Efficacy and Safety of Turoctocog Alfa Pegol (N8-GP) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A (pathfinder10)

Study Overview
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Brief Summary
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The study investigates how well the medicine called turoctocog alfa pegol (N8-GP) works in previously treated Chinese patients with severe haemophilia A. Participants will be treated with N8-GP. This is a medicine that doctors can already prescribe in other countries. The medicine will be injected into a vein (intravenous injections) and blood samples will be collected. The study will last for about 7-8 months. Participants will have between 8 and 15 visits to the clinic and possibly a number of phone calls with the study doctor.

Official Title
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A Multi-centre, Open-label Trial Evaluating Efficacy, Safety and Pharmacokinetics of Turoctocog Alfa Pegol (N8-GP) When Used for Treatment and Prophylaxis of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A

Conditions
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Haemophilia A

Intervention / Treatment
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* Drug: turoctocog alfa pegol (N8-GP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Male Chinese patient with severe congenital haemophilia A with a FVIII activity below 1% according to medical records. Aged greater than or equal to 12 years at the time of signing informed consent. History of at least 150 exposure days (EDs) to other FVIII products. The patient and/or caregiver is capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures at the discretion of the investigator. Exclusion Criteria: Known or suspected hypersensitivity to trial product or related products. Previous participation in this trial. Participation is defined as signed informed consent. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer. Known history of FVIII inhibitors based on existing medical records, laboratory report reviews and patient and/or caregiver interviews. Current FVIII inhibitors greater than or equal to 0.6 BU. Congenital or acquired coagulation disorder other than haemophilia According to medical records. HIV positive, defined by medical records, with CD4+ count less than or equal 200/L and a viral load greater than 200 particles/μl or greater than 400000 copies/mL within 6 months of the trial entry. If the data are not available in medical records within last 6 months, then the test must be performed at screening visit. Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening, as defined by central laboratory Renal impairment defined as estimated glomerular filtration rate (eGFR) below or equal to 30 mL/min/1.73 m^2 for serum creatinine measured at screening, as defined by central laboratory. Platelet count below 50×109/L at screening based on central laboratory values at screening. Ongoing immune modulating or chemotherapeutic medication. Any disorder, except for conditions associated with haemophilia A, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

Ages Eligible for Study
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Minimum Age: 12 Years

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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N8-GP prophylaxis<br>All patients will receive prophylaxis with 50 IU/kg N8-GP every 4 days for a treatment period of at least 28 weeks (with the possibility of switching to twice-weekly dosing during the treatment period at the discretion of the investigator). | Drug: turoctocog alfa pegol (N8-GP)<br>* N8-GP will be injected into a vein (intravenous injections) every 4 days in at least 28 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of bleeding episodes | Count | From start of treatment (week 0) until visit 7 (week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic effect of N8-GP when used for treatment of bleeding episodes, assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) | Count | From start of treatment (week 0) until visit 7 (week 28) | 
| Consumption of N8-GP for treatment of bleeding episodes | IU/kg/bleed | From start of treatment (week 0) until visit 7 (week 28) | 
| Consumption of N8-GP for prophylaxis | IU/kg/year | From start of treatment (week 0) until visit 7 (week 28) | 
| FVIII trough activity during prophylaxis | IU/mL | From start of treatment (week 0) (excluding the first exposure) until visit 7 (week 28) | 
| Incidence rate of confirmed FVIII inhibitors greater than or equal to 0.6 BU (Bethesda Units) | Rate | From start of treatment (week 0) until visit 7 (week 28) | 
| Number of adverse events (AEs) | Count | From start of treatment (week 0) to end of trial (week 28 + 30 days) | 
| Number of serious adverse events (SAEs) | Count | From start of treatment (week 0) to end of trial (week 28 + 30 days) | 
| FVIII activity 30 minutes post-injection (C30min) | IU/mL | Single-dose: 30 minutes plus/minus 5 minutes post-injection at visit 2a (week 0) | 
| FVIII activity 30 minutes post-injection (C30min) | IU/mL | Steady state: 30 minutes plus/minus 5 min post-injection at visit 7 (week 28) | 
| Incremental recovery (IR) | (IU/mL)/(IU/kg) | Single-dose: 30 minutes plus/minus 5 minutes post-injection at visit 2a (week 0) | 
| Incremental recovery (IR) | (IU/mL)/(IU/kg) | Steady state: 30 minutes plus/minus 5 minutes post-injection at visit 7 (week 28) | 
| Area under the curve (AUC) | hours*(IU/mL) | Single-dose: 0-inf post-injection at visit 2a (week 0) | 
| Area under the curve (AUC) | hours*(IU/mL) | Steady state: 0-inf post-injection at visit 7 (week 28) | 
| Terminal half-life (t½) | Hours | Single-dose: 0-96 hours post-injection at visit 2a (week 0) | 
| Terminal half-life (t½) | Hours | Steady state: 0-96 hours post-injection at visit 7 (week 28) | 
| Clearance (CL) | mL/h/kg | Single-dose: 0-96 hours post-injection at visit 2a (week 0) | 
| Clearance (CL) | mL/h/kg | Steady state: 0-96 hours post-injection at visit 7 (week 28) | 
| FVIII trough activity 96 hours post-injection (C96h) | IU/mL | Single-dose: 96 hours plus/minus 8 hours post-injection at visit 2a (week 0) | 
| FVIII trough activity 96 hours post-injection (C96h) | IU/mL | Steady state: 96 hours plus/minus 8 hours post-injection at visit 7 (week 28) |