Abstract

Background: rVIII-SingleChain, a novel recombinant Factor VIII, has been designed as a B-domain truncated construct with a covalent bond between the heavy and light chain, aiming for a higher binding affinity to von Willebrand Factor. rVIII-SingleChain has a lower clearance, longer half-life and larger area under the curve compared to octocog alfa (AdvateĀ®). This sub-study of the AFFINITY program investigated the safety and efficacy of rVIII-SingleChain to control hemostasis in adult and adolescent patients (12 - 65 years of age) with severe Hemophilia A undergoing major surgery. rVIII-SingleChain was used either as continuous infusion or as a bolus injection.

Methods: The study was approved by the relevant ethics committees and national authorities and conducted according to GCP and the Declaration of Helsinki. 13 patients underwent a total of 16 major surgical procedures (a surgical procedure that required general, spinal or regional anesthesia). Dosing was guided by the WFH recommendations. In 8 patients, rVIII-SingleChain was used as continuous infusion and in 8 patients rVIII-SingleChain was used as a bolus injection.

Results: The following procedures were performed using continuous infusion: knee replacement (5), cholecystectomy, lengthening of the achilles tendon combined with surgical correction of the right toes, and open reduction and internal fixation of right ankle fracture. Furthermore, circumcision (3), extraction of wisdom teeth, abdominal hernia repair, elbow replacement, ankle arthroplasty, and hardware removal of the right ankle were performed after administering a bolus injection of rVIII-SingleChain. In the 8 procedures that were covered by bolus injection rVIII-SingleChain median pre- and intraoperative consumption was 79.2 IU/kg, and in the 8 procedures that were covered by continuous infusion, rVIII-SingleChain median pre- and intraoperative consumption was 92.5 IU/kg. Investigators rated the efficacy of rVIII-SingleChain during surgery as excellent (defined as hemostasis not clinically significant different from normal) in all cases but one (knee replacement under continuous infusion), in which it was rated as good (defined as hemostasis normal or mildly abnormal in terms of quantity and/or quality e.g., slight oozing). After the procedure, patients returned to routine treatment after a median of 9 days. No related AEs or SAEs were observed during the surgery period.

Conclusion: rVIII-SingleChain provides very effective and safe control of hemostasis during a wide range of surgical procedures when dosed either by continuous infusion or by bolus injection. Consumption of factor on the day of surgery seems to be comparable in both treatment regimens.

Disclosures

Mahlangu:NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Baker:Daiichi Sankyo: Research Funding; CSL Behring: Research Funding; Portola Pharmaceuticals: Research Funding; Astellas: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: conference travel support, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support , Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Other: conference travel support. Leissinger:Biogen: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Santagostino:Pfizer: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Baxter: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Biotest: Speakers Bureau; Octapharma: Speakers Bureau; Kedrion: Speakers Bureau; Biogen/Sobi: Membership on an entity's Board of Directors or advisory committees. Bensen-Kennedy:CSL Behring: Employment. St. Ledger:CSL Behring: Employment. Veldman:CSL Behring: Employment. Pabinger:Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Baxter: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees.

Author notes

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Asterisk with author names denotes non-ASH members.