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

JRCT ID: jRCT2073220097

Registered date:30/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: late-onset Ornithine Transcarbamylase (OTC) Deficiency
• Date of first enrollment: 01/03/2023
• Target sample size: 6
• Countries of recruitment: Argentina,Japan,Australia,Japan,Brazil,Japan,Canada,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Portugal,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Gene Therapy Products: DTX301
On Day1, subjects will receive a single, blinded, peripheral IV infusion of IP (DTX301 / Placebo).
At Week 64, subjects will receive a second blinded infusion of IP (DTX301 / Placebo).
Subjects randomly assigned to DTX301 at Day1 will receive placebo at Week 64, while subjects randomly assigned to placebo at Day1 will receive a single, blinded, peripheral IV infusion of DTX301 Week 64.

Outcome(s)

Primary Outcome

- Percentage of Participants at Week 64 Who Have Achieved Complete Response (DTX301 vs Placebo)
- Plasma Ammonia as Measured by 24-hour Ammonia (AUC0-24) at Week 64

Secondary Outcome

- Percentage of Participants at Week 64 Who Have Achieved Complete Response, Response, or No Response
- PGIC-Overall Change score at Week 64
- Rate of Hyperammonemic Crises (HACs) from Baseline to Week 64 Compared to Pre-enrollment
- Change in Plasma Ammonia (AUC0-24) After 64 weeks of DTX301 exposure
- Change in Plasma Ammonia (AUC0-24) From Baseline to Week 64 For All Participants
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs, Related Serious TEAEs and Adverse Events of Special Interest (AESIs)
- Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Physical Examination Results, and Vital Sign Measurements
- Number of Participants With Anti-OTC Antibodies

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include 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)
- Documented history of more than 1 symptomatic hyperammonemia episode.
- Patient is currently receiving ammonia scavenger therapy and/or protein-restricted diet, is free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
- Plasma 24-hour ammonia (AUC0-24) is 4800 micro-mol*h/L or under at screening
- If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for 4 weeks or more 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 or more 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

Exclude criteria

- Significant hepatic inflammation or cirrhosis
- Estimated glomerular filtration rate less than 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 older or the Schwartz bedside formula (Schwartz and Work, 2009) for subjects younger than 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 confound interpretation of results
- Participation (current or previous) in another gene transfer study
Note: Additional inclusion/exclusion criteria may apply, per protocol

Related Information

• Primary Sponsor: Kajiwara Makoto
• Secondary ID(s): NCT05345171,2020-003384-25