Congenital Bleeding Disorder, Haemophilia A
Conditions
Brief summary
This trial is conducted in Asia, Europe, and North and South America. The aim of this clinical trial is to investigate the safety and efficacy of turoctocog alfa (recombinant factor VIII, rFVIII (N8)) in male previously treated paediatric subjects with haemophilia A.
Interventions
DRUGturoctocog alfa
Subjects will be treated 3 times per week or every second day with intravenous injections of turoctocog alfa. The dose range for preventive treatment is 25-60 IU/kg body weight depending on treatment regimen.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male patients with severe (baseline FVIII less than or equal to 1%) haemophilia A * Age below 12 years and weight at least 11 kg
Exclusion criteria
* Surgery planned to occur during trial participation (exceptions are port placement, dental extractions, and minor, uncomplicated emergent procedures) * Congenital or acquired coagulation disorders other than haemophilia A * Any history of FVIII inhibitors (greater than or equal to 0.6 BU/mL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)) | The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject. | The incidence rate of FVIII inhibitors was calculated by including all patients with inhibitors in the nominator and including all patients with a minimum 50 exposure plus any patients with less than 50 exposures but with inhibitors in denominator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events (AEs) | The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject | Adverse event was defined as events occurring after administration of trial product. Severe AEs: considerable interference with subject's daily activities, unacceptable. Moderate AEs: Marked symptoms, moderate interference with the patient's daily activities. Mild AEs: No or transient symptoms, no interference with the patient's daily activities. Serious AE: AE that at any dose results 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. |
Countries
Brazil, Italy, Japan, Lithuania, Malaysia, North Macedonia, Poland, Puerto Rico, Russia, Serbia, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
Of a total of 39 initiated trial sites, 26 sites enrolled and dosed at least one patient. The country distribution was as follows: Brazil (3), Italy (1), Lithuania (1), Macedonia (1), Malaysia (1), Poland (2), Russia (2), Serbia (1), Taiwan (1), Turkey (3) and the United States of America (10).
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Treated With Turoctocog Alfa The patients received bleeding preventive treatment with a single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly. Turoctocog alfa was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Pharmacokinetic assessments were performed in at least 13 patients from each age cohort. Each patient participating in the pharmacokinetic assessments received one dose of previous factor VIII (FVIII) and one dose of turoctocog alfa. | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Subjects Treated With Turoctocog Alfa |
|---|---|
| Age, Continuous | 6.08 years STANDARD_DEVIATION 2.91 |
| Race/Ethnicity, Customized Hispanic or Latino | 16 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 47 participants |
| Region of Enrollment Brazil | 9 participants |
| Region of Enrollment Italy | 2 participants |
| Region of Enrollment Lithuania | 4 participants |
| Region of Enrollment Macedonia, The Former Yugoslav Republic of | 5 participants |
| Region of Enrollment Malaysia | 5 participants |
| Region of Enrollment Poland | 5 participants |
| Region of Enrollment Russia | 8 participants |
| Region of Enrollment Serbia | 5 participants |
| Region of Enrollment Taiwan | 1 participants |
| Region of Enrollment Turkey | 7 participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 63 |
| serious Total, serious adverse events | 3 / 63 |
Outcome results
Primary
The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU))
The incidence rate of FVIII inhibitors was calculated by including all patients with inhibitors in the nominator and including all patients with a minimum 50 exposure plus any patients with less than 50 exposures but with inhibitors in denominator.
Time frame: The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject.
Population: The safety analysis set includes all 63 subjects who received at least one dose of the investigational product. The analysis of the primary endpoint included all subjects with at least 50 exposure days and/or with inhibitors. A total of 59 subjects had 50 exposure days (EDs).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Subjects Treated With Turoctocog Alfa | The Incidence Rate of FVIII Inhibitors (Greater Than or Equal to 0.6 Bethesda Units (BU)) | 0 N with Inhibitors / N with ≥50 EDs |
Secondary
Frequency of Adverse Events (AEs)
Adverse event was defined as events occurring after administration of trial product. Severe AEs: considerable interference with subject's daily activities, unacceptable. Moderate AEs: Marked symptoms, moderate interference with the patient's daily activities. Mild AEs: No or transient symptoms, no interference with the patient's daily activities. Serious AE: AE that at any dose results 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.
Time frame: The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject
Population: Safety analysis set includes all subjects who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | All AEs | 86 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Severe AEs | 0 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Moderate AEs | 11 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Mild AEs | 74 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Serious AEs | 3 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Probably or possibly related | 2 events |