Congenital Bleeding Disorder, Haemophilia A
Conditions
Brief summary
This trial is conducted in Asia, Europe, and North and South America. The trial consists of a main trial and a sub-trial. The main trial investigates safety and efficacy of turoctocog alfa (recombinant factor VIII, rFVIII (N8)) in haemophilia A subjects, while the sub-trial investigates safety and efficacy of turoctocog alfa in prevention and treatment of bleeding episodes during surgical procedures.
Interventions
DRUGturoctocog alfa
Subjects will receive bleeding preventive treatment (home treatment with self-injection i.v.) with turoctocog alfa at a dose of 20-40 IU/kg body weight every second day or 20-50 IU/kg body weight three times per week at the investigator's discretion.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male subjects with the diagnosis of severe (FVIII less than or equal to 1%) haemophilia A from age 12 (except for Israel where the age limit will be 18 for the first 10 subjects recruited in the trial) to 56 years having a weight of 10 to 120 kg * Documented history of at least 150 exposure days to any other FVIII products (prevention or treatment of bleeds) * No history of FVIII inhibitors greater than or equal to 0.6 BU/mL. The inhibitor should be measured regularly for at least the last 8 years or since the first treatment of haemophilia A * No detectable inhibitors to FVIII (greater than or equal to 0.6 BU/mL) (as assessed by a Central Laboratory at the time of screening)
Exclusion criteria
* Congenital or acquired coagulation disorders other than haemophilia A * Creatinine levels 50% above normal level (as defined by central laboratory range) * Known or suspected allergy to trial product (N8) or related products
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 188 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 188 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 AEs: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, persistent/significant disability/incapacity/congenital anomaly/birth defect. |
Countries
Brazil, Croatia, Denmark, Germany, Hungary, Israel, Italy, Japan, Malaysia, Russia, Serbia, Serbia and Montenegro, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The patients were recruited at 48 sites in 15 countries: Republic of Serbia (5), Turkey (5), Germany (4), Japan (8), the United Kingdom (3) and the United States of America (10). Two sites each in Brazil, Italy, Spain and Croatia. One site each in Switzerland, Taiwan, Israel, Malaysia and Russian Federation.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Treated With Turoctocog Alfa All subjects participating in the study (Part A + Part B + Part C). | 150 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | All Subjects Treated With Turoctocog Alfa |
|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 11.79 |
| Race/Ethnicity, Customized Hispanic Or Latino | 25 participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 125 participants |
| Region of Enrollment Brazil | 16 participants |
| Region of Enrollment Croatia | 11 participants |
| Region of Enrollment Germany | 10 participants |
| Region of Enrollment Israel | 12 participants |
| Region of Enrollment Italy | 7 participants |
| Region of Enrollment Japan | 9 participants |
| Region of Enrollment Malaysia | 5 participants |
| Region of Enrollment Russia | 5 participants |
| Region of Enrollment Serbia | 19 participants |
| Region of Enrollment Spain | 4 participants |
| Region of Enrollment Switzerland | 5 participants |
| Region of Enrollment Taiwan | 4 participants |
| Region of Enrollment Turkey | 11 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 150 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 150 |
| serious Total, serious adverse events | 7 / 150 |
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 188 days per subject.
Population: The safety analysis set includes all 150 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 148 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 AEs: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, persistent/significant disability/incapacity/congenital anomaly/birth defect.
Time frame: The adverse events were collected throughout the trial, corresponding to an average of 188 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 | 222 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Severe AEs | 8 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Moderate AEs | 51 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Mild AEs | 163 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Serious AEs | 9 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Probably or Possibly Related | 17 events |
| Part C | Frequency of Adverse Events (AEs) | Probably or Possibly Related | 0 events |
| Part C | Frequency of Adverse Events (AEs) | All AEs | 3 events |
| Part C | Frequency of Adverse Events (AEs) | Mild AEs | 2 events |
| Part C | Frequency of Adverse Events (AEs) | Serious AEs | 0 events |
| Part C | Frequency of Adverse Events (AEs) | Severe AEs | 0 events |
| Part C | Frequency of Adverse Events (AEs) | Moderate AEs | 1 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Severe AEs | 8 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Moderate AEs | 52 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Probably or Possibly Related | 17 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Mild AEs | 165 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | All AEs | 225 events |
| All Subjects Treated With Turoctocog Alfa | Frequency of Adverse Events (AEs) | Serious AEs | 9 events |