Phase 3, Open-label, Single-dose, Study of AAV5-hFIXco-Padua, CSL222, in Japanese Adult Male Subjects with Severe or Moderately Severe Hemophilia B

JRCT ID: jRCT2033230266

Registered date:29/07/2023

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: Hemophilia B
• Date of first enrollment: 28/09/2023
• Target sample size: 4
• Study type: Interventional
• Intervention(s): Single intravenous dose of CSL222 (AAV5-hFIXco-Padua; etranacogene dezaparvovec)

Outcome(s)

• Primary Outcome: Annualized bleeding rate (ABR) for CSL222 and Lead-in FIX prophylaxis.

Secondary Outcome

Efficacy
1.Endogenous FIX activity.
2.Annualized consumption of FIX replacement therapy.
3.Annualized infusion rate of FIX replacement therapy.
4.Number of subjects remaining free of continuous routine FIX prophylaxis.
5.Number of subjects with FIX activity < 12% of normal.
6.Annualized spontaneous bleeding rate.
7.Annualized joint bleeding rate.
8.ABR for FIX-treated bleeding episodes.
9.Association of FIX activity levels with pre-CSL222 AAV5 neutralizing antibody (NAb) titers.
10.Occurrence of new target joints and resolution of preexisting target joints.
11.Number of subjects with zero bleeds and zero FIX-treated bleeds.
12.Number of bleeding episodes in the first 6 months

Safety
1.Adverse events.
2.Changes in liver ultrasound (every 6 months).
3.Total antibodies (immunoglobulin M and immunoglobulin G) to AAV5 and AAV5 NAbs.
4.AAV5 capsid-specific T cells.
5.Anti-FIX antibodies.
6.FIX inhibitors.
7.FIX recovery.
8.Hematology and biochemistry parameters.
9.ALT / AST levels.
10.Corticosteroid use for ALT / AST increases.
11.Vector DNA in blood and semen.
12.Inflammatory markers: interleukin 1-beta, interleukin 2, interleukin 6, interferon-gamma, monocyte chemoattractant protein-1.
13.Alpha-fetoprotein.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

Assigned male at birth, age >= 18 years, of Japanese origin
Subject with congenital hemophilia B with known severe or moderately severe FIX deficiency (<= 2% of normal circulating FIX) for which the subject is on continuous routine FIX prophylaxis
> 150 previous exposure days of FIX replacement therapy

Exclude criteria

History of FIX inhibitors
Positive human immunodeficiency virological test
Hepatitis B or C infection
Known coagulation disorder other than hemophilia B

Related Information

• Primary Sponsor: Akama Hideto