臨床研究等提出・公開システム

Phase 3, Open-label, Single-dose, Multicenter Study Investigating Efficacy and Safety of a Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, CSL222) Administered to Japanese Adult Male Subjects with Severe or Moderately Severe Hemophilia B

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

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

JPN-CHIKEN@csl.com.au

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

+81-3-4213-0191

JPN-CHIKEN@csl.com.au

Not Recruiting

Sept. 29, 2023

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

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

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

Male

Hemophilia B

Single intravenous dose of CSL222 (AAV5-hFIXco-Padua; etranacogene dezaparvovec)

Annualized bleeding rate (ABR) for CSL222 and Lead-in FIX prophylaxis.

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.

July. 21, 2023

Yes

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available. Supporting Materials: Protocol and Statistical Analysis Plan will be availale. Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website. Access Criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

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