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

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

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

Study Overview

• Status: Recruiting
• Conditions: Severe Hemophilia A
• Intervention / Treatment: Drug: Nuwiq

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sigurd Knaub, PhD; Phone Number: +41 554512141; Email: Sigurd.Knaub@octapharma.com

Study Locations

• Croatia
  • Zagreb, Croatia
    • Recruiting
    • University Hospital Centre Zagreb
• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
• France
  • Nantes, France
    • Recruiting
    • CHU de Nantes Hôtel-Dieu
  • Tours, France
    • Recruiting
    • CHRU de Tours
• Germany
  • Berlin, Germany
    • Recruiting
    • Vivantes Klinikum im Friedrichshein (KFH)
  • Duisburg, Germany
    • Recruiting
    • Gerinnungszentrum Rhein-Ruhr
  • Hamburg, Germany
    • Recruiting
    • Universitätsklinikum Hamburg Eppendorf (UKE)
• India
  • Bengaluru, India
    • Recruiting
    • St. John's Medical College Hospital
  • Tamil Nadu
    • Vellore, Tamil Nadu, India
      • Recruiting
      • Christian Medical College Vellore
• Italy
  • Catanzaro, Italy
    • Recruiting
    • Azienda Ospedaliera Pugliese Ciaccio
  • Florence, Italy
    • Recruiting
    • Azienda Ospedaliero Universitaria Careggi - Centro Emofilia
  • Milan, Italy
    • Recruiting
    • Centro Trombosi e Malattie Emorragiche, ITCCS Humanitas Research Hospital
• North Macedonia
  • Skopje, North Macedonia
    • Recruiting
    • Centre for Haemopilia, Institute for transfusion medicine of Republic of North Macedonia
• Serbia
  • Belgrade, Serbia
    • Recruiting
    • Clinical Center for Serbia Belgrade
• Spain
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Seville, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
• United Kingdom
  • Leeds, United Kingdom
    • Not yet recruiting
    • St. James's University Hospital
• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nuwiq; All patients receiving Nuwiq (recombinant FVIII). Nuwiq will be administered intravenously in accordance with the relevant prescribing information. Treatment will be repeated as necessary every 8-24 hours until adequate wound healing, then - if required - for at least another 7 days to maintain FVIII plasma levels of 30-60 IU/dL.	Drug: Nuwiq; Nuwiq is a purified B-domain-deleted FVIII glycoprotein synthesised by a genetically engineered human embryonic kidney cell line (HEK 293F).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall haemostatic efficacy	Overall haemostatic efficacy of treatment measured as binary "success" or "failure". The overall perioperative haemostatic efficacy of Nuwiq will be adjudicated by an Independent Data Monitoring Committee (IDMC) and determined using a composite assessment algorithm that considers the surgeon's assessment of intraoperative haemostatic efficacy and the investigator's assessment of postoperative haemostatic efficacy to classify the overall haemostatic efficacy as success or failure.	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

Outcome Measure	Measure Description	Time Frame
Intraoperative haemostatic efficacy	Assessment of intraoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale: Excellent: Intraoperative blood loss was lower than or equal to the average expected blood loss for the type of procedure performed in a patient with normal haemostasis and of the same sex, age, and stature Good: Intraoperative blood loss was higher than the average expected blood loss but lower or equal to the maximal expected blood loss for the type of procedure in a patient with normal haemostasis. Moderate: Intraoperative blood loss was higher than the maximum expected blood loss for the type of procedure performed in a patient with normal haemostasis, but haemostasis was controlled. None: Haemostasis was uncontrolled, necessitating a change in the clotting factor replacement regimen.	During surgery: From first skin incision to last suture
Postoperative haemostatic efficacy	Assessment of postoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale: Excellent: No postoperative bleeding or oozing that was not due to complications of surgery. All postoperative bleeding (due to complications of surgery) was controlled with Nuwiq as anticipated for the type of procedure. Good: No postoperative bleeding or oozing that was not due to complications of surgery. Control of postoperative bleeding due to complications of surgery required increased dosing with Nuwiq or additional injections not originally anticipated for the type of procedure. Moderate: Some postoperative bleeding and oozing that was not due to complications of surgery. Control of postoperative bleeding required increased dosing with Nuwiq or additional injections not originally anticipated for the type of procedure. None: Extensive uncontrolled postoperative bleeding and oozing.	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	The number of allogeneic blood products (red blood cells, platelets, and other blood products) transfused	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	Perioperative plasma levels	≤30 minutes before and 15-30 minutes after Nuwiq injection
Thrombin generation	Perioperative thrombin generation	≤30 minutes before and 15-30 minutes after Nuwiq injection
Perioperative haemostatic efficacy per World Federation of Hemophilia (WFH) criteria	Assessed on WFH recommended 4-point scale: Excellent: Intra and post-operative blood loss, with blood component transfusions, similar to non-haemophilic patients. No additional FVIII/bypassing agents Good: Intra/ post-operative blood loss slightly increased over expectation for non-haemophilic patient but clinically insignificant. Blood component transfusions similar to non-haemophilic patient. No additional FVIII/bypassing agents Fair: Intra/ post-operative blood loss increased over expectation for non-haemophilic patients, and additional treatment needed. Extra dose of FVIII/bypassing agents needed or increased blood component of anticipated transfusion requirement Poor: Significant intra- or post-operative blood loss substantially increased over non-haemophilic patient, requires haemophilia-related medical intervention. Unexpected hypotension, transfer to ICU due to bleeding or substantially increased blood component of anticipated transfusion requirement	Perioperative
Thrombotic events	Incidence of thrombotic events during the study	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	Incidence of FVIII inhibitor formation	From start of first Nuwiq injection to 30 ± 3 days following the surgical procedure or until day of discharge, whichever is later
Adverse events	Incidence of adverse events recorded during the full study period	From start of first Nuwiq injection to 30 ± 3 days following the surgical procedure or until day of discharge, whichever is later

Collaborators and Investigators

• Sponsor: Octapharma
• Investigators: Principal Investigator: Shveta Gupta, MD, Arnold Palmer Hospital for Children

Publications and helpful links

General 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, single-arm, multicentre study. BMJ Open. 2025 Oct 28;15(10):e102657. doi: 10.1136/bmjopen-2025-102657.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Blood Proteins; Blood Coagulation Factors; Protein Precursors; Factor VIII
• Other Study ID Numbers: GENA-22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No