Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B: An Extension to Trials NN7999-3747 and NN7999-3773

Phase 3

Completed

Conditions: Congenital Bleeding Disorder
Haemophilia B

Interventions: Drug: nonacog beta pegol

Registration Number: NCT01395810

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Asia, Europe, Japan, North America and South Africa. The aim is to evaluate the safety and efficacy of nonacog beta pegol (NNC-0156-0000-0009) after long-term exposure in patients with haemophilia B.

This trial is an extension to trials NN7999-3747 (NCT01333111/paradigm™ 2) and NN7999-3773 (NCT01386528/paradigm™ 3).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 71

Inclusion Criteria

Previous participation in NN7999-3747 (NCT01333111) and/or NN7999-3773

Exclusion Criteria

Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR (legal acceptable representative) interviews
Current FIX inhibitors above or equal to 0.6 BU (Bethesda Units)
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)
Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator's (trial physician) judgement, could imply a potential hazard to the patient, interfere with trial participation, or interfere with trial outcome

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylaxis, high dose (every second week)	nonacog beta pegol	-
Prophylaxis, high dose (once weekly)	nonacog beta pegol	-
Prophylaxis, low dose (once weekly)	nonacog beta pegol	-
On-demand	nonacog beta pegol	-

Primary Outcome Measures

Name	Time	Method
Incidence of Inhibitory Antibodies Against FIX Defined as Titre Above or Equal to 0.6 BU (Bethesda Units)	From Day 1 up to 2 years	The primary endpoint was incidence of inhibitors against coagulation factor nine (FIX) defined as titre ≥0.6 Bethesda unit (BU). Number of subjects who developed inhibitors against FIX are reported.

Secondary Outcome Measures

Name	Time	Method
Number of Bleeding Episodes During Routine Prophylaxis	From Day 1 up to 2 years	Annualized bleeding rate is the total number of bleeding episodes/total exposure time. It is analysed by a Poisson regression model with dose as a factor allowing for over-dispersion and using treatment duration as an offset. Median annualized bleeding rate is the median of individual annualized bleeding rates. Numbers are based on the treatment arm at the time of each bleed.
FIX Trough Levels	From Day 1 up to 2 years	During the trial, the pre-dose FIX levels was measured with the one-stage clotting assay. Measurements taken at least 5 days and no more than 10 days after last dose as well as at least 14 days after last bleeding episode were included in this analysis. The mean FIX trough levels were estimated based on the mixed effects model on the log-transformed plasma concentration with subject as a random effect. The mean FIX trough level was presented back-transformed to the natural scale.
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes, Assessed as Success/Failure Based on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate, Poor)	From Day 1 up to 2 years	The haemostatic effect was evaluated by a four-point scale where an "excellent" or "good" outcome translated into a successful treatment, and a "moderate" or "poor" outcome was considered a treatment failure. The values mentioned below do not include bleeds with missing response.
Incidence of Adverse Events (AEs)	From Day 1 up to 2 years	AEs were summarized by frequency of events and frequency of patients with any event. Incidence of AEs was expressed as number of AEs per subject years of exposure (total number of events /total time in trial).
Incidence of Serious Adverse Events (SAEs)	From Day 1 up to 2 years	AEs were summarized by frequency of events and frequency of patients with any event. Incidence of serious AEs was expressed as number of serious AEs per subject years of exposure (total number of events /total time in trial).