40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics, and preliminary efficacy in hemophilia patients with inhibitors.
Ljung, Rolf LU
; Karim, F A
; Saxena, K
; Suzuki, Toru
LU
; Arkhammar, P
; Rosholm, A
and Giangrande, P
(2013)
In Journal of Thrombosis and Haemostasis
11(7).
p.1260-1268
- Abstract
- BACKGROUND: A 40K glycoPEGylated, recombinant Factor VIIa (rFVIIa) bypassing agent (N7-GP) with a prolonged half-life (15 h) compared to rFVIIa was developed as a potential candidate for bleed preventive regimens in patients with hemophilia and inhibitors. OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of multiple doses of N7-GP in congenital hemophilia A and B patients with high-titer inhibitors. PATIENTS/METHODS: In this global, prospective, randomized, double-blinded, phase 2 trial, 25, 100, or 200 μg kg(-1) N7-GP was administered intravenously once every second day during a 3-month bleed preventive regimen and compared with a preceding 3-month observation period with on-demand treatment of bleeds with... (More)
- BACKGROUND: A 40K glycoPEGylated, recombinant Factor VIIa (rFVIIa) bypassing agent (N7-GP) with a prolonged half-life (15 h) compared to rFVIIa was developed as a potential candidate for bleed preventive regimens in patients with hemophilia and inhibitors. OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of multiple doses of N7-GP in congenital hemophilia A and B patients with high-titer inhibitors. PATIENTS/METHODS: In this global, prospective, randomized, double-blinded, phase 2 trial, 25, 100, or 200 μg kg(-1) N7-GP was administered intravenously once every second day during a 3-month bleed preventive regimen and compared with a preceding 3-month observation period with on-demand treatment of bleeds with rFVIIa. The primary endpoint was adverse events; secondary endpoints were evaluation of immunogenicity, pharmacokinetics, and efficacy. RESULTS AND CONCLUSIONS: Overall, 23 patients were randomized and dosed (n = 8/7/8 for 25/100/200 μg kg(-1) ). N7-GP was well tolerated, with a low frequency of adverse events. No serious adverse events, immunogenic or thromboembolic events related to N7-GP were reported. The pharmacokinetic properties of N7-GP were similar to those reported in phase 1. The annualized bleeding rate (ABR) decreased in the treatment period vs. the observation period at all N7-GP dose levels. However, a dose-response relationship in the reduction could not be established in the N7-GP dose range evaluated. The ABR was also reduced at two dose levels during the last part of the observation period, and increased notably in the follow-up period irrespective of previous N7-GP dose. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00951405). This article is protected by copyright. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3733870
- author
- Ljung, Rolf
LU
; Karim, F A
; Saxena, K
; Suzuki, Toru
LU
; Arkhammar, P
; Rosholm, A
and Giangrande, P
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Thrombosis and Haemostasis
- volume
- 11
- issue
- 7
- pages
- 1260 - 1268
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000321763500006
- pmid:23578227
- scopus:84880198215
- pmid:23578227
- ISSN
- 1538-7933
- DOI
- 10.1111/jth.12237
- language
- English
- LU publication?
- yes
- id
- 7762a304-9a42-4058-833c-34bc2380c751 (old id 3733870)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23578227?dopt=Abstract
- date added to LUP
- 2016-04-01 10:40:44
- date last changed
- 2022-01-26 01:24:40
@article{7762a304-9a42-4058-833c-34bc2380c751,
abstract = {{BACKGROUND: A 40K glycoPEGylated, recombinant Factor VIIa (rFVIIa) bypassing agent (N7-GP) with a prolonged half-life (15 h) compared to rFVIIa was developed as a potential candidate for bleed preventive regimens in patients with hemophilia and inhibitors. OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of multiple doses of N7-GP in congenital hemophilia A and B patients with high-titer inhibitors. PATIENTS/METHODS: In this global, prospective, randomized, double-blinded, phase 2 trial, 25, 100, or 200 μg kg(-1) N7-GP was administered intravenously once every second day during a 3-month bleed preventive regimen and compared with a preceding 3-month observation period with on-demand treatment of bleeds with rFVIIa. The primary endpoint was adverse events; secondary endpoints were evaluation of immunogenicity, pharmacokinetics, and efficacy. RESULTS AND CONCLUSIONS: Overall, 23 patients were randomized and dosed (n = 8/7/8 for 25/100/200 μg kg(-1) ). N7-GP was well tolerated, with a low frequency of adverse events. No serious adverse events, immunogenic or thromboembolic events related to N7-GP were reported. The pharmacokinetic properties of N7-GP were similar to those reported in phase 1. The annualized bleeding rate (ABR) decreased in the treatment period vs. the observation period at all N7-GP dose levels. However, a dose-response relationship in the reduction could not be established in the N7-GP dose range evaluated. The ABR was also reduced at two dose levels during the last part of the observation period, and increased notably in the follow-up period irrespective of previous N7-GP dose. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00951405). This article is protected by copyright. All rights reserved.}},
author = {{Ljung, Rolf and Karim, F A and Saxena, K and Suzuki, Toru and Arkhammar, P and Rosholm, A and Giangrande, P}},
issn = {{1538-7933}},
language = {{eng}},
number = {{7}},
pages = {{1260--1268}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Thrombosis and Haemostasis}},
title = {{40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics, and preliminary efficacy in hemophilia patients with inhibitors.}},
url = {{http://dx.doi.org/10.1111/jth.12237}},
doi = {{10.1111/jth.12237}},
volume = {{11}},
year = {{2013}},
}