Nuwiq for Perioperative Management Of Patients With Haemophilia A on Emicizumab Regular Prophylaxis Study

Official title

Nuwiq for Perioperative Management Of Patients With Haemophilia A on Emicizumab Regular Prophylaxis Study (NuPOWER)

Overview

Recombinant factor VIII for the prevention of bleeding in patients with severe haemophilia A undergoing major surgery while receiving emicizumab prophylaxis

Detailed description

Patients with severe haemophilia A receiving emicizumab will often need concomitant FVIII to provide haemostatic cover during major surgery. This prospective, open-label, uncontrolled, single-arm, multinational, multicentre study aims to evaluate the overall perioperative haemostatic efficacy of Nuwiq, a recombinant factor VIII, in combination with emicizumab prophylaxis in male patients over 12 with severe haemophilia A undergoing major surgery.

Interventions

• Drug Nuwiq
  Nuwiq is a purified B-domain-deleted FVIII glycoprotein synthesised by a genetically engineered human embryonic kidney cell line (HEK 293F).

Primary outcome measures

• Overall haemostatic efficacy [Time frame: During surgery and until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure]

Secondary outcome measures (9)

• Intraoperative haemostatic efficacy [Time frame: During surgery: From first skin incision to last suture]
• Postoperative haemostatic efficacy [Time frame: From end of surgery until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure]
• Blood product transfusion levels [Time frame: From day of surgery until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure]
• FVIII plasma levels [Time frame: ≤30 minutes before and 15-30 minutes after Nuwiq injection]
• Thrombin generation [Time frame: ≤30 minutes before and 15-30 minutes after Nuwiq injection]
• Perioperative haemostatic efficacy per World Federation of Hemophilia (WFH) criteria [Time frame: Perioperative]
• Thrombotic events [Time frame: From start of first Nuwiq injection to 30 ± 3 days following the surgical procedure or until day of discharge, whichever is later]
• FVIII inhibitor formation [Time frame: From start of first Nuwiq injection to 30 ± 3 days following the surgical procedure or until day of discharge, whichever is later]
• Adverse events [Time frame: From start of first Nuwiq injection to 30 ± 3 days following the surgical procedure or until day of discharge, whichever is later]

Eligibility criteria

Inclusion criteria

• Severe haemophilia A (FVIII activity \[FVIII:C\] <1%) according to medical history
• Male patients at least 12 years of age
• Previous treatment with any FVIII product(s) for at least 150 exposure days
• On regular prophylaxis with emicizumab for at least 1 month prior to a scheduled major elective surgery requiring FVIII treatment
• Freely given written informed consent of the patient, or parent/legal representative where applicable, obtained in accordance with local regulations

Exclusion criteria

• Coagulation disorder other than haemophilia A
• Present or past FVIII inhibitor (≥0.6 Bethesda units \[BU\]/mL) according to medical history
• Severe liver or kidney disease (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\] levels >5 times the upper limit of normal; or creatinine >120 μmol/L)
• Known hypersensitivity to Nuwiq's active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188)
• Already had surgery in this study
• Current participation in another interventional clinical trial
• Treatment with any investigational medicinal product (IMP) within 30 days prior to screening visit

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 3 centers

• Vivantes Klinikum im Friedrichshein (KFH) — Berlin
• Gerinnungszentrum Rhein-Ruhr — Duisburg
• Universitätsklinikum Hamburg Eppendorf (UKE) — Hamburg

Italy · 3 centers

• Azienda Ospedaliera Pugliese Ciaccio — Catanzaro
• Azienda Ospedaliero Universitaria Careggi - Centro Emofilia — Florence
• Centro Trombosi e Malattie Emorragiche, ITCCS Humanitas Research Hospital — Milan

France · 2 centers

• CHU de Nantes Hôtel-Dieu — Nantes
• CHRU de Tours — Tours

India · 2 centers

• Christian Medical College Vellore — Vellore
• St. John's Medical College Hospital — Bengaluru

Spain · 2 centers

• Hospital Universitario La Paz — Madrid
• Hospital Universitario Virgen del Rocio — Seville

United States · 1 center

• UT Southwestern Medical Center — Dallas

Croatia · 1 center

• University Hospital Centre Zagreb — Zagreb

Finland · 1 center

• Helsinki University Hospital — Helsinki

North Macedonia · 1 center

• Centre for Haemopilia, Institute for transfusion medicine of Republic of North Macedonia — Skopje

Serbia · 1 center

• Clinical Center for Serbia Belgrade — Belgrade

United Kingdom · 1 center

• St. James's University Hospital — Leeds

Publications

• Srivastava A, Kanny A, Langer F, Kubicek-Hofmann C, Alvarez Roman MT, Nunez Vazquez R, Boban A, Dejanova-Ilijevska V, Miljic P, Garcia J, Halimeh S, Drillaud N, Valentin JB, Mancuso ME, Castaman G, Santoro RC, Lehtinen AE, Abraham A, Hashimoto M, Knaub S. NuPOWER (Nuwiq for Perioperative management Of patients With haemophilia A on Emicizumab Regular prophylaxis): protocol for an open-label, singl PMID 41151952

Identifiers

NCT: NCT05935358 · GENA-22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗