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

Phase 3

Completed

Conditions: Haemophilia B
Congenital Bleeding Disorder

Interventions: Drug: nonacog beta pegol

Registration Number: NCT01333111

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 74

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylaxis, low dose (trial duration 52 weeks)	nonacog beta pegol	-
Prophylaxis, high dose (trial duration 52 weeks)	nonacog beta pegol	-
On-demand (trial duration 28 weeks)	nonacog beta pegol	-

Primary Outcome Measures

Name	Time	Method
Incidence of Inhibitory Antibodies Against Factor IX Defined as Titre Equal to or Above 0.6 BU (Bethesda Units)	28 weeks after treatment start on on-demand treatment	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.

Secondary Outcome Measures

Name	Time	Method
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	52 weeks after treatment start for patients on prophylaxis	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.
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	28 weeks after treatment start on on-demand treatment	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.
Number of Bleeding Episodes Per Patient During Routine Prophylaxis	52 weeks after treatment start for patients on 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).
Factor IX Trough Levels	52 weeks after treatment start for patients on prophylaxis	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.
Incidence of Serious Adverse Events (SAEs)	at 32 weeks ±2 weeks for patients on on-demand treatment	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).
Host Cell Proteins (HCP) Antibodies	28 weeks after treatment start on on-demand treatment	Subjects who were positive for anti-HCP antibodies.
Incidence of Adverse Events (AEs)	at 32 weeks ±2 weeks for patients on on-demand treatment	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).