EUCTR2017-003573-34-ES进行中（未招募）1 期
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector–Mediated Gene Transfer of Human Factor VIII at a dose of 4E13 vg/kg in Hemophilia A Patients with Residual FVIII Levels = 1 IU/dL Receiving Prophylactic FVIII Infusions
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 70
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
入选标准
- •1. Males = 18 years of age with hemophilia A and residual FVIII levels = 1 IU/dL as evidenced by medical history, at the time of signing the informed consent.
- •2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and FVIII usage over the previous 12 months must be available.
- •3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
- •4. Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures.
- •5. No history of FVIII inhibitor, and results from a Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions (the most recent one of which should be tested at the central laboratory) at least one week apart within the past 12 months
- •6. Sexually active participants must agree to use an acceptable method of effective contraception -- double barrier contraception (ie, condom +diaphragm; or condom or diaphragm + spermicidal gel or foam) or their female partner either using hormonal contraceptives or having an
- •intrauterine device -- for at least 6 months post-infusion. After 6 months, subjects may stop contraception use only if they have had 3 consecutive semen samples with no detectable viral vector DNA.
- •7. Willing to abstain from alcohol consumption for at least the first 52 weeks following BMN 270 infusion.
- •8. HIV positive patients may be enrolled, only if the patient has a CD4 count > 200/mm^3 and an undetectable viral load.
- •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 70
- •F.1.3 Elderly (>=65 years) no
- •F.1.3.1 Number of subjects for this age range
排除标准
- •1. Detectable pre-existing antibodies to the AAV5 capsid.
- •2. Any evidence of active infection or any immunosuppressive disorder, except for HIV infection as described in the inclusion criterion above.
- •3. Significant liver dysfunction with any of the following abnormal laboratory results:
- •- ALT (alanine aminotransferase) or AST(aspartate aminotransferase) >2X ULN;
- •- Total bilirubin >2X ULN;
- •- Alkaline phosphatase >2X ULN; or
- •- INR (international normalized ratio) = 1.4.
- •Subjects whose liver laboratory assessments fall outside of these ranges may undergo repeat testing and, if eligibility criteria are met on retest, may be enrolled after confirmation by the Medical Monitor. In addition, subjects with abnormal laboratory results related to confirmed benign liver conditions (eg, Gilbert’s syndrome) are considered eligible for the study notwithstanding their abnormal laboratory results and may be enrolled after discussion with the Medical Monitor.
- •4. Prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
- •5. Evidence of any bleeding disorder not related to hemophilia A.
- •6. Platelet count of < 100 x 10^9/L.
- •7. Creatinine = 1.5 mg/dL.
- •8. Liver cirrhosis of any etiology as assessed by liver ultrasound.
- •9. Chronic or active hepatitis B as evidenced by positive serology testing and confirmatory HBV DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual.
- •10. Active Hepatitis C as evidenced by detectable HCV RNA or currently on antiviral therapy.
- •11. Active malignancy, except non-melanoma skin cancer.
- •12. History of hepatic malignancy.
- •13. Treatment with any Investigational Product within 30 days or 5 half lives of the investigational product prior to the screening period. For subjects who have received a prior investigational product, all ongoing adverse events (AEs) experienced while receiving that investigational product must have resolved prior to screening for this study.
- •14. Any condition that, in the opinion of the Investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including possible corticosteroid treatment outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of subject safety or efficacy result.
- •15. Prior treatment with any vector or gene transfer agent.
- •16. Major surgery planned in the 52-week period following the infusion with BMN 270.
- •17. Use of systemic immunosuppressive agents, not including corticosteroids, or live vaccines within 30 days before the BMN 270 infusion.
- •18. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol or have the potential to impact the evaluation of efficacy and safety of BMN 270 and with prior consultation with the Medical Monitor.
- •19. Known allergy
研究者
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