Dataset Information

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

ABSTRACT: BACKGROUND:BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. OBJECTIVES:To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. PATIENTS/METHODS:This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ? 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ? 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg?1; cohort 2 [n = 7], 50 IU kg?1) for a 48-h pharmacokinetic (PK) study. After another ? 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg?1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg?1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. RESULTS:BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. CONCLUSIONS:This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

SUBMITTER: Coyle TE

PROVIDER: S-EPMC4265842 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

Coyle T E TE Reding M T MT Lin J C JC Michaels L A LA Shah A A Powell J J

Journal of thrombosis and haemostasis : JTH 20140401 4

<h4>Background</h4>BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia.<h4>Objectives</h4>To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A.<h4>Patients/methods</h4>This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years w ...[more]

PMID: 24843882

Similar Datasets

Project description:IntroductionBAY 94-9027 is a newly developed extended half-life product to treat haemophilia, allowing for fewer injections than with standard products. This post hoc analysis aimed to compare physicians' and patients' opinions on BAY 94-9027 prophylaxis, and explore how qualitative interview data is aligned with the data from the Haemophilia-specific Quality of Life questionnaire for Adults (Haemo-QoL-A).MethodsExploratory qualitative interviews were conducted with physicians and patients by phone upon the exit of patients from the PROTECT VIII extension phase following a semi-directed guide. In this post hoc analysis, all transcripts were reviewed and reported concepts were compared to assess the level of concordance between physicians and patients. These qualitative data were compared with the Haemo-QoL-A mean global and subscale scores at baseline and end of main phase (36 weeks later).ResultsTen physicians and 16 patients (mean age 47 years) from Israel, the Netherlands and the USA were interviewed. Significant improvements were reported by all physicians from baseline [e.g. lower frequency of bleeds (80%), improvement in emotional functioning (90%)], which is in concordance with patients' reports. The improved confidence reported by physicians cascaded to greater participation in various activities, resulting in a better perceived emotional state and a significant improvement on the Haemo-QoL-A emotional impact subscale score (p = 0.04) between baseline and end of main phase. Most physicians (80%) reported improvement in bleed frequency, as patients did (88%). Improvement in physical functioning or mobility was not consistently reported in this 8-month study.ConclusionInterviewed physicians and patients generally agreed on the beneficial impact of BAY 94-9027, specifically regarding the increased level of self-confidence in patients and its subsequent positive impact on patients' lives. These findings supported the observed improvement on the Haemo-QoL-A emotional impact subscale. Overall, this study highlights the concordance between physician and patient perspective on the positive experience with BAY 94-9027.

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.

Dataset Information

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

Publications

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets