Clinical Trial

. 2022 Jul;28(4):548-556.

doi: 10.1111/hae.14563. Epub 2022 Apr 27.

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Steven W Pipe¹, Cédric Hermans², Meera Chitlur³, Manuel Carcao⁴, Giancarlo Castaman⁵, Joanna A Davis⁶, Jonathan Ducore⁷, Amy L Dunn⁸, Miguel Escobar⁹, Janna Journeycake¹⁰, Osman Khan¹⁰, Johnny Mahlangu¹¹, Shannon L Meeks¹², Ismail Haroon Mitha¹³, Claude Négrier¹⁴, Ulrike Nowak-Göttl¹⁵, Michael Recht^{16

17}, Tammuella Chrisentery-Singleton¹⁸, Oleksandra Stasyshyn¹⁹, Kateryna V Vilchevska²⁰, Laura Villarreal Martinez²¹, Michael Wang²², Jerzy Windyga²³, Guy Young^{24

25}, W Allan Alexander²⁶, Daniel Bonzo²⁷, Christopher Macie²⁸, Ian S Mitchell²⁸, Evelyne Sauty²⁹, Thomas A Wilkinson³⁰, Amy D Shapiro³¹

Affiliations

¹ University of Michigan, Ann Arbor, Michigan, USA.
² Cliniques Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
³ Children's Hospital of Michigan, Central Michigan University, Detroit, Michigan, USA.
⁴ The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵ Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy.
⁶ Pediatric Hemophilia Treatment Center, University of Miami, Miami, Florida, USA.
⁷ Hematology/Oncology Clinic, University of California at Davis, Sacramento, California, USA.
⁸ Nationwide Children's Hospital, Department of Pediatrics at The Ohio State University College of Medicine, Columbus, Ohio, USA.
⁹ University of Texas Health Science Center at Houston, Houston, Texas, USA.
¹⁰ Oklahoma Center for Bleeding and Clotting Disorders at OU Health, Oklahoma City, Oklahoma, USA.
¹¹ Hemophilia Comprehensive Care Center, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.
¹² Emory University and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
¹³ Lakeview Hospital, Benoni, Gauteng, South Africa.
¹⁴ Edouard Herriot University Hospital, Lyon, France.
¹⁵ Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁶ American Thrombosis and Hemostasis Network, Rochester, New York, USA.
¹⁷ Oregon Health & Science University, Portland, Oregon, USA.
¹⁸ Louisiana Center for Advanced Medicine, Slidell, Louisiana, USA.
¹⁹ Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine.
²⁰ National Specialized Children's Hospital Okhmatdyt, Kyiv, Ukraine.
²¹ Dr. José Eleuterio González Monterrey University Hospital, Monterrey, Nuevo León, México.
²² Hemophilia and Thrombosis Center, University of Colorado, Aurora, Colorado, USA.
²³ Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
²⁴ Children's Hospital Los Angeles, Los Angeles, California, USA.
²⁵ Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
²⁶ Aoede Associates, Athens, Texas, USA.
²⁷ LFB-USA, Inc., Framingham, Massachusetts, USA.
²⁸ HEMA Biologics, LLC, Louisville, Kentucky, USA.
²⁹ LFB, Laboratoire français du fractionnement et des biotechnologies, Les Ulis, France.
³⁰ GLOVAL LLC, Broomfield, Colorado, USA.
³¹ Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA.

PMID: 35475308
PMCID: PMC9542908
DOI: 10.1111/hae.14563

Clinical Trial

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Steven W Pipe et al. Haemophilia. 2022 Jul.

. 2022 Jul;28(4):548-556.

doi: 10.1111/hae.14563. Epub 2022 Apr 27.

Authors

Affiliations

¹ University of Michigan, Ann Arbor, Michigan, USA.
² Cliniques Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
³ Children's Hospital of Michigan, Central Michigan University, Detroit, Michigan, USA.
⁴ The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵ Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy.
⁶ Pediatric Hemophilia Treatment Center, University of Miami, Miami, Florida, USA.
⁷ Hematology/Oncology Clinic, University of California at Davis, Sacramento, California, USA.
⁸ Nationwide Children's Hospital, Department of Pediatrics at The Ohio State University College of Medicine, Columbus, Ohio, USA.
⁹ University of Texas Health Science Center at Houston, Houston, Texas, USA.
¹⁰ Oklahoma Center for Bleeding and Clotting Disorders at OU Health, Oklahoma City, Oklahoma, USA.
¹¹ Hemophilia Comprehensive Care Center, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.
¹² Emory University and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
¹³ Lakeview Hospital, Benoni, Gauteng, South Africa.
¹⁴ Edouard Herriot University Hospital, Lyon, France.
¹⁵ Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁶ American Thrombosis and Hemostasis Network, Rochester, New York, USA.
¹⁷ Oregon Health & Science University, Portland, Oregon, USA.
¹⁸ Louisiana Center for Advanced Medicine, Slidell, Louisiana, USA.
¹⁹ Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine.
²⁰ National Specialized Children's Hospital Okhmatdyt, Kyiv, Ukraine.
²¹ Dr. José Eleuterio González Monterrey University Hospital, Monterrey, Nuevo León, México.
²² Hemophilia and Thrombosis Center, University of Colorado, Aurora, Colorado, USA.
²³ Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
²⁴ Children's Hospital Los Angeles, Los Angeles, California, USA.
²⁵ Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
²⁶ Aoede Associates, Athens, Texas, USA.
²⁷ LFB-USA, Inc., Framingham, Massachusetts, USA.
²⁸ HEMA Biologics, LLC, Louisville, Kentucky, USA.
²⁹ LFB, Laboratoire français du fractionnement et des biotechnologies, Les Ulis, France.
³⁰ GLOVAL LLC, Broomfield, Colorado, USA.
³¹ Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA.

PMID: 35475308
PMCID: PMC9542908
DOI: 10.1111/hae.14563

Abstract

Introduction: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older.

Aim: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors.

Methods: Using a randomised crossover design, subjects received initial doses of 75 or 225 μg/kg eptacog beta followed by 75 μg/kg dosing at predefined intervals (as determined by clinical response) to treat bleeding episodes (BEs). Treatment success criteria included a haemostasis evaluation of 'excellent' or 'good' without use of additional eptacog beta, alternative haemostatic agent or blood product, and no increase in pain following the first 'excellent' or 'good' assessment.

Results: Treatment success proportions in 25 subjects (1-11 years) who experienced 546 mild or moderate BEs were 65% in the 75 μg/kg initial dose regimen (IDR) and 60% in the 225 μg/kg IDR 12 h following initial eptacog beta infusion. By 24 h, the treatment success proportions were 97% for the 75 μg/kg IDR and 98% for the 225 μg/kg IDR. No thrombotic events, allergic reactions, neutralising antibodies or treatment-related adverse events were reported.

Conclusion: Both 75 and 225 μg/kg eptacog beta IDRs provided safe and effective treatment and control of bleeding in children <12 years of age.

Keywords: PERSEPT; eptacog beta; haemophilia; inhibitors; paediatric; recombinant FVIIa.

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Figures

**FIGURE 1**
(A) Subject dispositions for PERSEPT 2. (B) Treatment protocol for mild and moderate BEs in PERSEPT 2, with dosing schedules for 75 and 225 μg/kg IDRs indicated

**FIGURE 2**
Success proportions and 95% confidence intervals for mild or moderate BE treatment at 12 and 24 h

**FIGURE 3**
Anatomical distributions of the 546 mild or moderate BEs in PERSEPT 2. The percentage for each anatomical site of the total number of mild or moderate BEs is indicated

See this image and copyright information in PMC

References

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1. Neufeld EJ, Recht M, Sabio H, et al. Effect of acute bleeding on daily quality of life assessments in patients with congenital hemophilia with inhibitors and their families: observations from the dosing observational study in hemophilia. Value Health. 2012;15(6):916‐925. - PubMed
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Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Affiliations

Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical