Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients

Study Overview
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Brief Summary
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This trial is conducted in Africa, Asia, Europe, Japan and North America. The aim of this trial is to evaluate the safety and efficacy, including pharmacokinetics (the rate at which the body eliminates the trial drug), of NNC-0156-0000-0009 (nonacog beta pegol) when used for treatment and prophylaxis of bleeding episodes in patients with haemophilia B.

Official Title
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A Multi-centre, Single-blind Trial Evaluating Safety and Efficacy, Including Pharmacokinetics, of NNC-0156-0000-0009 When Used for Treatment and Prophylaxis of Bleeding Episodes in Patients With Haemophilia B

Conditions
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Congenital Bleeding Disorder, Haemophilia B

Intervention / Treatment
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* Drug: nonacog beta pegol
* Drug: nonacog beta pegol
* Drug: nonacog beta pegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients with moderately severe or severe congenital haemophilia B with a factor IX activity of 2% or below according to medical records History of at least 150 exposure days to other factor IX products 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, or patients currently on prophylaxis Exclusion Criteria: Known history of factor IX inhibitors based on existing medical records, laboratory report reviews and patient and legally acceptable representative (LAR) interviews HIV (Human immunodeficiency virus) positive, with a viral load equal to or above 400,000 copies/mL and/or CD4+ lymphocyte count equal to or below 200/microL Congenital or acquired coagulation disorders 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) Immune modulating or chemotherapeutic medication

Ages Eligible for Study
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Minimum Age: 13 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylaxis, high dose (trial duration 52 weeks)<br> | Drug: nonacog beta pegol<br>* One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience<br>* Other names: NNC-0156-0000-0009;|
| Experimental: Prophylaxis, low dose (trial duration 52 weeks)<br> | Drug: nonacog beta pegol<br>* One single dose administered intravenously (into the vein) once weekly. Patients will receive instruction on how to treat any bleeding episode they may experience<br>* Other names: NNC-0156-0000-0009;|
| Experimental: On-demand (trial duration 28 weeks)<br> | Drug: nonacog beta pegol<br>* Patients will treat themselves with either a low or a high dose dependent on the severity of the bleeding episode<br>* Other names: NNC-0156-0000-0009;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units) | Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of subjects who developed inhibitory antibodies against factor IX are reported. | 52 weeks after treatment start for patients on prophylaxis | 
| Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units) | Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of subjects who developed inhibitory antibodies against factor IX are reported. | 28 weeks after treatment start on on-demand treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic Effect of NNC-0156-0000-0009 When Used for Prophylaxis of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response | Haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4 point scale as excellent, good, moderate or poor. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures. Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours Poor - no improvement, or worsening of symptoms within 8 hours after two injections. The success rate and 95% confidence interval (CI) are reported here. | 52 weeks after treatment start for patients on prophylaxis | 
| Haemostatic Effect of NNC-0156-0000-0009 When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response | Haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4 point scale as excellent, good, moderate or poor. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures. Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single injection Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours Poor - no improvement, or worsening of symptoms within 8 hours after two injections. The success rate and 95% confidence interval (CI) are reported here. | 28 weeks after treatment start on on-demand treatment | 
| Number of Bleeding Episodes Per Patient During Routine Prophylaxis | The number of bleeding episodes per patient during routine prophylaxis was assessed using the individual annualised bleeding rates (spontaneous and traumatic bleeding episodes per patient per year). | 52 weeks after treatment start for patients on prophylaxis | 
| Factor IX Trough Levels | The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Lowest factor IX activity recorded during single-dose and steady state, immediately before next dose was given. The analysis was based on a mixed model on the log-transformed plasma factor IX activity with subject as a random effect. The estimated mean factor IX trough level was presented back-transformed to the natural scale. | 52 weeks after treatment start for patients on prophylaxis | 
| Incidence of Adverse Events (AEs) | The incidence of adverse events were summarised by the rate of AEs (number of AEs per patient years of exposure [PYE]). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration). | at 56 weeks ±2 weeks for patients on prophylaxis | 
| Incidence of Adverse Events (AEs) | The incidence of adverse events were summarised by the rate of AEs (number of AEs per PYE). Number of adverse events per PYE is number of adverse events /total time in trial. All adverse events reported are treatment emergent (any adverse events which occurred after trial product administration). | at 32 weeks ±2 weeks for patients on on-demand treatment | 
| Incidence of Serious Adverse Events (SAEs) | SAE was defined as an AE that resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. The incidence of SAEs were summarised by the rate of SAEs (number of SAEs per PYE). Number of SAEs per PYE is number of SAEs/total time in trial. All SAEs reported are treatment emergent (any serious adverse events which occurred after trial product administration). | at 56 weeks ±2 weeks for patients on prophylaxis | 
| Incidence of Serious Adverse Events (SAEs) | SAE was defined as an AE that resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. The incidence of SAEs were summarised by the rate of SAEs (number of SAEs per PYE). Number of SAEs per PYE is number of SAEs/total time in trial. All SAEs reported are treatment emergent (any serious adverse events which occurred after trial product administration). | at 32 weeks ±2 weeks for patients on on-demand treatment | 
| Host Cell Proteins (HCP) Antibodies | Subjects who were positive for anti-Host Cell Protein (HCP) antibodies. | 52 weeks after treatment start for patients on prophylaxis | 
| Host Cell Proteins (HCP) Antibodies | Subjects who were positive for anti-HCP antibodies. | 28 weeks after treatment start on on-demand treatment |