Haemophilia B MedDRA version: 20.0 Level: LLT Classification code 10018939 Term: Haemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: AAV5-hFIX
Product Code: AMT-060
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not available yet
Current Sponsor code: AMT-060
Other descriptive name: AAV5-HFIX
Concentr
Sponsors
uniQure biopharma B.V.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male 2. Age = 18 years 3. Patients with congenital haemophilia B classified as one of the following: - Known severe FIX deficiency with plasma FIX activity level =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. History of positive FIX inhibitors test 2. Positive FIX inhibitors test = 0.6 BU/mL at Screening (measured by the local laboratory) 3. Neutralizing antibodies against AAV5 at Screening (measured by the central laboratory) 4. Screening laboratory values (measured by the central laboratory): a. ALT > 2 times upper normal limit b. AST > 2 times upper normal limit c. total bilirubin > 2 times upper normal limit d. ALP > 2 times upper normal limit e. creatinine > 1.5 times upper normal limit 5. Positive HIV serological test at Screening, not controlled with anti-viral therapy as shown by CD4+ counts = 200 per µL or by a viral load of >200 copies per mL (measured by the central laboratory) 6. Active infection with Hepatitis B or C virus as reflected by Hepatitis B Surface Antigen (HBsAg), Hepatitis B extracellular Antigen (HBeAg), Hepatitis B Virus DeoxyriboNucleic Acid (HBV DNA) or Hepatitis C Virus RiboNucleic Acid (HCV RNA) positivity, respectively, at Visit 1Screening (measured by the central laboratory). 7. History of Hepatitis B or C exposure, currently controlled by antiviral therapy 8. Any coagulation disorder other than haemophilia B 9. Thrombocytopenia, defined as a platelet count below 50 × 10e9 / L, at Visit 1 (measured by the central laboratory) 10. Body mass index < 16 or = 35 kg/m2 11. Planned surgery for the initial 6 months after IMP administration in this trial 12. Previous arterial or venous thrombotic event (e.g. acute myocardial infarction, cerebrovascular disease and venous thrombosis) 13. Active severe infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, 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 14. Known significant medical condition including disseminated intravascular coagulation, fibrinolysis and liver fibrosis which, in the opinion of the investigator, may confound, contraindicate or limit the interpretation of either safety or efficacy data 15. Known history of an allergic reaction or anaphylaxis to FIX products 16. Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients 17. Previous gene therapy treatment and/or previous participation in a gene therapy clinical trial 18. Receipt of an experimental agent within 60 days prior to Visit 1 19. 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: To investigate the safety of systemic administration of AAV5-hFIX, an adeno-associated viral vector containing a codon-optimized hFIX gene, to adult patients with severe or moderately severe haemophilia B.;Secondary Objective: Secondary objectives will be addressing the efficacy and safety of systemic administration of AAV5-hFIX to adult patients with severe or moderately severe haemophilia B: Efficacy Objectives - To investigate the effect of AAV5-hFIX on FIX activity level - To investigate the effect of AAV5-hFIX on the use of FIX replacement therapy - To investigate the effect of AAV5-hFIX on bleeding episodes - To investigate the effect of AAV5-hFIX on quality of life parameters Safety Objectives - To monitor shedding of the vector in various body matrices (i.e. fluids/excretions) - To monitor the immune responses against AAV5 capsid proteins in response to AAV5-hFIX - To monitor for immune responses against FIX protein after administration of AAV5-hFIX - To investigate the effect of AAV5-hFIX on inflammatory markers;Primary end point(s): Adverse events;Timepoint(s) of evaluation of this end point: The individual subjects will be followed for five years after administration of IMP. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be addressing efficacy and safety: Confirmatory Secondary Efficacy Endpoint - FIX-replacement-therapy-free FIX activity Supportive Efficacy Endpoints - Bleeding rate - Total consumption of FIX replacement therapy - Short Form-36 (SF-36) Quality of Life (QoL) scores Safety Endpoints - Vector DNA in semen, blood, saliva, nasal secretions, urine and faeces - Neutralizing antibodies to AAV5 - Total (IgM and IgG) antibodies to AAV5 - AAV5 capsid-specific T cells - Antibodies to FIX - FIX inhibitors - Inflammatory markers: IL-1ß, IL-2, IL-6, INF?, MCP-1;Timepoint(s) of evaluation of this end point: The individual subjects will be followed for five years after administration of IMP. | — |
Countries
Denmark, Germany, Netherlands
Contacts
Public ContactRegulatory Affairs
uniQure biopharma B.V.
Outcome results
None listed