Abstract
Current factor IX (FIX) products display a half-life (t 1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG 1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t 1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 666-672 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 119 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 19 2012 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. / Shapiro, Amy D.; Ragni, Margaret V.; Valentino, Leonard A.; Key, Nigel S.; Josephson, Neil C.; Powell, Jerry S; Cheng, Gregory; Thompson, Arthur R.; Goyal, Jaya; Tubridy, Karen L.; Peters, Robert T.; Dumont, Jennifer A.; Euwart, Donald; Li, Lian; Hallén, Bengt; Gozzi, Peter; Bitonti, Alan J.; Jiang, Haiyan; Luk, Alvin; Pierce, Glenn F.
In: Blood, Vol. 119, No. 3, 19.01.2012, p. 666-672.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients
AU - Shapiro, Amy D.
AU - Ragni, Margaret V.
AU - Valentino, Leonard A.
AU - Key, Nigel S.
AU - Josephson, Neil C.
AU - Powell, Jerry S
AU - Cheng, Gregory
AU - Thompson, Arthur R.
AU - Goyal, Jaya
AU - Tubridy, Karen L.
AU - Peters, Robert T.
AU - Dumont, Jennifer A.
AU - Euwart, Donald
AU - Li, Lian
AU - Hallén, Bengt
AU - Gozzi, Peter
AU - Bitonti, Alan J.
AU - Jiang, Haiyan
AU - Luk, Alvin
AU - Pierce, Glenn F.
PY - 2012/1/19
Y1 - 2012/1/19
N2 - Current factor IX (FIX) products display a half-life (t 1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG 1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t 1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.
AB - Current factor IX (FIX) products display a half-life (t 1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG 1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t 1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.
UR - http://www.scopus.com/inward/record.url?scp=84862908041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862908041&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-07-367003
DO - 10.1182/blood-2011-07-367003
M3 - Article
C2 - 22110246
AN - SCOPUS:84862908041
VL - 119
SP - 666
EP - 672
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -