Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency (CAPtivate)
|
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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02991144 |
|
Recruitment Status :
Active, not recruiting
First Posted : December 13, 2016
Last Update Posted : March 30, 2020
|
Sponsor:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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) |
| Estimated Enrollment : | 15 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 |
| Estimated Primary Completion Date : | February 2021 |
| Estimated Study Completion Date : | February 2021 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Ornithine transcarbamylase deficiency
Drug Information available for:
Prednisone
| Arm | Intervention/treatment |
|---|---|
|
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.
|
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
Oral prednisone (or prednisolone), 60 mg tapered to 5 mg over ≤ 9 weeks, will be 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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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 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
Exclusion Criteria:
- Screening or Baseline (Day 0) ammonia level ≥100 µmol/L or signs and symptoms indicative of hyperammonemia during the 4-week period preceding Day 0
- Liver transplant, including hepatocyte cell therapy/transplant.
- History of liver disease
- Serum creatinine >2.0 mg/dL.
- Participation in another investigational medicine study (including another gene transfer trial) within 3 months of Screening
- History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer treated with watchful waiting or surgically removed non-melanoma skin cancer.
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): NCT02991144
Locations
| United States, California | |
| Ronald Reagan University of Califonria Los Angeles Medical Center | |
| Los Angeles, California, United States, 90095 | |
| University of California San Francisco | |
| San Francisco, California, United States, 94158 | |
| 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 | |
| United States, Oregon | |
| Oregon Health and Science University | |
| Portland, Oregon, United States, 97239 | |
| 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 | |
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
| 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: | March 30, 2020 |
| Last Verified: | March 2020 |
Keywords provided by Ultragenyx Pharmaceutical Inc:
|
Gene Transfer OTC Deficiency Urea Cycle Disorder |
Additional relevant MeSH terms:
|
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 |