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Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency (CAPtivate)

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ClinicalTrials.gov Identifier: NCT02991144
Recruitment Status : Active, not recruiting
First Posted : December 13, 2016
Last Update Posted : August 16, 2021
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Tracking Information
First Submitted Date  ICMJE December 9, 2016
First Posted Date  ICMJE December 13, 2016
Last Update Posted Date August 16, 2021
Study Start Date  ICMJE January 2017
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2016)
The incidence of treatment-related adverse events by dosing group [ Time Frame: 52 weeks ]
The incidence of adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) for each dosing cohort, assessed by severity and relationship to study product.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2020)
  • Change in baseline in ureagenesis rate [ Time Frame: 52 weeks ]
    The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea) as determined over time to 52 weeks after the IV administration of DTX301. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
  • Change in baseline 24 hour area under the curve of ammonia [ Time Frame: 52 weeks ]
    The change from baseline (Day 0) in area under the curve from time zero to 24 hours (AUC0 24) for serum ammonia over time to 52 weeks after IV administration of DTX301
Original Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2016)
  • Change in baseline in ureagenesis rate [ Time Frame: 52 weeks ]
    The change from baseline in the rate of ureagenesis (as measured by the generation of [13C]urea) as determined over time to 52 weeks after the IV administration of DTX301.
  • Change in baseline 24 hour area under the curve of ammonia [ Time Frame: 52 weeks ]
    The change from baseline (Day 0) in area under the curve from time zero to 24 hours (AUC0 24) for serum ammonia over time to 52 weeks after IV administration of DTX301
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency
Official Title  ICMJE A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency
Brief Summary A Phase 1/2, open-label dose-finding safety study of single ascending doses of DTX301 in adults with late-onset OTC Deficiency
Detailed Description

This is a Phase 1/2, open-label, single arm, multicenter, safety and dose finding study of DTX301 in adults with late-onset OTC deficiency. The primary objective of the study is to determine the safety of single IV doses of DTX301.

Eligible subjects will receive a single IV infusion of DTX301. Dose escalation will be conducted according to a model that uses the collected data to predict the safety profile of the dose in order to determine the optimal biological dose (OBD). The decision to proceed to the next dose cohort will be made after the data monitoring committee (DMC) has evaluated the safety data for all subjects in a dosing cohort.

Subjects will be followed for 52 weeks after dosing. After completion of this study, subjects will be asked to enroll in a 4-year extension study to evaluate the long term (a total of 5 years) safety and efficacy of DTX301.

This study was previously posted by Dimension Therapeutics, which has been acquired by Ultragenyx.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ornithine Transcarbamylase (OTC) Deficiency
Intervention  ICMJE
  • Genetic: scAAV8OTC
    non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
    Other Name: DTX301
  • Drug: Oral prednisone
    Initiated before dosing with DTX301, sustained for 4 weeks, followed by tapering
    Other Name: Oral prednisolone
Study Arms  ICMJE
  • Experimental: Dose 1: 2.0 × 10^12 GC/kg
    DTX301 (scAAV8OTC) will be administered as a single peripheral IV infusion. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
    Intervention: Genetic: scAAV8OTC
  • Experimental: Dose 2: 6.0 × 10^12 GC/kg
    DTX301 (scAAV8OTC) will be administered as a single peripheral IV infusion. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
    Intervention: Genetic: scAAV8OTC
  • Experimental: Dose 3: 1.0 × 10^13 GC/kg
    DTX301 (scAAV8OTC) will be administered as a single peripheral IV infusion. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
    Intervention: Genetic: scAAV8OTC
  • Experimental: Dosing Process Optimization at Optical Biological Dose (OBD)
    Oral prednisone (or prednisolone), 60 mg tapered over 9 weeks, initiated before dosing with DTX301. DTX301 (scAAV8OTC; optimal biologic dose) will be administered as a single peripheral IV infusion. Sodium acetate is used as a tracer to measure the rate of ureagenesis.
    Interventions:
    • Genetic: scAAV8OTC
    • Drug: Oral prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 16, 2021)
11
Original Estimated Enrollment  ICMJE
 (submitted: December 12, 2016)
9
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Males and females ≥18 years of age with documented diagnosis of late onset (defined as first manifestation of signs and symptoms at ≥1 month of age) OTC deficiency, confirmed via enzymatic, biochemical, or molecular testing
  2. Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L.
  3. Subject's OTC deficiency is stable as evidenced by either a) no clinical symptoms of hyperammonemia OR b) an ammonia level <100 µmol/L within the 4 week period preceding the Screening visit.
  4. On ongoing daily stable dose of ammonia scavenger therapy for ≥4 weeks.
  5. Males and all females of childbearing potential must be willing to use effective contraception at the time of administration of gene transfer and for the 52 weeks following administration of DTX301

Key Exclusion Criteria:

  1. At Screening or Baseline (Day 0), plasma ammonia level ≥ 100 μmol/L for patients who historically maintain normal ammonia levels; OR plasma ammonia level ≥ 200 μmol/L for patients who historically are not able to fully control ammonia levels with baseline management; OR signs and symptoms of hyperammonemia.
  2. Liver transplant, including hepatocyte cell therapy/transplant.
  3. History of liver disease
  4. Significant hepatic inflammation or cirrhosis
  5. Serum creatinine >2.0 mg/dL.
  6. Participation in another investigational medicine study (including another gene transfer trial) within 3 months of Screening
  7. Pregnant or nursing

Note additional inclusion/exclusion criteria may apply, per protocol.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02991144
Other Study ID Numbers  ICMJE 301OTC01
2016-001057-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ultragenyx Pharmaceutical Inc
Study Sponsor  ICMJE Ultragenyx Pharmaceutical Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Ultragenyx Pharmaceutical Inc
PRS Account Ultragenyx Pharmaceutical Inc
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP