Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study

Haemophilia ◽  
2014 ◽  
Vol 20 (5) ◽  
pp. 651-658 ◽  
Author(s):  
J. Windyga ◽  
T. Lissitchkov ◽  
O. Stasyshyn ◽  
V. Mamonov ◽  
H. Ghandehari ◽  
...  
Keyword(s):  
Factor Ix ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Invasive Procedures ◽  
Open Label ◽  
Multicentre Phase ◽  
Recombinant Factor Ix ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated

A Pharmacokinetic Study of the Plasma-Derived Factor IX AlphaNine® and Its Comparison with the Recombinant Factor IX BeneFIX®, in Previously Treated Patients with Severe Hereditary Hemophilia B.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3955-3955
Author(s):  
Vicente R. Cortina ◽  
T. Lissichkov ◽  
K. Zavilska ◽  
M. Matysiak ◽  
L. Gercheva ◽  
...  
Keyword(s):  
Half Life ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Haemophilia ◽  
Open Label ◽  
Recombinant Factor Ix ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
In Vivo Recovery

Abstract Objectives The objective of the present study was two fold: first, to determine the pharmacokinetic (PK) profile of the plasma-derived FIX concentrate AlphaNine® in patients with congenital severe haemophilia B (FIX:C 2%). To do this, two PK studies were carried out one six months after the first. The second objective was a comparison of the Alphanine® PK profile with the recombinant Factor IX, BeneFIX®. Patients and methods The first study was a prospective, five-center, open-label, comparative, PK study carried out in 25 severe hemophilia B patients who received 2 single doses of 65–75 IU/kg of AlphaNine® within 6 months (t=0 and t=6). The following parameters were assessed: in vivo recovery, half-life, AUC, mean residence time and clearance. As an extension of the study, a single dose of 65–75 IU/kg of BeneFIX® was administered in 9 out of 25 patients, after a wash-out period of 7–15 days. Results Table 1 summarizes the results obtained when comparing AlphaNine® within a period of time of 6 months (PK1 vs PK2) in 25 patients. Table 2 shows the results obtained when comparing the in vivo recovery of AlphaNine ® vs BeneFIX ® in the 9 patients studied. Conclusions These results confirm that AlphaNine® PK has similar profile as other plasma derived FIX products presently available to treat Hemophilia B patients. In addition, our results show that the recombinant FIX studied, BeneFIX® has a reduced in vivo recovery when is compared to AlphaNine®. Table 1 Parameter AlphaNine® (PK1) t=0 m AlphaNine® (PK2) t=6 m Results are expressed as Mean (SD) In vivo recovery (IU/dl:IU/kg) 1.0 (0.2) 1.2 (0.4) Half-life (h) 34.5 (6.2) 33.7 (5.4) Clearance (ml/min) 0.07 (0.01) 0.07 (0.01) AUC0-inf (IUxh/dl) 1602 (312) 1644 (360) MRT0-inf (h) 35.8 (5.4) 34.6 (5.2) Table 2 Parameter AlphaNine® (PK2) BeneFIX® Results are expressed as Mean (SD); * p<0.05 for the comparison of the in vivo recovery for the BeneFIX® group with the AlphaNine® PK2 In vivo recovery (IU/dl:IU/kg) 1.3 (0.5) 0.8 (0.2)*

scholarly journals Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B

2020 ◽  
Vol 120 (05) ◽  
pp. 737-746
Author(s):  
Manuel Carcao ◽  
Susan Kearney ◽  
Meng Yao Lu ◽  
Masashi Taki ◽  
Daniel Rubens ◽  
...  
Keyword(s):  
Factor Ix ◽  
Hemophilia B ◽  
Phase Iii ◽  
Open Label ◽  
Safety And Efficacy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Inhibitory Antibodies

AbstractLong-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ≤ 12 years with HB (FIX activity ≤ 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (≥ 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ≥ 5 years' follow-up) and compare with a 1-year analysis (≥ 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ≥ 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ≤ 2%).

Molecular marker assessments for epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) and histoscore (H-score) in the phase III SELECT trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8052-8052
Author(s):  
Edward S. Kim ◽  
Sreenivas Chittoor ◽  
Craig H. Reynolds ◽  
Lorinda Simms ◽  
Scott Saxman
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Phase Iii ◽  
Egfr Expression ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Epidermal Growth ◽  
Select Trial

8052 Background: SELECT was a phase III study that investigated whether the addition of cetuximab (C) to pemetrexed (P) improved outcome in previously treated patients (pts) with recurrent or progressive non-small cell lung cancer (NSCLC). Clinical results have been reported previously and demonstrated that adding C to P did not improve progression-free survival (PFS) or overall survival (OS). H-score has been reported to be a potential predictor of outcome for C therapy. Prespecified biomarker analyses, including EGFR IHC and H-score, are reported here. Methods: EGFRexpression in tumor tissue was not required for eligibility; however, tissue was collected and analyzed for EGFR expression by IHC using standard methods. In addition, H-score evaluation was performed by trained central pathologists and correlated with clinical outcome using a predefined cutoff for “low” and “high” of <200 and ≥200, respectively. Results: A total of 449 (IHC) and 406 (H-score) pt specimens were evaluable. Demographics for pts with tissue available for EGFR analysis were similar to the overall population. For IHC+ pts (n=396), median PFS for C+P was 3.02 months (95% CI, 2.76–3.45) compared with 2.99 months (95% CI, 2.63–4.14) for P (HR, 1.02 [95% CI, 0.83–1.24]; p=.86). For pts with low H-score (N=99 [C+P] and N=111 [P]), median PFS was 2.7 months (95% CI, 1.8–3.2) with C+P and 3.1 months (95% CI, 2.6–4.1) with P (HR, 1.11 [95% CI, 0.84–1.46]; P=.48); median OS was 6.7 months (95% CI, 5.3–8.6) with C+P and 6.6 months (95% CI, 4.7–9.2) with P (HR, 0.96 [95% CI, 0.72–1.27]; P=.76). Among pts with high H-scores (N=101 [C+P] and N= 95 [P]), median PFS was 3.2 months (95% CI, 2.7–4.6) with C+P and 3.7 months (95% CI, 1.7–4.5) with P (HR, 1.02 [95% CI, 0.77–1.37]; P=.86); median OS was 7.7 months (95% CI, 6.5–10.9) with C+P and 8.0 months (95% CI, 7.0–9.1) with P (HR, 1.17 [95% CI, 0.86–1.57]; P=.32). Conclusions: EGFR H-score was not predictive of benefit for the addition of C to P in this population of pts with NSCLC. There was also no treatment effect in the IHC+ group. Clinical trial information: NCT00095199.

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