism disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 18 May 2018 (actual)
- Primary completion
- 2 Nov 2021 (actual)
- Study completion
- 2 Nov 2021 (actual)
- First posted
- 7 May 2018 (actual)
- Results
- Posted 18 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to determine the safety of single doses of DTX401, including the incidence of dose-limiting toxicities (DLTs) at each dose level.
Detailed description
Participants enrolled in the 401GSDIA01 study will be monitored for 52 weeks following DTX401 administration. Participants in Cohorts 1, 2, and 3 will receive reactive oral steroid treatment for possible vector-induced hepatitis following treatment with DTX401. Participants in Cohort 4 will receive prophylactic oral steroid treatment to prevent possible vector-induced hepatitis. After completion of the Week 52 visit or early withdrawal, participants will be offered enrollment into a 4-year extension study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DTX401 Cohort 1 | Experimental | Genetic: DTX401, Drug: steroid regimenDose 1 (2.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after alanine aminotransferase [ALT] elevation) |
| DTX401 Cohort 2 | Experimental | Genetic: DTX401, Drug: steroid regimenDose 2 (6.0 × 10^12 GC/kg) with a reactive steroid regimen (6 weeks, at a starting dose of 40 mg/day, after ALT elevation) |
| DTX401 Cohort 3 | Experimental | Genetic: DTX401, Drug: steroid regimenDose 2 (6.0 × 10^12 GC/kg) with an optimized reactive steroid regimen (7 weeks, at a starting dose of 60 mg/day, after ALT elevation) |
| DTX401 Cohort 4 | Experimental | Genetic: DTX401, Drug: steroid regimenDose 2 (6.0 × 10^12 GC/kg) with a prophylactic steroid regimen (8 weeks, at a starting dose of 60 mg/day, starting on Day 1) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females ≥18 years of age
- Documented GSDIa with confirmation by molecular testing
- Documented history of ≥1 hypoglycemic event with blood glucose <60 mg/dL (<3.33 mmol/L)
- Patient's GSDIa disease is stable as evidenced by no hospitalization for severe hypoglycemia during the 4-week period preceding the screening visit
Key exclusion criteria (7 listed)
- Anti-AAV8 neutralizing antibody titer ≥1:5
- Screening or Baseline (Day 0) blood glucose level <60 mg/dL (<3.33 mmol/L)
- Liver transplant, including hepatocyte cell therapy/transplant
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DTX401Also: AAV8G6PC, Pariglasgene brecaparvovecDTX401 administered as a single peripheral intravenous (IV) infusion | Genetic | DTX401 Cohort 1, DTX401 Cohort 2, DTX401 Cohort 3, DTX401 Cohort 4 |
| steroid regimenprednisone or prednisolone to manage alanine aminotransferase (ALT) elevation | Drug | DTX401 Cohort 1, DTX401 Cohort 2, DTX401 Cohort 3, DTX401 Cohort 4 |
Primary outcome
Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs)
Time frame: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug through the End of Study (EOS)/Early Withdrawal visit (up to Week 52) plus 30 days.
An AE is defined as any untoward medical occurrence, regardless of its causal relationship to study product. An SAE is defined as any event that: results in death; is immediately life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; or an important medical event, in the opinion of the investigator. The relationship to study drug was categorized as unrelated, possible, probable or definite. A DLT is defined as any AE/SAE ≥ Grade 3 that is considered by the Investigator and/or Sponsor to be related to DTX401, based on the Nation Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 or later version. Per protocol, SAEs that occurred > 30 days after EOS or Early withdrawal visit, did not need to be reported unless Investigator considered them related to study product.
1 secondary outcome
Change From Baseline in Time to First Hypoglycemic Event Over Time
Time frame: Baseline, Weeks 12, 24, 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40064185Weinstein DA, Derks TG, Rodriguez-Buritica DF, Ahmad A, Couce ML, Mitchell JJ, Riba-Wolman R, Mount M, Sallago JB, Ross KM, van der Klauw MM, de Boer F, van der Schaaf C, Saavedra H, Martinez-Olmos M, Atanga E, Hosseini A, Mitragotri D, Crombez E. Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa). J Inherit Metab Dis. 2025 Mar;48(2):e70014. doi: 10.1002/jimd.70014.
- Derived from this study: PubMed 32430177Zhang L, Lee C, Arnaoutova I, Anduaga J, Starost MF, Mansfield BC, Chou JY. Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia. Biochem Biophys Res Commun. 2020 Jun 30;527(3):824-830. doi: 10.1016/j.bbrc.2020.04.124. Epub 2020 May 16.
- Derived from this study: PubMed 30714174Zhang L, Cho JH, Arnaoutova I, Mansfield BC, Chou JY. An evolutionary approach to optimizing glucose-6-phosphatase-alpha enzymatic activity for gene therapy of glycogen storage disease type Ia. J Inherit Metab Dis. 2019 May;42(3):470-479. doi: 10.1002/jimd.12069. Epub 2019 Feb 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DTX401 and steroid regimen in people with GSD1, run by Ultragenyx Pharmaceutical Inc at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) Treatment-Emergent AEs (TEAEs) Serious TEAEs, Discontinuations Due to TEAEs, and Dose-Limiting Toxicities (DLTs) (time frame: AEs Prior to Dosing: From signing the informed consent form (ICF) to first dose of study drug. TEAEs: From first dose of study drug through the End of Study (EOS)/Early Withdrawal visit (up to Week 52) plus 30 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03517085, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2022.