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Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency

Primary Purpose

Congenital Coagulation Factor VII Deficiency

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Eptacog alfa (activated) or pdFVII

CSL689

About this trial

This is an interventional other trial for Congenital Coagulation Factor VII Deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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])

Sites / Locations

Site Reference 5280023
Site Reference # 5780001

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Low-dose CSL689

High-dose CSL689

Arm Description

Single dose of subject's routine FVII replacement therapy (either eptacog alfa [activated] [ie, comparator drug 1] or pdFVII [ie, comparator drug 2]), followed by a single dose of CSL689 at the low dose

Outcomes

Primary Outcome Measures

Terminal half-life of plasma FVIIa activity

Maximum observed plasma FVIIa activity

Area under the curve (AUC0-t)

Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity

Secondary Outcome Measures

Total clearance

Total clearance of plasma FVIIa activity

Volume of distribution of the terminal phase

AUC(0-inf)

Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity

Incremental recovery

Incremental recovery of plasma FVIIa activity

Time of occurrence of maximum observed plasma FVIIa activity

Number of subjects with antibodies against Chinese hamster ovary protein and FVII

Number of subjects with inhibitors against FVII

Full Information

NCT ID

NCT02470871

First Posted

June 10, 2015

Last Updated

April 25, 2017

Sponsor

CSL Behring

1. Study Identification

Unique Protocol Identification Number

NCT02470871

Brief Title

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

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

July 2015 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CSL Behring

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Coagulation Factor VII Deficiency

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low-dose CSL689

Arm Type

Experimental

Arm Description

Arm Title

High-dose CSL689

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Eptacog alfa (activated) or pdFVII

Intervention Description

Comparator Drug 1: Recombinant activated FVII (rFVIIa). Subjects with eptacog alfa (activated) as their routine FVII replacement therapy will receive a single dose of eptacog alfa (activated) in the study. Comparator Drug 2: Plasma-derived FVII (pdFVII). Subjects with pdFVII as their routine FVII replacement therapy will receive a single injection of pdFVII in the study.

Intervention Type

Biological

Intervention Name(s)

CSL689

Intervention Description

Experimental Drug: Recombinant fusion protein, linking activated FVII with albumin (rVIIa-FP). Subjects will receive a single dose of CSL689 at either a low dose (Arm 1) or a high dose (Arm 2)

Primary Outcome Measure Information:

Title

Terminal half-life of plasma FVIIa activity

Time Frame

Up to 48 hours after CSL689 injection

Title

Maximum observed plasma FVIIa activity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

Area under the curve (AUC0-t)

Description

Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Secondary Outcome Measure Information:

Title

Total clearance

Description

Total clearance of plasma FVIIa activity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

Volume of distribution of the terminal phase

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

AUC(0-inf)

Description

Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

Incremental recovery

Description

Incremental recovery of plasma FVIIa activity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

Time of occurrence of maximum observed plasma FVIIa activity

Time Frame

Before injection and at up to 9 time points until 48 hours after injection

Title

Number of subjects with antibodies against Chinese hamster ovary protein and FVII

Time Frame

Up to 30 days after CSL689 injection

Title

Number of subjects with inhibitors against FVII

Time Frame

Up to 30 days after CSL689 injection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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])

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alex Veldman

Organizational Affiliation

CSL Behring

Official's Role

Study Director

Facility Information:

Facility Name

Site Reference 5280023

City

Njmegen

ZIP/Postal Code

6500

Country

Netherlands

Facility Name

Site Reference # 5780001

City

Oslo

ZIP/Postal Code

0372

Country

Norway

12. IPD Sharing Statement

Learn more about this trial

Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency

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