Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A

Phase 3

Completed

Conditions: Haemophilia A
Congenital Bleeding Disorder

Interventions: Drug: turoctocog alfa

Registration Number: NCT01493778

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Asia, Europe and North America. The purpose of the trial is to evaluate the safety and efficacy of turoctocog alfa in prevention and treatment of bleeds in previously untreated children with haemophilia A.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 60

Inclusion Criteria

Age below 6 years
Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)
Male patients diagnosed with congenital severe haemophilia A (FVIII level equal to or below 1%)
No prior use of purified clotting factor products (previous exposure, equal to or less than 5 ED to blood components, e.g. cryoprecipitate, fresh frozen plasma, is accepted) including commercially available NovoEight® /Novoeight®

Exclusion Criteria

Known or suspected allergy to hamster protein or intolerance to trial product(s) or related products
Previous participation in this trial defined as withdrawal after administration of trial product
Congenital or acquired coagulation disorders other than haemophilia A
Any history of Factor VIII inhibitor
Ongoing treatment or planned treatment during the trial with immunomodulatory agents (e.g. intravenous immunoglobulin (IVIG), routine systemic corticosteroids)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
turoctocog alfa	turoctocog alfa	-

Primary Outcome Measures

Name	Time	Method
Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial	From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day)	The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.

Secondary Outcome Measures

Name	Time	Method
Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	The haemostatic effect of turoctocog alfa was summarised by frequency tables containing count of all bleeds and assessed on a predefined four point scale: Excellent, Good, Moderate and None. The analysis was based on the total number of bleeds and their response to treatment. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Annualised Bleeding Rate (ABR)	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Annualised bleeding rate defined as number of bleeds in total per patient per year following treatment were estimated by a Poisson model allowing for over-dispersion. The Poisson estimate is presented with a 95% confidence interval (CI). The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Number of Turoctocog Alfa (N8) Injections Required Per Bleed	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	The number of injections of turoctocog alfa (N8) required per bleed was calculated as the number of injections of turoctocog alfa used in the time period from start of the bleed to stop of the bleed. The mean number of turoctocog alfa injections required to stop the bleed is presented. The analysis was based on the total number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per month. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per year. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Mean consumption of turoctocog alfa (N8) used for treatment of bleed from start to stop of bleed. The analysis was based on number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Mean consumption of turoctocog alfa (N8) used for preventive treatment per month per patient. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Number of adverse events and serious adverse events per patient years of exposure. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial (exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level)	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	The incidence rates (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of clinically relevant inhibitors were defined as an inhibitor titre (≥ 0.6 BU) combined with a decreased recovery (\<66% of expected level). Incidence rate of clinically relevant inhibitors according to the type of assay used is presented. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).
Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL)	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Incidence rate (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of high-titre inhibitors defined as inhibitor titre ≥ 5 BU (Bethesda Units)/mL). The inhibitors were evaluated for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).
Change in Total Scores for Parent Reported Treatment Satisfaction	Visit 3 (10th-15th ED); Visit 5 (50th-55th ED); End of trial (within 8 weeks of their last scheduled visit in the extension phase)	The caregivers/parent reported treatment satisfaction is assessed by the parents using the haemophilia satisfaction questionnaire (HEMO-SAT). The questionnaire contained questions related to treatment that covered 6 domains (ease and convenience, efficacy, burden, specialist, centre and general satisfaction). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. The scores of the domains at visit 3 (10th-15th ED), visit 5 (50th-55th ED) and end of trial (EoT) are presented.
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient)	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Resource utilisation and caregiver burden are analysed in terms of average number of days absent from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient)	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial	Resource utilisation and caregiver burden are analysed in terms of average number of days of absence from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 \[50-55 exposure day\], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.