Download PDF
CC BY-NC-ND 4.0 · TH Open 2023; 07(02): e110-e116
DOI: 10.1055/s-0043-1768464
Original Article

Design of a Real-World Observational Study in Previously Untreated and Minimally Treated Hemophilia A Patients: Protect-NOW

Johannes Oldenburg
1   Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
,
Susan Halimeh
2   Coagulation Centre Rhein-Ruhr, Duisburg, Germany
,
Georgina W. Hall
3   Oxford Haemophilia and Thrombosis Comprehensive Care Centre, Oxford University Hospital NHS Foundation Trust, Children's Hospital Oxford, Oxford, United Kingdom
,
Robert Klamroth
4   Department of Haemophilia and Haemostasis, Vivantes Hospital Friedrichshain, Berlin, Germany
,
Pascual Marco Vera
5   Department of Haematology, University General Hospital of Alicante, Alicante, Spain
,
Martina Jansen
6   Octapharma Pharmazeutika Produktionsges m.b.H., Vienna, Austria
,
Mary Mathias
7   Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom
› Author Affiliations Funding The Protect-NOW study is funded by Octapharma AG, Lachen, Switzerland. Medical writing assistance was provided by nspm ltd (Meggen, Switzerland) and funded by Octapharma AG.
› Further Information
   Permissions and Reprints

Abstract

Background The efficacy, safety, and immunogenicity of each of Octapharma's factor VIII (FVIII) products, Nuwiq, octanate, and wilate, have been investigated in previously untreated patients (PUPs) with severe hemophilia A in prospective clinical trials. The aim of the Protect-NOW study is to evaluate the effectiveness, safety, and utilization patterns of Nuwiq, octanate, and wilate in PUPs and minimally treated patients (MTPs; <5 exposure days [EDs] to FVIII concentrates or other blood products containing FVIII) with severe hemophilia A in a real-world setting. Real-world data provide valuable information that complement data obtained from interventional clinical trials.

Methods Protect-NOW (ClinicalTrials.gov identifier: NCT03695978; ISRCTN identifier: 11492145) is a real-world study in PUPs and MTPs treated with either the human cell line-derived recombinant FVIII Nuwiq (simoctocog alfa) or a plasma-derived FVIII concentrate containing von Willebrand factor (octanate or wilate). It is a prospective and (partly) retrospective, observational, international, noncontrolled, noninterventional study. A total of 140 PUPs and MTPs with severe hemophilia A will be enrolled across around 50 specialized centers worldwide and followed for either 100 EDs or a maximum period of 3 years from ED1. The primary objectives are to assess effectiveness in the prevention and treatment of bleeding episodes and overall safety, including inhibitor development. The secondary objectives are to assess utilization patterns (including dosage and frequency of administration) and the effectiveness in surgical prophylaxis.

Conclusions The Protect-NOW study will provide information on the treatment of PUPs and MTPs in routine clinical practice, which will help guide clinical decision making for treating these patients in the future.

Keywords

coagulation factor VIII - hemophilia A - inhibitors - previously untreated patients - real-world study


Publication History

Received: 03 January 2023

Accepted: 24 March 2023

Article published online:
10 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Coppola A, Di Capua M, Di Minno MN. et al. Treatment of hemophilia: a review of current advances and ongoing issues. J Blood Med 2010; 1: 183-195
    CrossrefPubMedGoogle Scholar
  • 2 Franchini M. The modern treatment of haemophilia: a narrative review. Blood Transfus 2013; 11 (02) 178-182
    PubMedGoogle Scholar
  • 3 Srivastava A, Santagostino E, Dougall A. et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia 2020; 26: 1-158
    CrossrefPubMedGoogle Scholar
  • 4 Kulkarni R, Soucie JM. Pediatric hemophilia: a review. Semin Thromb Hemost 2011; 37 (07) 737-744
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Ljung RCR. Prevention and management of bleeding episodes in children with hemophilia. Paediatr Drugs 2018; 20 (05) 455-464
    CrossrefPubMedGoogle Scholar
  • 6 Andersson NG, Auerswald G, Barnes C. et al. Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment. Br J Haematol 2017; 179 (02) 298-307
    CrossrefPubMedGoogle Scholar
  • 7 Manco-Johnson MJ, Abshire TC, Shapiro AD. et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357 (06) 535-544
    CrossrefPubMedGoogle Scholar
  • 8 Warren BB, Thornhill D, Stein J. et al. Young adult outcomes of childhood prophylaxis for severe hemophilia A: results of the Joint Outcome Continuation Study. Blood Adv 2020; 4 (11) 2451-2459
    CrossrefPubMedGoogle Scholar
  • 9 Carcao M, Escuriola-Ettingshausen C, Santagostino E. et al; Future of Immunotolerance Treatment Group. The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia 2019; 25 (04) 676-684
    CrossrefPubMedGoogle Scholar
  • 10 van den Berg HM, Fischer K, Carcao M. et al; PedNet Study Group. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood 2019; 134 (03) 317-320
    CrossrefPubMedGoogle Scholar
  • 11 Goudemand J, Peyvandi F, Lacroix-Desmazes S. Key insights to understand the immunogenicity of FVIII products. Thromb Haemost 2016; 116 (Suppl. 01) S2-S9
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Klukowska A, Szczepański T, Vdovin V, Knaub S, Jansen M, Liesner R. Novel, human cell line-derived recombinant factor VIII (Human-cl rhFVIII, Nuwiq®) in children with severe haemophilia A: efficacy, safety and pharmacokinetics. Haemophilia 2016; 22 (02) 232-239
    CrossrefPubMedGoogle Scholar
  • 13 Klukowska A, Szczepański T, Vdovin V. et al. Long-term tolerability, immunogenicity and efficacy of Nuwiq® (human-cl rhFVIII) in children with severe haemophilia A. Haemophilia 2018; 24 (04) 595-603
    CrossrefPubMedGoogle Scholar
  • 14 Liesner RJ, Abraham A, Altisent C. et al. Simoctocog alfa (Nuwiq) in previously untreated patients with severe haemophilia A: final results of the NuProtect study. Thromb Haemost 2021; 121 (11) 1400-1408
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Klukowska A, Komrska V, Vdovin V. et al. octanate®: over 20 years of clinical experience in overcoming challenges in haemophilia A treatment. Ther Adv Hematol 2020; 11: 2040620720914692
    CrossrefPubMedGoogle Scholar
  • 16 Kulkarni R, Presley RJ, Lusher JM. et al. Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System. Haemophilia 2017; 23 (02) 207-214
    CrossrefPubMedGoogle Scholar
  • 17 Nijdam A, Altisent C, Carcao MD. et al; PedNet and CANAL study groups. Bleeding before prophylaxis in severe hemophilia: paradigm shift over two decades. Haematologica 2015; 100 (03) e84-e86
    CrossrefPubMedGoogle Scholar
  • 18 Witmer C, Presley R, Kulkarni R, Soucie JM, Manno CS, Raffini L. Associations between intracranial haemorrhage and prescribed prophylaxis in a large cohort of haemophilia patients in the United States. Br J Haematol 2011; 152 (02) 211-216
    CrossrefPubMedGoogle Scholar
  • 19 Neufeld EJ, Liesner RJ. Efficacy of simoctocog alfa in previously untreated patients with severe haemophilia A: final Results from the NuProtect study. Res Pract Thromb Haemost 2021; 5 (Suppl. 02) 447
    PubMedGoogle Scholar
  • 20 Klukowska A, Komrska V, Vdovin V. et al. Low incidence of factor VIII inhibitors in previously untreated patients with severe haemophilia A treated with octanate® : final report from a prospective study. Haemophilia 2018; 24 (02) 221-228
    CrossrefPubMedGoogle Scholar
  • 21 Carcao M, Mancuso ME, Young G, Jiménez-Yuste V. Key questions in the new hemophilia era: update on concomitant use of FVIII and emicizumab in hemophilia A patients with inhibitors. Expert Rev Hematol 2021; 14 (02) 143-148
    CrossrefPubMedGoogle Scholar
  • 22 Pipe SW. Delivering on the promise of gene therapy for haemophilia. Haemophilia 2021; 27 (Suppl. 03) 114-121
    CrossrefPubMedGoogle Scholar
  • 23 Garagiola I, Palla R, Peyvandi F. Risk factors for inhibitor development in severe hemophilia A. Thromb Res 2018; 168: 20-27
    CrossrefPubMedGoogle Scholar
  • 24 Peyvandi F, Mannucci PM, Garagiola I. et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med 2016; 374 (21) 2054-2064
    CrossrefPubMedGoogle Scholar
  • 25 Rosendaal FR, Palla R, Garagiola I, Mannucci PM, Peyvandi F. SIPPET Study Group. Genetic risk stratification to reduce inhibitor development in the early treatment of hemophilia A: a SIPPET analysis. Blood 2017; 130 (15) 1757-1759
    CrossrefPubMedGoogle Scholar
  • 26 Liesner R, Versteden J, Lowndes S, Belyanskaya L, Oldenburg J, Pavlova A. Immunogenicity of two plasma-derived FVIII products and simoctocog alfa in previously untreated patients according to F8 mutation type. Blood 2018; 132: 1204
    CrossrefPubMedGoogle Scholar
  • 27 Le Quellec S. Clinical evidence and safety profile of emicizumab for the management of children with hemophilia A. Drug Des Devel Ther 2020; 14: 469-481
    CrossrefPubMedGoogle Scholar
  • 28 Aledort L, Mannucci PM, Schramm W, Tarantino M. Factor VIII replacement is still the standard of care in haemophilia A. Blood Transfus 2019; 17 (06) 479-486
    PubMedGoogle Scholar