Journal article
Fixed doses of N8‐GP prophylaxis maintain moderate‐to‐mild factor VIII levels in the majority of patients with severe hemophilia A
Research and practice in thrombosis and haemostasis, Vol.3(3), pp.542-554
07/2019
DOI: 10.1002/rth2.12220
PMCID: PMC6611478
PMID: 31294338
Abstract
Background
N8‐GP is an extended half‐life recombinant factor VIII developed for prophylaxis and treatment of bleeds in patients with hemophilia A.
Objective
To assess pharmacokinetic (PK) characteristics of N8‐GP in previously treated patients with severe hemophilia A, model the time spent at hemophilia thresholds of ≥1 and ≤5 IU/dL (moderate) or >5 IU/dL (mild) FVIII levels during N8‐GP prophylaxis, and investigate the relationship between N8‐GP half‐life and von Willebrand factor (vWF).
Methods
PK assessments were obtained from patients with severe hemophilia A (FVIII < 1 IU/dL) participating in 4 clinical trials: pathfinder 1 (20‐60 years); pathfinder 2 (12‐17 and ≥18 years); pathfinder 5 (0‐11 years), and pathfinder 7 (25‐71 years). All PK profiles were assessed after washout and considered single‐dose PK profiles. Pre‐ and postdose FVIII activity at steady state was measured at all visits.
Results
From 69 patients, 108 PK profiles of N8‐GP 50 IU/kg were assessed. Adults/adolescents received 50 IU/kg every 4 days, achieving mean trough levels of 3.0 IU/dL (95% confidence interval, 2.6‐3.5, adults) and 2.7 IU/dL (1.8‐4.0, adolescents). Children received 60 IU/kg twice weekly, leading to mean trough levels of 1.2 IU/dL (0.8‐1.6, 0‐ to 5‐year‐olds) and 2.0 IU/dL (1.5‐2.7, 6‐ to 11‐year‐olds). PK modeling predicted children dosed every 3 days and adults/adolescents dosed every 3 to 4 days would maintain FVIII levels >5 and >1 IU/dL for >80% and 100% of the time, respectively. N8‐GP half‐life correlated linearly with von Willebrand factor levels in adults/adolescents, less in children.
Conclusions
Prophylaxis with fixed intervals (Q4D/twice weekly) and fixed weight‐based dosing (50/60 IU/kg) ensured >1 IU/dL FVIII trough levels in both adults and children.
Details
- Title: Subtitle
- Fixed doses of N8‐GP prophylaxis maintain moderate‐to‐mild factor VIII levels in the majority of patients with severe hemophilia A
- Creators
- Pratima Chowdary - The Royal Free HospitalManuel Carcao - University of TorontoPål A. Holme - Oslo University HospitalVictor Jiménez‐Yuste - Autonoma UniversitySteven R. Lentz - Roy J. and Lucille A. Carver College of MedicineJudi Møss - Novo NordiskLone H. Poulsen - Aarhus University HospitalChunduo Shen - Novo NordiskAlberto Tosetto - Ospedale San BortoloAllison Wheeler - Vanderbilt UniversityElena Santagostino - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Resource Type
- Journal article
- Publication Details
- Research and practice in thrombosis and haemostasis, Vol.3(3), pp.542-554
- DOI
- 10.1002/rth2.12220
- PMID
- 31294338
- PMCID
- PMC6611478
- ISSN
- 2475-0379
- eISSN
- 2475-0379
- Number of pages
- 13
- Grant note
- Novo Nordisk A/S (Bagsværd, Denmark)
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360147402771
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