Brief Title
Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A
Official Title
A Phase 3b, Single Arm, Open-Label Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII, With Prophylactic Corticosteroids in Hemophilia A Patients
Brief Summary
This research study will test and confirm the safety and effectiveness of the study drug
(valoctocogene roxaparvovec) that contains the correct gene to make Factor VIII so that the
body can make its own Factor VIII that functions properly. Only one dose of valoctocogene
roxaparvovec is being given in this study, and this dose has been previously studied in
another clinical trial in patients with hemophilia A. This is a phase 3 study that is meant
to show that the study drug with prophylactic corticosteroids is safe and works to help treat
hemophilia A. The study will see if liver cells are able to make Factor VIII that functions
properly after receiving this study drug. The study will also examine the effects that the
study drug has on how much Factor VIII concentrates patients have to inject into their veins
and on their bleeding episodes after the study drug has been administered. Finally, the study
will see if and how the body responds to the study drug - for example, whether liver cells
become inflamed or whether the body makes antibodies (something the immune system makes to
protect itself against things like bacteria and viruses) against the vector or the new Factor
VIII gene.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Change of the median Factor VIII (FVIII) activity
Secondary Outcome
Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy or emicizumab
Condition
Hemophilia A
Intervention
valoctocogene roxaparvovec
Study Arms / Comparison Groups
valoctocogene roxaparvovec
Description: Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
20
Start Date
June 2020
Completion Date
December 2025
Primary Completion Date
December 2021
Eligibility Criteria
Inclusion Criteria:
- 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.
- Must have been on prophylactic hemophilia therapy for at least 12 months prior to
study entry. High-quality, well-documented historical data concerning bleeding
episodes and hemophilia therapy over the previous 12 months must be available.
- Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure
days (EDs).
- 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).
Exclusion Criteria:
- Detectable pre-existing antibodies to the AAV5 capsid.
- Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.
- 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
- 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.
- Most recent, prior FibroScan or liver biopsy showing significant fibrosis of 3 or 4 as
rated on a scale of 0 4 on the Batts Ludwig or METAVIR scoring systems, or an
equivalent grade of fibrosis if an alternative scale is used.
- Evidence of any bleeding disorder not related to hemophilia A.
- Platelet count of < 100 x 10^9/L.
- Creatinine ≥ 1.5 mg/dL.
- Liver cirrhosis of any etiology as assessed by liver ultrasound.
- Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B
surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core
antibody [HBcAb]) and confirmatory HBV DNA testing. Refer to the Centers for Disease
Control (CDC) table for the interpretation of serological test results.
- Active Hepatitis C as evidenced by detectable HCV RNA or currently on antiviral
therapy.
- Active malignancy, except non-melanoma skin cancer.
- History of hepatic malignancy.
- History of arterial or venous thromboembolic events (eg, deep vein thrombosis,
nonhemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus),
with the exception of catheter-associated thrombosis for which anti-thrombotic
treatment is not currently ongoing.
- Known inherited or acquired thrombophilia, including conditions associated with
increased thromboembolic risk, such as atrial fibrillation.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Monitor, MD, 1-800-983-4587, [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT04323098
Organization ID
BMN 270-303
Secondary IDs
2018-004616-21
Responsible Party
Sponsor
Study Sponsor
BioMarin Pharmaceutical
Study Sponsor
Medical Monitor, MD, Study Director, BioMarin Pharmaceutical
Verification Date
June 2020