Nuwiq Dosing and Outcomes In the ManagEment of Women/Girls With Haemophilia A Needing FVIII Treatment for Surgery

Study Overview
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Brief Summary
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Recombinant factor VIII for the prevention of bleeding in women/girls with haemophilia A undergoing major surgery

Detailed Description
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Female patients with mild to moderate haemophilia A will often need FVIII concentrates to provide haemostatic cover during major surgery. This prospective, open-label, non-controlled, single-arm, multinational, multicentre study aims to evaluate the overall perioperative haemostatic efficacy of Nuwiq in women/girls over 12 with haemophilia A undergoing major surgery requiring FVIII treatment

Official Title
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Nuwiq Dosing and Outcomes In the ManagEment of Women/Girls With Haemophilia A Needing FVIII Treatment for Surgery - an International, Open-label, Non-controlled Study (NuDIMENSION)

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Nuwiq


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women/girls with haemophilia A (FVIII:C ≥1-<40%) according to medical history At least 12 years of age Scheduled to undergo 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) 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) Pregnancy 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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nuwiq<br>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<br>* Nuwiq is a purified B-domain-deleted FVIII glycoprotein synthesised by a genetically engineered human embryonic kidney cell line (HEK 293F).<br>|

What is the study measuring?
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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 up to 24 hours after last injection of Nuwiq | 

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 24 hours after the last injection of Nuwiq | 
| Allogenic blood products | Use of allogeneic blood products (red blood cells, platelets, and other blood products) | From day of surgery until 24 hours after the last injection of Nuwiq | 
| FVIII plasma levels | Perioperative plasma levels | Time Frame: <30 minutes before and <30 minutes after Nuwiq injection | 
| Perioperative haemostatic efficacy per WFH criteria | Assessed using 4-point scale recommended by WFH: Excellent: Intra- and post-operative blood loss similar to non-haemophilic patient. No extra doses of FVIII/bypassing agents needed Good: Intra- and/or post-operative blood loss slightly increased over expectation for non-haemophilic patient, but judged to be clinically insignificant. No extra doses of FVIII/bypassing agents needed Fair: Intra- and/or post-operative blood loss increased over expectation for the non-haemophilic patient, and additional treatment needed. Extra dose of FVIII/bypassing agents needed, or increased blood component of anticipated transfusion requirement Poor: Significant intra- and/or post-operative blood loss substantially increased over expectation for non-haemophilic patient, requires intervention not explained by medical issue other than haemophilia. Unexpected hypotension, unexpected transfer to ICU due to bleeding, substantially increased blood component of the anticipated transfusion requirement | Perioperative | 
| Adverse events | Incidence of adverse events recorded during the full study period | From start of first Nuwiq injection to 30 days following the surgical procedure | 
| Thrombotic events | Incidence of thrombotic events during the study | From start of first Nuwiq injection to 30 days following the surgical procedure | 
| FVIII inhibitor formation | Incidence of FVIII inhibitor formation | From start of first Nuwiq injection to 30 days following the surgical procedure |