Hemophilia A
Conditions
Keywords
Hemophilia A, Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Factor VIII, Coagulants
Brief summary
This Phase III clinical study will assess the efficacy of BMN 270 defined as FVIII activity, during weeks 49-52 following intravenous infusion of BMN 270 and assess the impact of BMN 270 on usage of exogenous FVIII replacement therapy and the number of bleeding episodes from week 5 to week 52.
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 residual FVIII levels ≤ 1 IU/dL as evidenced by medical history. 2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. 3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days. 4. No previous documented history of a detectable FVIII inhibitor of less than 0.6 Bethesda Units (BU).
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, prior liver biopsy showing significant fibrosis, liver cirrhosis of any etiology or history of hepatic malignancy. 4. Evidence of any bleeding disorder not related to hemophilia A. 5. Active Hepatitis C. 6. Prior treatment with any vector/gene transfer agent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of the Median Factor VIII (FVIII) Activity | Week 52 | Change of the FVIII activity, as measured by chromogenic substrate assay, at Week 52 post-BMN 270 infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy | Weeks 5 through Week 52 | Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy during Week 5 to Week 52 post-BMN 270 infusion from the baseline utilization of exogenous FVIII replacement therapy |
| Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment | Weeks 5 though Week 52 | Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment (annualized bleeding rate, ABR) during Week 5 to Week 52 of the study post-BMN 270 infusion from the baseline ABR |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMN 270 4E13 vg/kg Single administration of valoctocogene roxaparvovec at a dose of 4E13 vg/kg | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | BMN 270 4E13 vg/kg |
|---|---|
| Age, Continuous | 45.0 years |
| Age, Customized 18 - <65 | 1 participants |
| Age, Customized >= 65 | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White | 1 participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change of the Median Factor VIII (FVIII) Activity
Change of the FVIII activity, as measured by chromogenic substrate assay, at Week 52 post-BMN 270 infusion.
Time frame: Week 52
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BMN 270 4E13 vg/kg | Change of the Median Factor VIII (FVIII) Activity | 4.1 IU/dL |
Secondary
Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment (annualized bleeding rate, ABR) during Week 5 to Week 52 of the study post-BMN 270 infusion from the baseline ABR
Time frame: Weeks 5 though Week 52
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BMN 270 4E13 vg/kg | Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment | 5.77 episodes/year |
Secondary
Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy
Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy during Week 5 to Week 52 post-BMN 270 infusion from the baseline utilization of exogenous FVIII replacement therapy
Time frame: Weeks 5 through Week 52
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BMN 270 4E13 vg/kg | Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy | -4058.24 IU/kg/yr |