Hemophilia B MedDRA version: 20.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: AAV5-hFIXco-Padua
Product Code: AMT-061
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: etranacogene dezaparvovec
Sponsors
uniQure biopharma B.V.
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 three 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 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
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 Visit 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 extracellular antigen (HBeAg), • 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 × 109/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 FIX products - Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients - 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: The primary objective is to demonstrate the effect of AMT-061 on endogenous factor IX (FIX) activity 6 months after a single AMT-061 treatment.; Secondary Objective: 1. Demonstrate non-inferiority of AMT-061 as compared to standard of care continuous routine (CR) FIX prophylaxis in terms of bleeding prevention Investigating effect of 2 x 10^13 gc/kg AMT-061 on - Bleeding prevention - Trough FIX activity - Discontinuation of previous CR prophylaxis - Consumption of FIX replacement therapy - Occurrence & resolution of target joints - Correlation of FIX activity levels after dosing & pre-IMP anti-AAV5 antibody titers - Endogenous FIX activity 52 weeks after dosing. - Exploratory efficacy objectives 2. Demonstrate additional efficacy and safety aspects of systemic administration of AMT-061. - monitoring of AEs - formation of anti-AAV5 antibodies (total IgM & IgG neutralizing antibodies) - AAV5 capsid-specific T cell response - anti-FIX antibodies - FIX inhibitors - hematology & serum chemistry - shedding of vector DNA (blood & semen) - inflammatory markers - AST/ALT increase (corticosteroids use required to preserve FIX activity) ;Primary end point(s): Endogenous factor IX activity after AMT-061 dosing;Timepoint(s) of evaluation of this end point: 26 weeks after AMT-061 dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints - ABR comparison between AMT-061 and prophylaxis for non-inferiority between the lead-in and the 52 week post-treatment (AMT-061) followup - Annualized consumption of factor IX replacement therapy during the 52-week post-treatment follow-up, 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-week post-treatment follow-up - Comparison of the percentage of subjects with trough factor IX activity <12% of normal between the lead-in phase and after treatment with AMT-061 at Week 26 - Endogenous factor IX activity at 52 weeks after AMT-061 dosing - ABR comparison between AMT-061 and prophylaxis for superiority between the lead-in and the 52-week post-treatment (AMT-061) follow-up - Rate of spontaneous (unprovoked) bleeding events during the 52-week post-treatment follow-up compared to lead-in phase - Rate of joint bleeding events during the 52-week post-treatment follow-up compared to the lead-in phase - Occurrence and resolution of target joints during the 52 weeks following AMT-061 dosing - Correlation of factor IX activity levels during the 52-week post-treatment follow-up with pre-IMP anti AAV5 antibody titers using the luciferase based NAB assay - Rate of traumatic (provoked) bleeding events during the 52-week post-treatment follow-up compared to the lead-in phase - Patient reported outcome (PRO) questionnaires: EuroQol (EQ-5D-5L) and iPAQ Secondary safety endpoints - Adverse events - Anti-AAV5 antibodies (total [IgM and IgG], neutralizing antibodies) - AAV5 capsid-specific T cells - | — |
Countries
Belgium, Canada, Denmark, Finland, France, Germany, Ireland, Italy, Netherlands, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
uniQure biopharma B.V.
Outcome results
None listed