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CC BY 4.0 · TH Open 2024; 08(03): e273-e282
DOI: 10.1055/s-0044-1787781
Original Article

Reduced Volume and Faster Infusion Rate of Activated Prothrombin Complex Concentrate: A Phase 3b/4 Trial in Adults with Hemophilia A with Inhibitors

Bülent Zülfikar
1   Hereditary Bleeding Disorders Unit in Oncology Institute, Istanbul University, Istanbul, Turkey
,
Johnny Mahlangu
2   Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand and NHLS, Johannesburg, South Africa
,
Salim Mohamed Nekkal
3   CHU Isaad Hassani, Beni Messous, Algiers, Algeria
,
Cecil Ross
4   St John's Medical College Hospital, Bangalore, India
,
Noppacharn Uaprasert
5   Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
6   Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
,
Jerzy Windyga
7   Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
,
Carmen Escuriola Ettingshausen
8   Haemophilia Centre Rhein Main, Frankfurt-Mörfelden, Germany
,
Bettina Ploder
9   Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
,
Aurelia Lelli
10   PDT R&D Global Medical Affairs, Takeda Pharmaceuticals International AG, Zurich, Switzerland
,
Hanna T. Gazda
11   Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States
› Author Affiliations Funding This study was funded by Baxalta US, Inc., and Baxalta Innovations GmbH (a Shire company), both now members of the Takeda group of companies.
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Abstract

Background Activated prothrombin complex concentrate (aPCC) is indicated for bleed treatment and prevention in patients with hemophilia with inhibitors. The safety and tolerability of intravenous aPCC at a reduced volume and faster infusion rates were evaluated.

Methods This multicenter, open-label trial (NCT02764489) enrolled adults with hemophilia A with inhibitors. In part 1, patients were randomized to receive three infusions of aPCC (85 ± 15 U/kg) at 2 U/kg/min (the approved standard rate at the time of the study), in a regular or 50% reduced volume, and were then crossed over to receive three infusions in the alternative volume. In part 2, patients received three sequential infusions of aPCC in a 50% reduced volume at 4 U/kg/min and then at 10 U/kg/min. Primary outcome measures included the incidence of adverse events (AEs), allergic-type hypersensitivity reactions (AHRs), infusion-site reactions (ISRs), and thromboembolic events.

Results Of the 45 patients enrolled, 33 received aPCC in part 1 and 30 in part 2. In part 1, 24.2 and 23.3% of patients with regular and reduced volumes experienced AEs, respectively; 11 AEs in eight patients were treatment related. AHRs and ISRs occurred in four (12.1%) and two (6.1%) patients, respectively. In part 2, 3.3 and 14.3% of patients with infusion rates of 4 and 10 U/kg/min experienced AEs, respectively; only one AE in one patient was treatment related; no AHRs or ISRs were reported. Most AEs were mild/moderate in severity. Overall, no thromboembolic events were reported.

Conclusions aPCC was well tolerated at a reduced volume and faster infusion rates, with safety profiles comparable to the approved regimen.

Keywords

aPCC - safety - treatment burden - hemophilia with inhibitors

Data Availability Statement

The data sets, including the redacted study protocol, redacted statistical analysis plan, and individual participant data supporting the results reported in this article, will be made available in the 3 months after the initial request to researchers who provide a methodologically sound proposal. The data will be provided after their de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.


Supplementary Material



Publication History

Received: 15 November 2023

Accepted: 17 May 2024

Article published online:
08 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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