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Also known as avalotcagene ontaparvovec, scAAV8OTC
DTX301 · 2 trials · 2 indications
AE: any untoward medical occurrence regardless of its causal relationship to study product. TEAE: any event not present before exposure to study product or any event already present that worsens in either intensity or frequency after exposure to study product. SAE: 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; is an important medical event, according to the investigator. AE intensity was rated as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life threatening), or 5 (death) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). The relationship or association of the study product in causing or contributing to the AE was characterized as: unrelated; possible; probably; definite.
| Arm | Type | Description |
|---|---|---|
| DTX301 | EXPERIMENTAL | Participants receive single peripheral intravenous (IV) infusion of DTX301 in solution. Between Week 36 and Week 64, participants may receive single peripheral IV infusion of placebo. |
| Placebo, Then DTX301 | EXPERIMENTAL | Participants receive single peripheral IV infusion of placebo. Between Week 36 and Week 64, participants receive single peripheral IV infusion of DTX301 in solution. |
| Cohort 1: DTX301 2.0 × 10^12 GC/kg | EXPERIMENTAL | DTX301 (scAAV8OTC) 2.0 × 10\^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis. |
| Cohort 2: DTX301 6.0 × 10^12 GC/kg | EXPERIMENTAL | DTX301 (scAAV8OTC) 6.0 × 10\^12 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis. |
| Cohort 3: DTX301 1.0 × 10^13 GC/kg | EXPERIMENTAL | DTX301 (scAAV8OTC) 1.0 × 10\^13 GC/kg will be administered as a single peripheral IV infusion. A reactive corticosteroid taper regimen will be administered to control transient vector-induced hepatic effects. Sodium acetate will be used as a tracer to measure the rate of ureagenesis. |
| Cohort 4: DTX301 1.0x10^13 GC/kg + Prophylactic Corticosteroids | EXPERIMENTAL | A prophylactic corticosteroid taper regimen (oral prednisone \[or prednisolone\], 60 mg tapered over 9 weeks) will be administered before dosing with DTX301 (scAAV8OTC) to prevent or minimize transient vector-induced hepatic effects. DTX301 (scAAV8OTC) 1.0x10\^13 GC/kg administered as a single peripheral IV infusion. Sodium acetate will be used as a tracer to measure the rate of ureagenesis. |
| Name | Type | Description |
|---|---|---|
| DTX301 | GENETIC | non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector |
| Placebo | OTHER | normal saline infusion |
| Oral Corticosteroids | DRUG | Participants who receive DTX301 solution will receive oral corticosteroids. |
| Placebo for oral corticosteroids | DRUG | Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind |
| Sodium Acetate | DRUG | A tracer for the Ureagenesis Rate Test (URT) |
| scAAV8OTC | GENETIC | non-replicating, recombinant scAAV8 encoding human ornithine transcarbamylase (OTC) |
| Reactive Corticosteroid Taper Regimen | DRUG | Oral prednisone \[or oral prednisolone\] 60 mg/day week 1, 40 mg/day Week 2, 30 mg/day Weeks 3 and 4, tapered by 5 mg/week Week 5 and beyond until liver enzymes return to baseline levels. Corticosteroid treatment will be considered when a participant's alanine aminotransferase (ALT) level exceeded the upper limit of normal (ULN) and the ALT increase was considered by the Investigator to be related to DTX301. |
| Prophylactic Corticosteroid Taper Regimen | DRUG | Oral prednisone \[or oral prednisolone\] 60 mg/day at least 5 days prior to DTX301 administration, tapered over 9 weeks. A prophylactic corticosteroid taper regimen will be administered to prevent or minimize transient vector-induced hepatic effects. |
Key Inclusion Criteria: * Confirmed clinical diagnosis of late-onset OTC deficiency with historical documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic acid), or molecular testing...
DTX301 is an investigational gene therapy being developed for the treatment of ornithine transcarbamylase (OTC) deficiency, a rare inherited metabolic disorder. It is currently in Phase 3 clinical development and has not been approved by regulatory authorities.
DTX301 targets the OTC gene, which encodes the enzyme ornithine transcarbamylase. The therapy is designed to deliver a functional copy of this gene to address the underlying genetic cause of OTC deficiency.
DTX301 is being developed by Ultragenyx Pharmaceutical Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol RARE.
DTX301 is currently in Phase 3 clinical development. It is an investigational therapy and has not yet been approved by the FDA or other regulatory agencies.
DTX301 is being evaluated in a Phase 3 clinical trial with the identifier NCT05345171. This randomized, double-blind, controlled study is investigating the safety and efficacy of DTX301 in patients with OTC deficiency and is currently active but not recruiting.
DTX301 is an AAV-mediated gene transfer therapy specifically designed for OTC deficiency. It is the only gene therapy candidate for this condition mentioned in the available clinical trial data, and it is being studied in a Phase 3 trial.