Aleksander Skotnicki1, Toshko J Lissitchkov2, Vasily Mamonov3, Evgeny Buevich4, Kazimierz Kuliczkowski5, Stefcho Goranov6, Janusz Kłoczko7, Anna Klukowska8, Svetlana Stankovic9, Liana Gercheva10, Tatiana Chernova11, Andrzej Hellmann12, Anna Dmoszyńska13, Krystyna Zawilska14, Alex Veldman15, Christine Joch15, Wilfried Seifert15. 1. Department of Haematology, Krakow University Hospital, Krakow, Poland. Electronic address: alekskot@cm-uj.krakow.pl. 2. Specialized Hospital for Active Treatment (SHAT) 'Joan Pavel', Sofia, Bulgaria. 3. Russian National Hematology Research Center, Moscow, Russian Federation. 4. GOUVPO Altaysky State Medical University of Roszdrav, Barnaul, Russian Federation. 5. Independent Public Clinical Hospital No. 1, Wroclaw, Poland. 6. UMHAT 'Sveti Georgi', Plovdiv, Bulgaria. 7. Department of Hematology, Medical University of Bialystok, Bialystok, Poland. 8. Department of Pediatrics, Hematology and Oncology of Warsaw Medical University, Warsaw, Poland. 9. University Clinic of Hematology, Skopje, Macedonia. 10. MHAT 'Sveta Marina', Varna, Bulgaria. 11. FGU Kirov Scientific Research Institute of Hematology and Blood Transfusion, Kirov, Russian Federation. 12. Department of Hematology, Medical University of Gdańsk, Gdańsk, Poland. 13. Independent Public Clinical Hospital No. 1, Lublin, Poland. 14. Dept. of Hematology, J. Strus Hospital, Poznan, Poland. 15. CSL Behring, Clinical Research & Development, Marburg, Germany.
Abstract
INTRODUCTION:VONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate,which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and aVWF/factor VIII (FVIII) ratio of ~2.4:1, similar to Haemate® P (CSL Behring). METHODS: The pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre,double-blind, randomised study. Subjects aged ≥ 12 years with haemophilia A who required treatment of nonsurgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokinetics were investigated with a single dose of 50 IU FVIII/kg body weight of either VONCENTO® or BIOSTATE® reference product (Biostate-RP) (Day 1; Day 8 [n= 16], repeated on Day 180 [VONCENTO® only; n=15]). Efficacy and safety analyses were performed either during on-demand treatment (n=52) or prophylaxis (n=29)for ≥ 6 months and ≥ 50 exposure days, respectively. RESULTS: Besides the confirmation of bioequivalence between VONCENTO® and Biostate-RP, which displayed comparable PK profiles, haemostatic efficacy was rated by the investigators as either 'excellent' or 'good' in 96.4% of all bleeding events (96.5% spontaneous, 96.6% traumatic, 96.9% joint bleeds) as well as in 80% of major and 100% of minor surgical procedures at discharge. The median number of annualised bleeding events per subject [range] was significantly lower in the prophylaxis group (2.0 [0.0-34.6]) than in the on-demand group (14.0 [0.0-87.8], p = 0.0013).VONCENTO® was well tolerated and no inhibitory antibodies were identified during the study period. CONCLUSIONS: This study demonstrated the bioequivalence of VONCENTO® to Biostate-RP, and its excellent efficacy and safety profile in haemophilia A subjects.
RCT Entities:
INTRODUCTION: VONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate,which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and aVWF/factor VIII (FVIII) ratio of ~2.4:1, similar to Haemate® P (CSL Behring). METHODS: The pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre,double-blind, randomised study. Subjects aged ≥ 12 years with haemophilia A who required treatment of nonsurgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokinetics were investigated with a single dose of 50 IU FVIII/kg body weight of either VONCENTO® or BIOSTATE® reference product (Biostate-RP) (Day 1; Day 8 [n= 16], repeated on Day 180 [VONCENTO® only; n=15]). Efficacy and safety analyses were performed either during on-demand treatment (n=52) or prophylaxis (n=29)for ≥ 6 months and ≥ 50 exposure days, respectively. RESULTS: Besides the confirmation of bioequivalence between VONCENTO® and Biostate-RP, which displayed comparable PK profiles, haemostatic efficacy was rated by the investigators as either 'excellent' or 'good' in 96.4% of all bleeding events (96.5% spontaneous, 96.6% traumatic, 96.9% joint bleeds) as well as in 80% of major and 100% of minor surgical procedures at discharge. The median number of annualised bleeding events per subject [range] was significantly lower in the prophylaxis group (2.0 [0.0-34.6]) than in the on-demand group (14.0 [0.0-87.8], p = 0.0013).VONCENTO® was well tolerated and no inhibitory antibodies were identified during the study period. CONCLUSIONS: This study demonstrated the bioequivalence of VONCENTO® to Biostate-RP, and its excellent efficacy and safety profile in haemophilia A subjects.