A Post-Authorization Safety Surveillance Study to Report Clinical Experience with Purified Factor IX Concentrate in Pediatric Patients with Hemophilia B

Abstract

Introduction

Purified factor IX (FIX) concentrate (IMMUNINE^®, Takeda Manufacturing Austria AG, Vienna, Austria) is indicated for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia B. Data on the use of purified FIX concentrate in patients ≤6 years old with congenital hemophilia B are limited.

Aim

Document real-world clinical experience with purified FIX concentrate in routine practice for pediatric patients with hemophilia B.

Methods

This prospective post-authorization safety surveillance study enrolled patients ≤6 years old with moderate or severe hemophilia B (baseline FIX ≤5%) who were prescribed purified FIX concentrate, as determined by the treating physician. The planned observation period for each patient was either 12 months or ≥50 exposure days, whichever occurred first. The primary endpoints were the occurrence of treatment-related adverse events (AEs) and serious AEs (SAEs), and inhibitor development.

Results

Thirteen male patients (mean ± standard deviation age, 3.80 ± 1.76 years) enrolled and received ≥1 treatment with purified FIX concentrate. Thirty-two AEs were reported in 6 patients; 4 were SAEs. No AEs were considered related to purified FIX concentrate. No patients developed inhibitory antibodies. Inhibitor testing was not conducted in 2 patients. Eighteen bleeding episodes were treated with purified FIX concentrate in 6 patients. Hemostatic efficacy was rated as either “excellent” or “good” in all patients with an available rating.

Conclusion

No treatment-related AEs were reported, and purified FIX concentrate was shown to be effective in treating and preventing bleeding episodes in pediatric patients ≤6 years old with hemophilia B.

Keywords:

• factor IX
• hemophilia B
• pediatrics
• post-marketing product surveillance
• surgery

Abbreviations

AE, adverse event; BU, Bethesda units; ED, exposure day; FIX, factor IX; ITT, intent to treat; PASS, post-authorization safety surveillance; PP, per protocol; SAE, serious adverse event; SD, standard deviation; WFH, World Federation of Hemophilia.

Data Sharing Statement

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

Ethics Approval and Informed Consent

The study was conducted in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice E6, Title 21 of the US Code of Federal Regulations, the European Clinical Trial Directive, and applicable national and local regulatory requirements, including European regulations pertaining to PASS studies. This study was also conducted in accordance with the Declaration of Helsinki. Approval from Institutional Review Boards/Independent Ethics Committees, listed in Supporting Information, was obtained for the study protocol and informed consent form. All patients or their legally authorized representative signed an informed consent form prior to entering the study.

Acknowledgments

Under the direction of the authors, medical writing support was provided by Sarah Morgan, PhD, employee of Excel Scientific Solutions, Inc., a member of the Envision Pharma Group (Fairfield, Connecticut, USA), and was funded by Takeda Development Center Americas, Inc., Lexington, Massachusetts, USA.

Material from this manuscript was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress; July 09–13, 2022. Abstract title: A post-authorization safety surveillance study to report clinical experience with purified factor IX concentrate in pediatric patients with hemophilia B. https://abstracts.isth.org/abstract/a-post-authorization-safety-surveillance-study-to-report-clinical-experience-with-purified-fix-concentrate-in-pediatric-patients-with-hemophilia-b/.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Zoran Igrutinović reports being an investigator for this post-authorization safety surveillance study, which was funded by Baxalta Innovations GmbH, Vienna, Austria, a Takeda company. Hélène Louise Hooimeijer has no interests that might be perceived as posing a conflict or bias for this study. Karim Kentouche reports being an investigator for this post-authorization safety surveillance study, which was funded by Baxalta Innovations GmbH, Vienna, Austria, a Takeda company. Jaco Botha and Marta Kokot-Kierepa are employees of Takeda Pharmaceuticals International AG, and Takeda stockholders. Peter L. Turecek is an employee of Baxalta Innovations GmbH, a Takeda company, and a Takeda stockholder. Hanna T. Gazda is an employee of Takeda Development Center Americas, Inc., a Takeda company, and a Takeda shareholder. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Baxalta Innovations GmbH, Vienna, Austria, a Takeda company.