Study of a virus transferring the gene for human OTC in patients with late-onset OTC deficiency

• Research type

  Research Study

• Full title

  A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Adeno-Associated Virus Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients with Late-Onset OTC Deficiency

• IRAS ID

  1004486

• Contact name

  Samantha Grant

• Contact email

  UKStart-upteam.SM@ppd.com

• Sponsor organisation

  Ultragenyx Pharmaceutical Inc.

• Eudract number

  2020-003384-25

• Clinicaltrials.gov Identifier

  NCT05345171

• Research summary

  Ornithine transcarbamylase (OTC) deficiency, is a rare genetic urea cycle disorder with an estimated prevalence of 1.0 to 1.9 per 100,000. OTC is a liver enzyme which helps rid the body of ammonia, a toxic breakdown product of dietary protein. In OTC deficient patients OTC pathological mutations lead to deficient enzyme activity and a reduced ability to metabolize ammonia. Acute and chronic elevations in ammonia can result in significant irreversible neurologic morbidity and mortality due to the well known toxic effect of ammonia on the brain.
  The episodic nature of OTC deficiency is an important component for developing novel treatments. DTX301 is a gene therapy being developed for the treatment of OTC deficiency that directly addresses the basis of the disease.
  Study DTX301-CL301 is sponsored by Ultragenyx Pharmaceuticals, Inc. is a Phase 3, Randomized (1:1 ratio), Double-Blind, Placebo-Controlled cross-over study to determine the efficacy and confirm the safety of DTX301 in participants 12 years of age and older with late-onset OTC deficiency.
  The study has 4 sequential phases:
   Screening (including Randomization and Baseline Assessments)
  • Primary Efficacy Analysis Period
  Day 1 IP Administration; participants receive either:
  a single, blinded, peripheral intravenous infusion of DTX301
  a single, blinded, peripheral IV infusion of normal saline
   Cross-over and Follow Up
  Week 64 IP Administration: second blinded infusion:
  participants in the DTX301 arm receive Placebo
  participants in the Placebo arm receive a single, blinded, infusion of DTX301 (for subjects still eligible for IP treatment)
   Follow-up Period to End of Study
  Approximately 50 patients worldwide, will participate in the study for about 6 years & 5 months, undergoing the following assessments: Physical examinations, Vital signs, ECG, Blood & urine sample collections, eDiary completion, Quality of Life Questionnaires, tests of memory & concentration, Entry & Exit interviews

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  23/LO/0225

• Date of REC Opinion

  13 Sep 2023

• REC opinion

  Further Information Favourable Opinion