A Research Study Investigating Nonacog Beta Pegol (N9-GP) for Treatment and Prevention of Bleedings in Chinese People With Haemophilia B

Study Overview
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Brief Summary
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The study investigates how well the medicine called nonacog beta pegol (N9-GP) works in Chinese people with haemophilia B. Participants will be treated with N9-GP. This is a medicine that doctors can already prescribe in other countries. The medicine will be injected into a vein (intravenous injection). At the visits to the clinic, the medicine will be injected by the study doctor. When treating themselves at home, participants inject the medicine using a needle and vial set. The study will last for about 12-16 months. The participants will have between 9 and 19 visits to the clinic and possibly also some phone calls with the study doctor. At all visits to the clinic, the participants will have blood samples taken.

Official Title
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A Multi-centre, Open-label Trial Evaluating Efficacy, Safety and Pharmacokinetics of Nonacog Beta Pegol When Used for Treatment and Prophylaxis of Bleeding Episodes in Chinese Patients With Haemophilia B

Conditions
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Haemophilia B

Intervention / Treatment
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* Drug: Nonacog beta pegol


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 moderate to severe congenital haemophilia B with a factor IX (FIX) activity less than or equal to 2 percent according to medical records. Aged 12-70 years (both inclusive) at the time of signing informed consent. History of at least 100 exposure days (EDs) to products containing FIX.1. Patients currently on prophylaxis or patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months. The patient, legally authorised representative (LAR) and/or caregiver are capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures. 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 FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR interviews. Current FIX inhibitors greater than or equal to 0.6 Bethesda unit (BU). HIV positive, defined by medical records, with CD4+ count less than or equal 200 per microlitre (μL) and a viral load greater than 200 particles per microlitre or greater than 400000 copies per millilitre (mL) within 6 months of the trial entry. If the data are not available in the medical records within the last 6 months, then the test must be performed at the screening visit. Congenital or acquired coagulation disorder other than haemophilia B. Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records). Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening. Renal impairment defined as estimated glomerular filtration rate (eGFR) less than or equal to 30 mL/min/1.73 m^2 for serum creatinine measured at screening. Any disorder, except for conditions associated with haemophilia B, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol. Platelet count less than 50×10^9/L at screening. Immune modulating or chemotherapeutic medication. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A - Nonacog beta pegol (On-demand/Prophylaxis)<br>Participants on on-demand treatment for 28 weeks, thereafter prophylactic treatment | Drug: Nonacog beta pegol<br>* Nonacog beta pegol is administered as intravenous injections. Participants will receive nonacog beta pegol as prophylaxis, as on-demand for treatment of bleeding episodes and in relation to surgery.<br>|
| Experimental: Arm B - Nonacog beta pegol (Prophylaxis)<br>Participants on prophylactic treatment only | Drug: Nonacog beta pegol<br>* Nonacog beta pegol is administered as intravenous injections. Participants will receive nonacog beta pegol as prophylaxis, as on-demand for treatment of bleeding episodes and in relation to surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic effect of nonacog beta pegol when used for treatment of bleeding episodes during on-demand and PPX | Measured as count. Assessed as success/failure based on a four-point scale for haemostatic response (excellent, good, moderate and none) by counting excellent and good as 'success' and moderate and none as 'failure' | From start of treatment (week 0) until end of treatment (week 50) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treated bleeding episodes during PPX treatment (Arm B only) | Number of episodes | From start of treatment (week 0) until end of treatment (week 50) | 
| Consumption of nonacog beta pegol for treatment of bleeding episodes | Measured in International units per kilogram (IU/kg) per bleed | From start of treatment (week 0) until end of treatment (week 50) | 
| Consumption of nonacog beta pegol for PPX treatment (Arm B only) | Measured in IU/kg per year | From start of treatment (week 0) until end of treatment (week 50) | 
| FIX trough levels during PPX treatment (Arm B only) | Measured in International units per millilitre (IU/mL) | From start of treatment (week 0) until end of treatment (week 50) | 
| Number of patients with inhibitory antibodies against FIX defined as titre above or equal to 0.6 Bethesda units (BU) | Number of participants | From start of treatment (week 0) until end of treatment (week 50) | 
| Number of adverse events (AEs) | Number of events | From start of treatment (week 0) until end of treatment (week 50) | 
| Number of serious adverse events (SAEs) | Number of events | From start of treatment (week 0) until end of treatment (week 50) | 
| Incremental recovery (IR) (Arm B only) | Measured in (IU/mL)/(IU/kg) | Single-dose: 30±10 minutes post-injection at week 0; Steady-state: 30±10 minutes post-injection at week 12 | 
| Terminal half-life (t½) (Arm B only) | Measured in hours (h) | Single-dose: 0-168 hours post-injection at week 0; Steady-state: 0-168 hours post-injection at week 12 | 
| Clearance (CL) (Arm B only) | Measured in mL/h/kg | Single-dose: 0-168 hours post injection at week 0; Steady-state: 0-168 hours post injection at week 12 | 
| Area under the curve (AUC) (Arm B only) | Measured in h·IU/mL | Single-dose: 0-168 hours post injection at week 0; Steady-state: 0-168 hours post injection at week 12 |