Hemophilia A
Conditions
Keywords
Haemophilia A, Blood coagulation disorder, efanesoctocog alfa, FVIII, Coagulation protein disorder, Pharmacokinetics
Brief summary
Sobi.BIVV001-003 is an open-label, 2-period, fixed sequence study for intra-participant comparison of the PK profiles of efanesoctocog alfa and the extended half-life rFVIII products damactocog alfa pegol or turoctocog alfa pegol after a single i.v. injection in previously treated males, 18-65 years of age, with severe haemophilia A. Participants who are receiving treatment with damoctocog alfa pegol (n\ 12) or turoctocog alfa pegol (n\ 12) will be enrolled in the study. The study will start with a screening period (up to 28 days), including a wash-out period prior to start of the actual study period. During the the first visit, a single dose of damactocog alfa pegol or turoctocog alfa pegol (corresponding to the participant's pre-study treatment) will be administered. A PK sampling period will follow over 7 visits. Following completion of the PK sampling of the original treatment regimen, the patients will be given a single dose of efanesoctocog alfa at visit 8, after which a new PK sampling period will follow (visit 8-15). The primary objective for the study is to compare the half-life of efanesoctocog alfa with that of the two comparator drugs after a single iv. injections. Secondary objectives include comparison of area under the curve for efanesoctocog alfa vs. the two comparator drugs, characterization of PK parameters for all three drugs as well as well as to evaluate safety and tolerability of a single iv. injection of efanesoctocog alfa.
Interventions
Recombinant coagulation factor VIII Fc-von Willebrand Factor-XTEN fusion protein (rFVIIIFc-VWF-XTEN)
Sponsors
Swedish Orphan Biovitrum
PSI CRO
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Open-label, 2-period, fixed-sequence study for intra-participant comparison of PK-profiles.
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be male, 18 to 65 years of age, inclusive, at the time of signing the informed consent form (ICF). * Severe haemophilia A, defined as \<1 IU/dL (\<1%) endogenous FVIII activity, as documented in historical medical records from a clinical laboratory demonstrating \<1% FVIII coagulant activity or a documented genotype known to produce severe haemophilia A. * Previous treatment for haemophilia A with any marketed recombinant and/or plasma derived FVIII for at least 150 exposure days. * Currently receiving treatment with damoctocog alfa pegol or turoctocog alfa pegol at Screening.
Exclusion criteria
* Any history of a positive inhibitor test, defined as \>0.6 Bethesda units (BU)/mL in at least two consecutive Bethesda inhibitor assays, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL. Family history of inhibitors will not exclude the participant. * Positive FVIII inhibitor result (assessed by central laboratory), defined as ≥0.6 BU/mL at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Half-life (t½) of efanesoctocog alfa, damactocog alfa pegol and turoctocog alfa pegol after a single i.v. injection | up to 7 days and 14 days after the administration of the respective drugs. | PK assessments will be based on FVIII activity levels determined by one-stage clotting assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare the area under the curve zero to infinity (AUC∞) of efanesoctocog alfa with that of damoctocog alfa pegol and with that of turoctocog alfa pegol after a single i.v. injection. | up to 7 days and 14 days after the administration of the respective drugs. | The area under the curve will be calculated based on drug concentration analyses from time zero to last quantifiable sample collection timepoint |
| To characterize Cmax of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Maximum concentration observed (Cmax) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize clearance of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Clearance of drug/s (CL) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize volume of distribution of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Volume of distribution (Vd) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize mean residence time of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Mean residence time (MRT) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize incremental recovery of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Incremental Recovery (IR) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize time to specific plasma FVIII levels of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Time to specific plasma FVIII:C levels (40%, 20%, and 10%) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To characterize time spent in plasma FVIII:C normal range for efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection. | up to 7 days and 14 days after the administration of the respective drugs. | Time to spent in plasma FVIII:C normal range (50% - 150%) assessed by FVIII activity measurement by one-stage aPTT clotting assay |
| To evaluate the safety and tolerability of a single IV injection of efanesoctocog alfa. | From first dose of comparator to end of study, approximately 1 month. | All safety data from visit 1 up until the dose of efanesoctocog alfa for the first treatment period and then subsequently all safety data from the dose of efanesoctocog alfa until EoS will be analyzed for this outcome measure. |
Countries
Bulgaria, Germany, Italy, Spain
Contacts
STUDY_DIRECTORElena Santagostino, MD
Sobi AB
Outcome results
None listed