Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as DTX301
scAAV8OTC · 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...
scAAV8OTC is an investigational gene therapy being developed for the treatment of Ornithine Transcarbamylase (OTC) Deficiency, a rare inherited metabolic disorder. It is designed to address the underlying genetic cause of the condition. The drug is currently in clinical development and has not been approved by regulatory authorities.
scAAV8OTC is a gene therapy that uses an adeno-associated virus serotype 8 (AAV8) vector to deliver a functional copy of the ornithine transcarbamylase (OTC) gene to liver cells. This aims to restore the activity of the OTC enzyme, which is deficient in patients with OTC Deficiency, thereby helping to normalize ammonia metabolism.
scAAV8OTC is being developed by Ultragenyx Pharmaceutical Inc., a biopharmaceutical company focused on rare diseases. The company's stock is traded under the ticker symbol RARE. The drug is also known as DTX301, and it is being investigated as a potential treatment for OTC Deficiency.
scAAV8OTC is in Phase 1 clinical development. A Phase 1 trial has been completed, which was a safety and dose-finding study in adults with late-onset OTC Deficiency. The drug is still investigational and has not received FDA approval. Further clinical development would be required before it could be considered for regulatory submission.
scAAV8OTC has been studied in one clinical trial with the identifier NCT02991144. This was a Phase 1, controlled, open-label study titled 'Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset Ornithine Transcarbamylase (OTC) Deficiency.' The trial enrolled 16 participants and was conducted in the United States, Canada, Spain, and the United Kingdom. The study has been completed.
Yes, scAAV8OTC is also known as DTX301. The two names refer to the same investigational gene therapy being developed by Ultragenyx Pharmaceutical Inc. for the treatment of OTC Deficiency. In clinical trial records, the drug is often referred to as DTX301, while scAAV8OTC describes its composition as an AAV8 vector carrying the OTC gene.