Hemophilia A
Conditions
Brief summary
Recombinant factor VIII for the prevention of bleeding in women/girls with haemophilia A undergoing major surgery
Detailed description
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
Interventions
DRUGNuwiq
Nuwiq is a purified B-domain-deleted FVIII glycoprotein synthesised by a genetically engineered human embryonic kidney cell line (HEK 293F).
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women/girls with haemophilia A (FVIII:C ≥1-\<40%) according to medical history. Additionally, women/girls with documented FVIII activity levels between ≥ 40% and 50% may be included if there is a documented history of clinically significant bleeding episodes consistent with haemophilia A; and/or either documented prior treatment with FVIII concentrates or a clinical indication that FVIII treatment would have been appropriate (e.g., use of FVIII from a family member, or treatment with alternative haemostatic agents due to access limitations) 2. At least 12 years of age 3. Scheduled to undergo major surgery\* requiring FVIII treatment, including elective and emergency procedures and caesarean section in pregnant women with haemophilia A 4. Freely given written informed consent of the patient, or parent/legal representative where applicable, obtained in accordance with local regulations
Exclusion criteria
1. Coagulation disorder other than haemophilia A 2. Present or past FVIII inhibitor (≥0.6 Bethesda units \[BU\]/mL) 3. 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) 4. Known hypersensitivity to Nuwiq's active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188) 5. Pregnancy, except in participants with a planned caesarean section 6. Already had surgery in this study 7. Current participation in another interventional clinical trial 8. Treatment with any investigational medicinal product (IMP) within 30 days prior to screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall haemostatic efficacy | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative haemostatic efficacy | During surgery: From first skin incision to last suture | 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. |
| Postoperative haemostatic efficacy | 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 | 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. |
| Allogenic blood products | 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 | Use of allogeneic blood products (red blood cells, platelets, and other blood products) |
| FVIII plasma levels | ≤30 minutes before and 15-30 minutes after Nuwiq injection | Perioperative plasma levels |
| Perioperative haemostatic efficacy per WFH criteria | ≤30 minutes before and 15-30 minutes after Nuwiq injection | 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 |
| Adverse events | From start of first Nuwiq injection to 30 ±3 days following the surgical procedure | Incidence of adverse events recorded during the full study period |
| Thrombotic events | From start of first Nuwiq injection to 30 ±3 days following the surgical procedure | Incidence of thrombotic events during the study |
| FVIII inhibitor formation | From start of first Nuwiq injection to 30 ±3 days following the surgical procedure | Incidence of FVIII inhibitor formation |
Countries
Finland, France, Germany, Italy, Serbia, Spain, Switzerland, United Kingdom, United States, Uruguay
Contacts
CONTACTCristina Solomon
PRINCIPAL_INVESTIGATORJohannes Oldenburg
Experimental Haematology and Transfusion Medicine, University Clinic Bonn
Outcome results
None listed