Clinical Trials List
Protocol Number270-302
NCT Number(ClinicalTrials.gov Identfier)NCT03392974
2019-03-14 - 2019-09-25
Phase III
Terminated5
ICD-10D66
Hereditary factor VIII deficiency
ICD-9286.0
Congenital factor VIII disorder
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
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Trial Applicant
TAIWAN PSI HEALTH DEVELOPMENT COMPANY LIMITED
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Sponsor
BioMarin Pharmaceutical Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 張平穎 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 施銘洋 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Pei-Chin Lin Division of Pediatrics
- 許琬宜 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Hemophilia A
Objectives
The primary efficacy objective of the study is to:
• Assess the efficacy of BMN 270 defined as FVIII activity, as measured by
chromogenic substrate assay, during Weeks 49-52 following intravenous infusion of BMN 270
The secondary efficacy objectives of the study are to:
• Assess the impact of BMN 270 on usage of exogenous FVIII replacement therapy from Week 5 to Week 52
• Assess the impact of BMN 270 on the number of bleeding episodes requiring
exogenous FVIII replacement therapy from Week 5 to Week 52
The tertiary efficacy objective of the study is to:
• Assess the impact of BMN 270 on patient-reported outcomes (PROs) at Week 52 of the study compared to baseline
The safety objectives of the study are to:
• Evaluate the safety of BMN 270 during the first 52 weeks following intravenous infusion
• Assess the long-term safety of BMN 270
Test Drug
BMN 270
Active Ingredient
AAV5-hFVIII-SQ
Dosage Form
soluiton for IV infusion
Dosage
4E13 vg/kg
Endpoints
Primary Outcome Measures :
Change of the median Factor VIII (FVIII) activity [ Time Frame: 52 Weeks ]
Secondary Outcome Measures :
Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy [ Time Frame: 52 weeks ]
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment [ Time Frame: 52 weeks ]
Change of the median Factor VIII (FVIII) activity [ Time Frame: 52 Weeks ]
Secondary Outcome Measures :
Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy [ Time Frame: 52 weeks ]
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment [ Time Frame: 52 weeks ]
Inclution Criteria
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 previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) (or less than 1.0 BU for laboratories with a historical lower
sensitivity cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week apart within the past 12 months (at least one of which should be tested at the central laboratory).
6. Sexually active participants must agree to use an acceptable method of effective contraception, either 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.
Participants must agree to contraception use for at least 12 weeks post-infusion; after 12 weeks, 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.
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 previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) (or less than 1.0 BU for laboratories with a historical lower
sensitivity cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week apart within the past 12 months (at least one of which should be tested at the central laboratory).
6. Sexually active participants must agree to use an acceptable method of effective contraception, either 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.
Participants must agree to contraception use for at least 12 weeks post-infusion; after 12 weeks, 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.
Exclusion Criteria
1. Detectable pre-existing antibodies to the AAV5 capsid.
2. Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.
3. Significant liver dysfunction with any of the following abnormal laboratory results:
• ALT (alanine aminotransferase) > 1.25x ULN;
• AST (aspartate aminotransferase) > 1.25x ULN;
• GGT (gamma-glutamyltransferase) > 1.25x ULN;
• Total bilirubin > 1.25x ULN;
• Alkaline phosphatase > 1.25x ULN; or
• INR (international normalized ratio) ≥ 1.4.
Subjects whose liver laboratory assessments fall outside of these ranges may undergo
repeat testing of the entire liver test panel within the same Screening window and, if
eligibility criteria are met on retest, may be enrolled after confirmation by 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 109 /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 (HBsAg,
HBsAb, and HBcAb) 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 or hypersensitivity to BMN 270 investigational product formulation.
20. Unwilling to receive blood or blood products for treatment of an adverse event and/or
a bleeding episode.
2. Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.
3. Significant liver dysfunction with any of the following abnormal laboratory results:
• ALT (alanine aminotransferase) > 1.25x ULN;
• AST (aspartate aminotransferase) > 1.25x ULN;
• GGT (gamma-glutamyltransferase) > 1.25x ULN;
• Total bilirubin > 1.25x ULN;
• Alkaline phosphatase > 1.25x ULN; or
• INR (international normalized ratio) ≥ 1.4.
Subjects whose liver laboratory assessments fall outside of these ranges may undergo
repeat testing of the entire liver test panel within the same Screening window and, if
eligibility criteria are met on retest, may be enrolled after confirmation by 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 109 /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 (HBsAg,
HBsAb, and HBcAb) 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 or hypersensitivity to BMN 270 investigational product formulation.
20. Unwilling to receive blood or blood products for treatment of an adverse event and/or
a bleeding episode.
The Estimated Number of Participants
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Taiwan
12 participants
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Global
40 participants
