- to evaluate the FVIIa activity PK of 2 CSL689 dose levels in subjects with congenital FVII deficiency- to determine the PK characteristics of FVIIa activity of CSL689- to evaluate the safety and tolerability of intravenous administration of CSL689…
ID
Source
Brief title
Condition
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Elimination half-life of plasma factor VIIa activity
- Maximum observed plasma FVIIa activity
- Area under the curve (AUC0-t), Area under plasma factor VIIa activity versus
time curve from time 0 to last sample with quantifiable activity
Secondary outcome
- Total clearance, Total clearance of plasma factor VIIa activity
- AUC(0-inf), Area under plasma factor VIIa activity versus time curve from
time 0 extrapolated to infinity
- Incremental recovery, Incremental recovery of plasma factor VIIa activity
- Time of occurrence of maximum observed plasma FVIIa activity
- Number of subjects with antibodies against CSL689
- Number of subjects with inhibitors against CSL689
Background summary
Investigating PK, safety and tolerability of CSL689 (rVIIa-FP) in patients with
congenital Factor VII deficiency
Study objective
- to evaluate the FVIIa activity PK of 2 CSL689 dose levels in subjects with
congenital FVII deficiency
- to determine the PK characteristics of FVIIa activity of CSL689
- to evaluate the safety and tolerability of intravenous administration of
CSL689
Study design
A multicenter, randomized, open-label, parallel-arm, phase 1 study to
investigate the PK of CSL689 in subjects with congenital FVII deficiency.
Intervention
Single dose of either NovoSeven (25 µg/kg) or pdFVII (30 IU/kg) and
Single dose of CSL689 (100 or 300 µg/kg)
Study burden and risks
On Day 1, eligible subjects will receive a single dose of their routine
replacement therapy (either NovoSeven rFVIIa [25 µg/kg] or pdFVII [30 IU/kg]),
followed by up to 48 hr of blood sampling for PK assessments. After a washout
period of >= 48 hr, subjects will be randomized to a single dose of 100 µg/kg of
CSL689 or a single dose of 300 µg/kg of CSL689, followed by blood sampling for
PK assessments (0 to 48 hr after administration of CSL689). Routine safety data
will be collected during the study, with follow-up visits to assess potential
formation of inhibitory antibodies.
Based on data from the nonclinical safety pharmacology and toxicity studies,
potential risks associated with CSL689 include the development of anti drug
antibodies and thromboembolic complications. Although considered unlikely
based on evidence from the published literature, there is also a very low risk
of patients with congenital FVII deficiency developing inhibitory antibodies
against CSL689, after treatment with the replacement factor.
None of these risks were observed in the first in human study that included 30
subjects exposed to CSL689 at doses greater than those proposed for the current
study (ranging 140 to 1000 µg/kg bodyweight).
Nonclinical studies, as well as the first in human study (CSL689_1001) have
shown that CSL689 has a favorable PK profile when compared to the currently
available products. As such, the use of a replacement factor with an extended
t1/2 compared to currently available FVIIa products should provide the benefit
of longer intervals between administration of treatment for patients with
congenital FVII deficiency.
However, study CSL689_1001 involved healthy volunteers, and whilst the
collected PK data can be considered as representative of the CSL689 PK profile
in patients with hemophilia, this extrapolation cannot be extended to patients
with congenital FVII deficiency, hence the need for the current PK study.
The characterization of the CSL689 PK profile from the current study will
support further clinical development of CSL689 as replacement therapy for the
treatment of acute bleeding events and for prophylaxis, Given its extended
t1/2, CSL689 is expected to present the possibility of less frequent
treatments, with a resulting positive impact on treatment compliance and a
reduced burden on patients and physicians.
The associated benefit risk balance of the study is considered acceptable for
the enrolled subjects.
Emil-von-Behring-Str. 76
Marburg 35041
DE
Emil-von-Behring-Str. 76
Marburg 35041
DE
Listed location countries
Age
Inclusion criteria
- subjects with proven congenital factor VII deficiency
- age >= 18 years.
- FVII level < 2%.
- minimum of 50 previous exposure days to plasma-derived factor VII or
recombinant factor VIIa
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 or scheduled major and / or orthopedic surgery during the study.
- 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]
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002982-32-NL |
| CCMO | NL51207.091.14 |