TY - JOUR
T1 - Efficacy and safety of rVIII-Singlechain
T2 - Results of a phase 1/3 multicenter clinical trial in severe hemophilia A
AU - Mahlangu, Johnny
AU - Kuliczkowski, Kazimierz
AU - Karim, Faraizah Abdul
AU - Stasyshyn, Oleksandra
AU - Kosinova, Marina V.
AU - Lepatan, Lynda Mae
AU - Skotnicki, Aleksander
AU - Boggio, Lisa N.
AU - Klamroth, Robert
AU - Oldenburg, Johannes
AU - Hellmann, Andrzej
AU - Santagostino, Elena
AU - Baker, Ross I.
AU - Fischer, Kathelijn
AU - Gill, Joan C.
AU - P'Ng, Stephanie
AU - Chowdary, Pratima
AU - Escobar, Miguel A.
AU - Khayat, Claudia Djambas
AU - Rusen, Luminita
AU - Bensen-Kennedy, Debra
AU - Blackman, Nicole
AU - Limsakun, Tharin
AU - Veldman, Alex
AU - Ledger, Katie St
AU - Pabinger, Ingrid
PY - 2016/8/4
Y1 - 2016/8/4
N2 - Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.
AB - Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.
UR - http://www.scopus.com/inward/record.url?scp=84980729305&partnerID=8YFLogxK
U2 - 10.1182/blood-2016-01-687434
DO - 10.1182/blood-2016-01-687434
M3 - Article
C2 - 27330001
AN - SCOPUS:84980729305
SN - 0006-4971
VL - 128
SP - 630
EP - 637
JO - Blood
JF - Blood
IS - 5
ER -