Clinical Study of DTX301 AAV- Mediated Gene Transfer for Ornithine Transcarbamylase(OTC) Deficiency

About

Brief Summary

The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels with removal of dietary protein restriction and alternative pathway medication.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 3

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

12 Years

Maximum Age

N/A

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 (ie, OTC analysis)
Free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening
If on a protein-restricted diet, must be on a stable total daily protein intake that does not vary more than 20% for ≥ 4 weeks prior to screening
From the time written informed consent through Week 128, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not father a child or donate sperm

Key Exclusion Criteria:

Significant hepatic inflammation or cirrhosis
Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening by the 2021 CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of age or the Schwartz bedside formula (Schwartz and Work, 2009) for patients < 18 years of age
Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity
Active infection (viral or bacterial)
Detectable pre-existing antibodies to the AAV8 capsid
Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
Participation (current or previous) in another gene transfer study