Phase III, open-label, single-dose, multi-center multinational trial investigating a serotype 5 adeno-associated viral vector containing the Padua variant of a codon-optimized human factor IX gene (AAV5-hFIXco-Padua, AMT-061) administered to adult subjects with severe or moderately severe hemophilia B

Phase 3

Recruiting

• Conditions: Bleeder's disease; 10005330; Christmas disease; 10064477

• Registration Number: NL-OMON52495
• Lead Sponsor: CSL Behring LCC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

1. Male
2. Age >=18 years
3. Subjects 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 Factor IX prophylaxis*
4. >150 previous exposure days of treatment with FIX protein
5. Have been on stable prophylaxis for at least 2 months prior to screening
6. Have demonstrated capability to independently, accurately and in a timely
manner complete the diary during the lead-in phase as judged by the investigator
7. Acceptance to use a condom during sexual intercourse in the period from IMP
administration until AAV5 has been cleared from semen, as evidenced by the
central laboratory from negative analysis results for at least three
consecutively collected semen samples (this criterion is applicable also for
subjects who are surgically sterilized)
8. Able to provide informed consent following receipt of verbal and written
information about the trial,

*Continuous routine prophylaxis is defined as the intent of treating with an a
priori defined frequency of infusions (e.g., twice weekly, once every two
weeks, etc.) as documented in the medical records

Exclusion Criteria

1. History of FIX inhibitors
2. Positive FIX inhibitor test at screening and Visit L-Final (based on local
laboratory results)
3. Screening and Visit L-Final laboratory values (based on central laboratory
results):
a. ALT >2 times ULN
b. Aspartate aminotransferase (AST) >2 times ULN
c. Total bilirubin >2 times ULN (except if this is caused by Gilbert disease)
d. Alkaline phosphatase (ALP) >2 times ULN
e. Creatinine >2 times ULN limit
4. Positive human immunodeficiency virus (HIV) serological test at screening
and Visit L-Final, not controlled with anti-viral therapy as shown by CD4+
counts <= 200/µL (based on central laboratory results)
5. 5. Hepatitis B or C infection with the following criteria present at
screening:
i. Currently receiving antiviral therapy for this/these infection(s)
and/or
ii. Positive for any of the following (based on central laboratory results):
• Hepatitis B surface antigen (HBsAg), except if in the opinion of the
investigator this is due to a previous Hepatitis B vaccination rather than
active Hepatitis B infection
• Hepatitis B virus deoxyribonucleic acid (HBV DNA)
• Hepatitis C virus ribonucleic acid (HCV RNA)
6. Known coagulation disorder other than hemophilia B
7. Thrombocytopenia, defined as a platelet count below 50 × 109/L, at screening
and Visit L-Final (based on central laboratory results)
8. Known severe infection or any other significant concurrent, uncontrolled
medical condition including, but not limited to, renal, hepatic,
cardiovascular, hematological, gastrointestinal, endocrine, pulmonary,
neurological, cerebral or psychiatric disease, alcoholism, drug dependency or
any other psychological disorder evaluated by the investigator to interfere
with adherence to the protocol procedures or with the degree of tolerance to
the IMP
9. Known significant medical condition that may significantly impact the
intended transduction of the vector and/or expression and activity of the
protein, including but not limited to:
• Disseminated intravascular coagulation
• Accelerated fibrinolysis
• Advanced liver fibrosis (suggestive of or equal to METAVIR Stage 3 disease; a
FibroScan* score of >=9 kPa is considered equivalent)
10. Known history of an allergic reaction or anaphylaxis to factor IX products
11. Known history of allergy to corticosteroids
12. Known uncontrolled allergic conditions or allergy/hypersensitivity to any
component of the IMP excipients
13. Known medical condition that would require chronic administration of
steroids
14. Previous gene therapy treatment
15. Receipt of an experimental agent within 60 days prior to screening
16. Current participation or anticipated participation within one year after
IMP administration in this trial in any other interventional clinical trial
involving drugs or devices.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoints<br /><br>- ABR comparison between CSL222 (formerly AMT-061) and prophylaxis for<br /><br>non-inferiority between the lead-in phase and the 52 weeks following stable<br /><br>factor IX expression (months 6-18 post treatment)</p><br>