Hemophilia A With Anti Factor VIII, Hemophilia A With Inhibitor
Conditions
Keywords
Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic DIseases, Factor VIII, Coagulants, Hemophilia A, AAV5 vector
Brief summary
This Phase I/II clinical study will evaluate the safety and efficacy of valoctocogene roxaparvovec in patients with severe haemophilia A and inhibitors to FVIII. Part A of the study will involve subjects who have active inhibitors to FVIII, and Part B involving subjects with a prior history of inhibitors.
Interventions
BIOLOGICALValoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males ≥ 18 years of age with hemophilia A and documented prior residual FVIII activity ≤ 1 IU/dL including, but not limited to, at the time of detected inhibitors, at the time of signing the informed consent. 2. History of a positive inhibitor result with the first positive result at least 12 month prior to Screening. Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B: Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer \< 0.6 BU. 3. Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor \& hemophilia therapy Hx over previous 12 months. 4. Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion. 5. Willing to abstain from consumption of alcohol 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; patients with HIV infection and undetectable viral load are not excluded. 3. Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only). 4. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy. 5. Evidence of any bleeding disorder not related to hemophilia A.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 after administration of BMN 270. | 60 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of the median Factor VIII activity. | 60 months | Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay. |
| A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270. | 60 months | FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay. |
| Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270. | 60 months | FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay. |
| Change in the annualized utilization of hemophilia therapy after administration of BMN 270 | 60 months | — |
| Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270. | 60 months | — |
Countries
Brazil, Israel, South Korea, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Monitor, MD
BioMarin Pharmaceutical
Outcome results
None listed