Clinical trial NCT02470871: Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency
Official title: Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Congenital Coagulation Factor VII Deficiency
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2015-06-12
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to investigate the pharmacokinetics (PK) and safety of rVIIa-FP (CSL689) in a total of 10 to 16 male or female adults with inherited coagulation factor VII (FVII) deficiency. Subjects will receive a single dose of their routine FVII replacement product (ie, either recombinant activated coagulation FVII \[rFVIIa, eptacog alfa (activated)\] or plasma-derived FVII \[pdFVII\]) as a comparator, and will then be randomly assigned to a single low dose or a single high dose of the study product CSL689 (8 subjects per CSL689 dose level). Serial blood samples for PK analysis will be taken up to 24 hours after the eptacog alfa (activated) or pdFVII injection, and up to 48 hours after the CSL689 injection. Subject safety will be routinely monitored throughout the study.


Eligibility criteria: Inclusion Criteria:

* Proven congenital FVII deficiency.
* Age ≥ 18 years.
* FVII level \< 2% of normal levels.
* Minimum of 50 previous exposure days to pdFVII (including prothrombin complex concentrates \[PCCs\]) or rFVIIa.

Exclusion Criteria:

* History of, or risk factors for, thromboembolic events, including known deep vein thrombosis.
* Inhibitor to FVII or rFVIIa, current or historic.
* Known or suspected hypersensitivity to hamster protein, to CSL689, or to any excipient of CSL689.
* Known or suspected allergy to rFVIIa or hamster protein.
* Major surgery within 1 month before screening.
* Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
* Human immunodeficiency virus (HIV)-positive subjects with cluster of differentiation 4 (CD4)+ lymphocyte count of \< 200/µL at screening.
* Use of an investigational agent within 30 days before the study.
* Use of concomitant therapy not permitted during the study (ie, other platelet inhibitors, desmopressin, fibrinolysis inhibitors, except if used as local treatment \[eg, for oral bleeds\])

Primary outcomes:
measure: Terminal half-life of plasma FVIIa activity
timeFrame: Up to 48 hours after CSL689 injection
measure: Maximum observed plasma FVIIa activity
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: Area under the curve (AUC0-t)
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
Secondary outcomes:
measure: Total clearance
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: Volume of distribution of the terminal phase
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: AUC(0-inf)
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: Incremental recovery
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: Time of occurrence of maximum observed plasma FVIIa activity
timeFrame: Before injection and at up to 9 time points until 48 hours after injection
measure: Number of subjects with antibodies against Chinese hamster ovary protein and FVII
timeFrame: Up to 30 days after CSL689 injection
measure: Number of subjects with inhibitors against FVII
timeFrame: Up to 30 days after CSL689 injection
Other outcomes:
Locations:
city: Njmegen
country: Netherlands
facility: Site Reference 5280023
city: Oslo
country: Norway
facility: Site Reference # 5780001
Study officials:
affiliation: CSL Behring
name: Alex Veldman
role: STUDY_DIRECTOR
References: