Efficacy and safety of rVIII-SingleChain in 21 major surgeries

J. Oldenburg1, C. Djambas Khayat2, J. Mahlangu3, R. Baker4, C. Leissinger5, E. Santagostino6, M. F. Lopez-Fernandez7, F. Abdul Karim8, A. Veldman9, K. St. Ledger10, I. Pabinger11 (1Bonn, Germany, 2Beirut, Lebanon, 3Johannesburg, South Africa, 4Nedlands, Australia, 5New Orleans, United States, 6Milan, Italy, 7La Coruña, Spain, 8Jalan Tun Razak, Kuala Lumpur, Malaysia, 9Marburg, Germany, 10King of Prussia, United States, 11Vienna, Austria)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: rVIII-SingleChain is a novel recombinant Factor VIII with a truncated B-domain and a covalent bond between the heavy and light chain, demonstrating a high binding affinity for von Willebrand factor. In the AFFINITY clinical trial program, the safety and efficacy of rVIII-SingleChain was assessed in pediatric, adolescent and adult patients with severe hemophilia A undergoing surgery.

Methods: The studies were approved by the relevant Ethics committee and national authorities and conducted according to GCP and the Declaration of Helsinki. Patients undergoing major surgery (defined as a surgical procedure that required general, spinal or regional anesthesia) were given rVIII-SingleChain as a bolus or continuous infusion. Dosing was guided by WFH recommendations. The efficacy of rVIII-SingleChain in surgical prophylaxis was rated by the investigator based on information by the surgeon on intraoperative hemostasis, using a 4-point rating scale. Treatments assigned an efficacy rating of “excellent” (defined as hemostasis not clinically significant different from normal) or “good” (defined as hemostasis normal or mildly abnormal in terms of quantity and/or quality e.g., slight oozing) were considered successful.

Results: A total of 21 surgeries were performed in 18 patients: extraction of multiple teeth (2), abdominal hernia repair, elbow replacement, ankle arthroplasty, knee replacement (5), knee arthroscopy, cholecystectomy, lengthening of the Achilles tendon combined with straighten up of the right toes, circumcision (5), excision, curettage and bone grafting of radius/ulnar pseudo tumor, open reduction internal fixation right ankle fracture and hardware removal right ankle. Of these 21 surgeries, a significant number carried a high risk of bleeding, among these were 10 orthopedic surgeries. A total of 13 surgeries were performed with a single bolus of rVIII-SingleChain; 8 were performed with continuous infusion. Investigators rated the hemostatic efficacy of rVIII-SingleChain during surgery as “excellent” (n=19) or “good” (n=2) in all cases. No related adverse events or serious adverse events were observed during the surgery period.

Conclusion: rVIII-SingleChain demonstrated effective hemostatic control and a good safety profile during major surgery when dosed either by continuous infusion or by bolus infusion.