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 :
Completed
First Posted : December 13, 2016
Last Update Posted : January 5, 2022
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Condition or disease | Intervention/treatment | Phase |
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Ornithine Transcarbamylase (OTC) Deficiency | Genetic: scAAV8OTC Drug: Oral prednisone | Phase 1 Phase 2 |
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 : | Interventional (Clinical Trial) |
Actual Enrollment : | 11 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency |
Study Start Date : | January 2017 |
Actual Primary Completion Date : | December 15, 2021 |
Actual Study Completion Date : | December 15, 2021 |

Arm | Intervention/treatment |
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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.
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Genetic: scAAV8OTC
non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
Other Name: DTX301 |
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.
|
Genetic: scAAV8OTC
non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
Other Name: DTX301 |
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.
|
Genetic: scAAV8OTC
non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC)
Other Name: DTX301 |
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.
|
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 |
- 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.
- 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

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- 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
- Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L.
- 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.
- On ongoing daily stable dose of ammonia scavenger therapy for ≥4 weeks.
- 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:
- 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.
- Liver transplant, including hepatocyte cell therapy/transplant.
- History of liver disease
- Significant hepatic inflammation or cirrhosis
- Serum creatinine >2.0 mg/dL.
- Participation in another investigational medicine study (including another gene transfer trial) within 3 months of Screening
- Pregnant or nursing
Note additional inclusion/exclusion criteria may apply, per protocol.

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): NCT02991144
United States, Colorado | |
The Children's Hospital Colorado | |
Aurora, Colorado, United States, 80045 | |
United States, Massachusetts | |
Boston Children's Hospital | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Icahn School of Medicine at Mount Sinai | |
New York, New York, United States, 10029-6508 | |
United States, Ohio | |
University Hospital Cleveland Medical Center/Case Western Reserve University | |
Cleveland, Ohio, United States, 44106 | |
Canada, Alberta | |
Alberta's Children's Hospital | |
Calgary, Alberta, Canada, T3B 6A8 | |
Spain | |
Hospital Clinico Universitario de Santiago | |
Santiago de Compostela, A Coruna, Spain, 15706 | |
Hospital Universitario de Cruzes | |
Barakaldo, Vizcaya, Spain, 48903 | |
United Kingdom | |
National Hospital for Neurology & Neurosurgery | |
London, London City, United Kingdom, WC1N 3BG | |
Queen Elizabeth Hospital | |
Birmingham, United Kingdom, B15 2TH |
Study Director: | Medical Director | Ultragenyx Pharmaceutical Inc |
Responsible Party: | Ultragenyx Pharmaceutical Inc |
ClinicalTrials.gov Identifier: | NCT02991144 |
Other Study ID Numbers: |
301OTC01 2016-001057-40 ( EudraCT Number ) |
First Posted: | December 13, 2016 Key Record Dates |
Last Update Posted: | January 5, 2022 |
Last Verified: | January 2022 |
Gene Transfer OTC Deficiency Urea Cycle Disorder |
Ornithine Carbamoyltransferase Deficiency Disease Urea Cycle Disorders, Inborn Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Genetic Diseases, X-Linked Genetic Diseases, Inborn Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors |
Metabolic Diseases Prednisone Prednisolone Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents |