Non-interventional Post-authorisation Study to Document the Immunogenicity, Safety, and Efficacy of NUWIQ

Study Overview
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Brief Summary
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Prospective, multinational, non-interventional post-authorisation study to collect additional clinical data and to ensure consistency in the long-term between the outcome from pre-authorisation clinical studies (in 135 previously treated paediatric and adult patients) and routine clinical practice. Besides aspects such as general product safety and efficacy, there will be a focus on immunogenicity, particularly on inhibitor development. The diagnosis of FVIII inhibitor will be based on clinical observations and confirmed by FVIII inhibitor testing in the laboratory.

Official Title
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Prospective, Multinational, Non-interventional Post-authorisation Study to Document the Long-term Immunogenicity, Safety, and Efficacy of Human-cl rhFVIII (Simoctocog Alfa) in Patients With Haemophilia A Treated in Routine Clinical Practice

Conditions
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Hemophilia A

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Haemophilia A (FVIII:C ≤ 2%) based on medical history; at least 100 patients should have severe haemophilia A (FVIII:C < 1%) Male patients of any age Previous treatment with a FVIII concentrate for more than 150 EDs Availability of detailed documentation (patient diary, log book, etc.) covering either the last 50 EDs or the last 2 years per patient to confirm treatment modality (i.e., prophylaxis, on-demand, recent surgery, or immune tolerance induction) Inhibitor negative (< 0.6 BU) at study entry as confirmed by a recovery test with previous FVIII product and inhibitor test in a central laboratory Immunocompetence (CD4+ count > 200/µL), HIV-negative, or having a viral load < 200 particles/µL or < 400,000 copies/mL Decision to prescribe Human-cl rhFVIII before enrolment into the study Written informed consent by the patient or the patient's parent or legal guardian Exclusion Criteria: Patients treated with any investigational medicinal product (IMP) except FVIII IMP within 30 days prior to the Screening Visit or patients planning to undergo treatment with any IMP other than Human-cl rhFVIII are not eligible for enrolment into the study.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With FVIII Inhibitors | FVIII inhibitors will be determined based on clinical observations and confirmed by FVIII inhibitor testing in the laboratory. | Screening through to study completion (minimum 1.7 months; maximum 31.6 months) | 
| Number of Patients With Adverse Drug Reactions | Adverse drug reactions (ADRs) including hypersensitivity reactions will be recorded by patients in treatment diaries which will be reviewed at each Follow-up Visit. | Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of Breakthrough Bleeds to Assess Efficacy in Prophylactic Treatment | Total number of bleeding episodes under prophylaxis treatment divided by the duration of prophylactic phase (in years) | Monitored throughout the study from screening through to study completion (minimum 3.7 months; maximum 21.2 months) | 
| Assessment of the Efficacy of On-demand Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale | At the end of a BE, treatment efficacy was to be assessed either by the patient (or the patient's parent or legal guardian) or by the treating physician in case of on-site treatment using a 4-point scale including the four items 'excellent,' 'good,' moderate,' and 'none.' Excellent result was defined as abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. Good was definite pain relief and/or improvement in signs of bleeding within approximately 8-12 hours after an injection requiring up to 2 injections for complete resolution. Moderate was probable or slight beneficial effect within approximately 12 hours after the first injection requiring more than two injections for complete resolution. None was no improvement after 12 hours, or worsening of symptoms, requiring more than 2 injections for complete resolution. | Monitored throughout the study from screening through to study completion (minimum 1.7 months; maximum 31.6 months) | 
| Overall Assessment of the Effectiveness of Surgical Prophylaxis by the Treating Physicians | At the end of the postoperative period, an overall assessment of the efficacy of treatment in the pre-, peri-, and postoperative periods using the 'excellent,' 'good,' moderate,' and 'none' scale will be done jointly by the surgeon and the hematologist. Based on this assessment, efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated'. | From start of surgery until end of post-operative period | 
| Assessment of the Efficacy of Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale | At the end of a BE, treatment efficacy was to be assessed either by the patient (or the patient's parent or legal guardian) or by the treating physician in case of on-site treatment using a 4-point scale including the four items 'excellent', 'good', 'moderate', and 'none.' Excellent result was defined as abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. Good was definite pain relief and/or improvement in signs of bleeding within approximately 8-12 hours after an injection requiring up to 2 injections for complete resolution. Moderate was probable or slight beneficial effect within approximately 12 hours after the first injection requiring more than two injections for complete resolution. None was no improvement after 12 hours, or worsening of symptoms, requiring more than 2 injections for complete resolution. | Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months) |