Dataset Information

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A.

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.

SUBMITTER: Chowdary P

PROVIDER: S-EPMC6611478 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A.

Chowdary Pratima P Carcao Manuel M Holme Pål A PA Jiménez-Yuste Victor V Lentz Steven R SR Møss Judi J Poulsen Lone H LH Shen Chunduo C Tosetto Alberto A Wheeler Allison A Santagostino Elena E

Research and practice in thrombosis and haemostasis 20190611 3

<h4>Background</h4>N8-GP is an extended half-life recombinant factor VIII developed for prophylaxis and treatment of bleeds in patients with hemophilia A.<h4>Objective</h4>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 facto ...[more]

PMID: 31294338

Similar Datasets

Project description:BackgroundLow-dose pharmacokinetic (PK)-guided extended half-life (EHL) factor VIII (FVIII) prophylaxis can reduce the bleeding risk in hemophilia A (HA) patients. An increase in physical activities for promoting musculoskeletal health may enhance the benefits of prophylactic therapy.ObjectivesTo determine the clinical impact of moderate- to vigorous-intensity physical activities in HA patients during low-dose PK-guided EHL FVIII prophylaxis.Patients/methodsThis prospective study enrolled patients with moderate/severe HA (baseline FVIII levels ≤ 5 IU/dL) who had received low-dose PK-guided EHL FVIII prophylaxis for ≥ 6 months. An individualized exercise protocol was introduced to each participant, targeting a 65% increase in the maximum predicted heart rate for ≥ 150 min/week, while continuing low-dose PK-guided EHL FVIII prophylaxis for 6 months. Before and after implementing the intervention, annualized bleeding rates (ABR), annualized joint bleeding rates (AJBR), Hemophilia Joint Health Scores (HJHS), skeletal muscle mass, hemophilia-specific quality-of-life (QoL) scores and annualized FVIII consumption were compared.ResultsOf 13 participants (mean age ± standard deviation [SD]: 20.1 ± 6.8 years), ABR, AJBR, and HJHS were significantly reduced (mean differences [MD] ± SD: -5.7 ± 2.6 bleeds/year, -4.2 ± 2.6 joint bleeds/year, and -4.3 ± 3.2 marks, respectively; P < 0.05) after applying the 6-month exercise protocol. Skeletal muscle mass and QoL scores had also improved (P = 0.001), while FVIII usage had decreased (MD ± SD: -129.1 ± 208.7 IU/kg/year; P < 0.05).ConclusionsThe combination of moderate- to vigorous-intensity physical activities with low-dose PK-guided EHL FVIII prophylaxis improves bleeding prevention, musculoskeletal status and QoL in patients with moderate/severe HA. By minimizing FVIII consumption, this strategy helps optimize hemophilia care in countries with budget constraints.Clinicaltrialsgov NCT05728528.

Project description:PurposeTo illustrate the benefits of the extended half-life (EHL) recombinant factor VIII product N8-GP (Esperoct®, turoctocog alfa pegol) by describing individual cases of patients with severe hemophilia A treated with N8-GP in the pathfinder clinical trial program.Patients and methodsThis manuscript presents selected patient cases from the pivotal pathfinder clinical trial program, which included a number of clinical studies in adults (pathfinder 2 and 3) and children (pathfinder 5); overall results published previously. Clinical data and outcomes described in this manuscript are more detailed and derived from several interesting patient cases (five adults from pathfinder 2 and two children from pathfinder 5), who received N8-GP as prophylaxis (PPX) for their severe hemophilia A. Three of the five adults described here also underwent multiple major surgeries (for which they moved from pathfinder 2 into pathfinder 3 and later returned to pathfinder 2). New analyses on pediatric joint health from pathfinder 5 are also summarized here. Outcomes assessed included bleeding complications, improvements in quality of life, intraoperative hemostatic response, blood loss during surgery, number of blood transfusions, and annualized bleeding rates. For the pediatric patients, target joint resolution, adverse events, and annualized joint bleeding rate were also assessed, all by the treating physician.ResultsConsiderable improvements in treatment adherence, bleeding rates, and overall physical activity levels were demonstrated in two adult cases from the pathfinder 2 trial. N8-GP demonstrated good or excellent hemostatic coverage in three adult patients undergoing multiple major surgeries. The benefits of N8-GP for joint health and in support of children and adolescents with evolving active lifestyles were reported for several pediatric cases.ConclusionThese patient cases highlight the benefits of EHL products, such as N8-GP, for patients with severe hemophilia A. They include more challenging scenarios relating to improvements in previously poor adherence to PPX, children with active sporting lifestyles, and patients requiring multiple major surgeries.

Dataset Information

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A.

Publications

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets