Hemophilia B MedDRA version: 20.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: HEMGENIX®
Product Name: AAV5-hFIXco-Padua
etranacogene dezaparvovec
Product Code: CSL222 (AMT-061)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: etranacogene dezaparvovec
CAS Number: No
Current Sponsor code: CSL222 (formerly
Sponsors
CSL Behring LLC
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Male - Age =18 years - Subjects with congenital hemophilia B with known severe or moderately severe factor IX deficiency (=2% of normal circulating factor IX ) for which the subject is on continuous routine factor IX prophylaxis (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). - >150 previous exposure days of treatment with factor IX protein - Have been on stable prophylaxis for at least 2 months prior to screening - Have demonstrated capability to independently, accurately and in a timely manner complete the diary during the lead-in phase as judged by the investigator - 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 3 consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized) - Able to provide informed consent following receipt of verbal and written information about the trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: - History of factor IX inhibitors - Positive factor IX inhibitor test at screening and Visit L-Final (based on local laboratory results) - Screening and Visit L-Final laboratory values (based on central laboratory results): a. ALT >2 times upper normal limit b. Aspartate aminotransferase (AST) >2 times upper normal limit c. Total bilirubin >2 times upper normal limit (except if this is caused by Gilbert disease) d. Alkaline phosphatase (ALP) >2 times upper normal limit e. Creatinine >2 times upper normal limit - Positive human immunodeficiency virus (HIV) serological test at screening and Visit LFinal, not controlled with anti-viral therapy as shown by CD4+ counts = 200/µL (based on central laboratory results) - 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) - Known coagulation disorder other than hemophilia B - Thrombocytopenia, defined as a platelet count below 50 × 10^9/L, at screening and Visit L-Final (based on central laboratory results) - 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 - 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; e.g. a FibroScan™ score of =9 kPa is considered equivalent) - Known history of an allergic reaction or anaphylaxis to factor IX products - Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients - Known history of allergy to corticosteroids - Known medical condition that would require chronic administration of steroids - Previous gene therapy treatment - Receipt of an experimental agent within 60 days prior to screening - Current participation or anticipated participation within one year after IMP administration in this trial in any other interventional clinical trial involving drugs or devices.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: demonstrate the non-inferiority of CSL222 (formerly AMT-061 [2 x 10^13 gc/kg]) during the 52 weeks following establishment of stable factor IX expression (months 6 to 18) post-treatment (CSL222) follow-up compared to standard of care continuous routine factor IX prophylaxis during the lead-in phase, as measured by the annualized bleeding rate (ABR). ;Secondary Objective: The secondary objective is to demonstrate additional efficacy and safety aspects of systemic administration of CSL222 (formerly AMT-061) on: - Endogenous factor IX activity 6 months, 12 months, and 18 months - Bleeding prevention - Trough FIX activity - Discontinuation of previous continuous routine prophylaxis - Consumption of FIX replacement therapy - Occurrence & resolution of target joints - Estimated ABR during the 52 weeks following stable factor IX expression - Correlation of pre-IMP anti-AAV5 antibody titers - Exploratory efficacy objectives Safety objectives include: - monitoring of AEs - changes in abdominal ultrasound - formation of anti-AAV5 antibodies (total IgM & IgG neutralizing antibodies) - AAV5 capsid-specific T cell response - anti-FIX antibodies - FIX inhibitors and recovery - hematology & serum chemistry - shedding of vector DNA (blood & semen) - inflammatory markers - AST/ALT increase and alpha-fetoprotein (AFP);Primary end point(s): ABR comparison between CSL222 (formerly: AMT-061) and prophylaxis for non-inferiority between the lead-in phase and the 52 weeks following stable factor IX expression (months 6-18 post treatment);Timepoint(s) of evaluation of this end point: Comparison between 52-week post-treatment follow-up and the lead-in phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints - Endogenous factor IX activity at 6 months after CSL222 dosing - Endogenous factor IX activity at 12 months after CSL222 dosing - Endogenous factor IX activity at 18 months after CSL222 dosing - Annualized consumption of factor IX replacement therapy during the 52 weeks following stable factor IX expression (months 6-18 post- treatment), excluding factor IX replacement for invasive procedures, compared to the lead-in phase - Annualized infusion rate of factor IX replacement therapy during the 52 weeks following stable factor IX expression (months 6-18 post-treatment), excluding factor IX replacement for invasive procedures, compared to the lead-in phase - Proportion of subjects remaining free of previous continuous routine prophylaxis during the 52 weeks following stable factor IX expression (months 6-18 post-treatment) - Comparison of the percentage of subjects with trough factor IX activity <12% of normal between the lead in phase and after treatment with CSL222 over the 52 weeks following stable factor IX expression (months 6-18 post-treatment) - ABR comparison between CSL222 and prophylaxis for superiority between the lead-in phase and the 52 weeks following stable factor IX expression (months 6-18 post-treatment) - Rate of spontaneous bleeding events during the 52 weeks following stable factor IX expression (months 6-18 post-treatment) compared to the lead in phase - Rate of joint bleeding events during the 52 weeks following stable factor IX expression (months 6-18 post treatment) compared to the lead-in phase - Estimated ABR – during the 52 weeks following stable factor IX expression (months 6-18 post-treatment) – as a function of pre-IMP anti-AAV5 antibody titers using the luciferase based NAB assay (as a “correlation” analysis) - Correlation of factor IX activity levels during the 52 weeks following stable factor IX expression (months 6-18 post-treatment) with pre-IMP anti-AAV5 antibody titers using the | — |
Countries
Belgium, Denmark, Germany, Ireland, Italy, Netherlands, Sweden, United Kingdom, United States
Contacts
Public ContactTrial Registration Coordinator
CSL Behring LLC
Outcome results
None listed