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Fixed doses of N8‐GP prophylaxis maintain moderate‐to‐mild factor VIII levels in the majority of patients with severe hemophilia A
- Source :
- Research and Practice in Thrombosis and Haemostasis, Vol 3, Iss 3, Pp 542-554 (2019), Research and Practice in Thrombosis and Haemostasis
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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.
- Subjects :
- medicine.medical_specialty
von Willebrand factor
Severe hemophilia A
Recombinant factor viii
Gastroenterology
Von Willebrand factor
Pharmacokinetics
hemic and lymphatic diseases
Internal medicine
medicine
In patient
Dosing
recombinant
Original Articles: Haemostasis
biology
business.industry
lcsh:RC633-647.5
Hematology
lcsh:Diseases of the blood and blood-forming organs
Confidence interval
Online‐only Articles
factor VIII
biology.protein
Original Article
hemophilia A
Previously treated
business
pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 24750379
- Volume :
- 3
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Research and Practice in Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....c27d21935acf7968981101605f013c70