Pharmacokinetic Comparison of Efanesoctocog Alfa vs Other EHL-rFVIII Products in Participants With Severe Haemophilia A
- Registration Number
- NCT06579144
- Lead Sponsor
- Swedish Orphan Biovitrum
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 24
- 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 activitiy 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.
- 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 greated 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Damactocog alfa pegol Efanesoctocog alfa Patients treated with damactocog alfa pegol at the time of screening will receive one single injection with 50 IU/kg at visit 1, then one single dose 50 IU/kg with efanesoctocog alfa at visit 8. Turoctocog alfa pegol Efanesoctocog alfa Patients treated with turoctocog alfa pegol at the time of screening will receive one single injection with 50 IU/kg at visit 1, then one single dose 50 IU/kg with efanesoctocog alfa at visit 8.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (2)
Sobi Investigational site
🇩🇪Frankfurt, Germany
Sobi Investigational Site
🇪🇸Zaragoza, Spain