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

Key Inclusion Criteria:

- Confirmed clinical diagnosis of late-onset OTC deficiency with historical
documentation via 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

- Plasma spot ammonia level on Day 1 (predose) is ≤ 200 µmol/L

- 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 CKD EPI
creatinine-based formula (Levey et al., 2009) for subjects ≥ 18 years of age or the
Schwartz bedside formula (Schwartz and Work, 2009) for subjects < 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

Note: Additional inclusion/exclusion criteria may apply, per protocol