Pharmacokinetic Comparison of Efanesoctocog Alfa vs Other EHL-rFVIII Products in Participants With Severe Haemophilia A
NCT Number: NCT06579144
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Hemophilia A
Interventions: DRUG: Efanesoctocog alfa
Sponsor: Swedish Orphan Biovitrum
Collaborators: PSI CRO
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 24
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: OTHER
Start Date: 2024-09
Completion Date: 2025-04
Locations: Sobi Investigational site, Frankfurt, Germany|Sobi Investigational Site, Oldenburg, Germany|Sobi Investigational Site, Milan, Italy|Sobi Investigational Site, Naples, Italy|Sobi Investigational Site, A Coruña, Spain|Sobi Investigational Site, Valencia, Spain|Sobi Investigational Site, Zaragoza, Spain

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.

Primary Outcome Measures: Half-life (t½) of efanesoctocog alfa, damactocog alfa pegol and turoctocog alfa pegol after a single i.v. injection, PK assessments will be based on FVIII activity levels determined by one-stage clotting assay, up to 7 days and 14 days after the administration of the respective drugs.
Secondary Outcome Measures: 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., The area under the curve will be calculated based on drug concentration analyses from time zero to last quantifiable sample collection timepoint, up to 7 days and 14 days after the administration of the respective drugs.|To characterize Cmax of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Maximum concentration observed (Cmax) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To characterize clearance of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Clearance of drug/s (CL) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To characterize volume of distribution of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Volume of distribution (Vd) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To characterize mean residence time of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Mean residence time (MRT) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To characterize incremental recovery of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Incremental Recovery (IR) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To characterize time to specific plasma FVIII levels of efanesoctocog alfa and damoctocog alfa pegol or turoctocog alfa pegol after a single IV injection., Time to specific plasma FVIII:C levels (40%, 20%, and 10%) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|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., Time to spent in plasma FVIII:C normal range (50% - 150%) assessed by FVIII activity measurement by one-stage aPTT clotting assay, up to 7 days and 14 days after the administration of the respective drugs.|To evaluate the safety and tolerability of a single IV injection of efanesoctocog alfa., 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., From first dose of comparator to end of study, approximately 1 month.