Haemophilia A
Conditions
Interventions
Product Name: N/A
Product Code: BMN 270
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: voloctocogene roxaparvovec
CAS Number: 1819334-78-5
Current Sponsor code: BMN 270
Other descript
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Males that are 18 years or older with established severe haemophilia A as evidenced by their medical history. Patients will be considered as severe if their base FVIII level is 1 IU/dL or less 2. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs) 3. Greater or equal to 12 bleeding episodes only if receiving on-demand therapy over the previous 12 months. Does not apply to patients on prophylaxis 4. Able to sign informed consent and comply with requirements of the trial 5. No history of inhibitor, and results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months 6. Sexually active patients must be willing to use an acceptable method of contraception such as double barrier, including hormonal contraception for at least 6 months post-treatment. After 6 months, subjects may stop contraception use only if they have had 3 consecutive semen samples below the limit of detection of the test. 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 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Detectable pre-existing immunity to the AAV5 capsid as measured by AAV5 transduction inhibition or AAV5 total antibodies 2. Any evidence of active infection or any immunosuppressive disorder. 3. HIV positive 4. Significant liver dysfunction as defined by abnormal elevation of: ALT (alanine transaminase) to 3 times the upper limit of normal; Bilirubin above 3 times the upper limit of normal; Alkaline phosphatase above 3 times the upper limit of normal; or INR (international normalized ratio) = 1.4. 5. Potential participants who have had a liver biopsy in the past 3 years are excluded if they had significant fibrosis of 3 or 4 as rated on a scale of 0-4 6. Evidence of any bleeding disorder not related to Haemophilia A 7. Platelet count of < 100 x 10^9/L 8. Creatinine = 1.5 mg/dL 9. Liver cirrhosis of any etiology as assessed by liver ultrasound 10. Hepatitis B if surface antigen is positive 11. Hepatitis C if RNA is positive 12. Treatment with any IP within 30 days prior to the end of the screening period 13. Any disease or condition at the physician’s discretion that would prevent the patient from fully complying with the requirements of the study including possible corticosteroid treatment outlined in the protocol. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion. 14. Prior treatment with any vector or gene transfer agent 15. Major surgery planned in the 16-week period following the viral infusion 16. Use of systemic immunosuppressive agents or live vaccines within 30 days before the viral infusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the safety of a single intravenous administration of a recombinant AAV5 encoding human coagulation FVIII (AAV5-hFVIII-SQ) vector. - To determine the dose of AAV5-hFVIII-SQ required to achieve FVIII at or above 5% of normal activity (=5 IU/dL) at 16 weeks after infusion. The kinetics, duration and magnitude of AAV-mediated FVIII activity in individuals with haemophilia A will be determined and correlated to an appropriate BMN 270 dose.;Secondary Objective: - To describe the immune response to the FVIII transgene and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ - To assess the impact of BMN 270 on the frequency of FVIII replacement therapy during the study - To assess the impact of BMN 270 on the number of bleeding episodes requiring treatment during the study;Primary end point(s): - To assess the safety of a single intravenous administration of a recombinant AAV5 encoding human coagulation FVIII (AAV5-hFVIII-SQ) vector. - To determine the dose of AAV5-hFVIII-SQ required to achieve FVIII at or above 5% of normal activity (=5 IU/dL) at 16 weeks after infusion. The kinetics, duration and magnitude of AAV-mediated FVIII activity in individuals with haemophilia A will be determined and correlated to an appropriate BMN 270 dose.;Timepoint(s) of evaluation of this end point: Safety will be closely monitored during dosing and for 24 hours after dosing. Safety follow-up evaluations will be conducted at least once a week after the infusion for 36 weeks, once every 2 weeks until the end of the first year and then once every three months until the end of the study (in year 7). Dose determination will be evaluated using FVIII activity assays and will be assessed weekly during the first 36 weeks after the infusion, once every 2 weeks until the end of the first year and then once every three months until the end of year 5. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To describe the immune response to the FVIII transgene and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ - To assess the impact of BMN 270 on the frequency of FVIII replacement therapy during the study - To assess the impact of BMN 270 on the number of bleeding episodes requiring treatment during the study ;Timepoint(s) of evaluation of this end point: Immune responses will be assessed every week through Week 20, then every other week through Week 36, then once every 2 months until the end of the first year and then once every three months until the end of year 5 and then every 26 weeks until the end of the study (in year 7). The impact of BMN 270 on the frequency of FVIII replacement therapy and number of bleeding episodes will be assessed at each visit by providing diaries to participants to record these events. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Information
BioMarin Pharmaceutical Inc.
Outcome results
None listed