Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Number of Bleeding Episodes Per Year (Annualised Bleeding Rate) |
Number of bleeding episodes per year (Annualised Bleeding Rate) data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year. |
From start of treatment (Week 0) until Week 28 |
|
Secondary |
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None) |
Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms. |
From start of treatment (Week 0) until Week 28 |
|
Secondary |
Number of Injections Needed to Treat Bleeding Episodes |
The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed was reported. |
From start of treatment (Week 0) until Week 28 |
|
Secondary |
Consumption of N8-GP for Prophylaxis |
The mean consumption of N8-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year). |
From start of treatment (Week 0) until Week 28 |
|
Secondary |
FVIII Trough Activity During Prophylaxis |
Trough levels of FVIII was reported for all participnats who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator. The analysis is based on a mixed model on the log transformed plasma FVIII activity with age group as fixed effect and participant as a random effect. The mean trough is presented back-transformed to the natural scale. |
From start of treatment (Week 0) (excluding the first exposure) until Week 28 |
|
Secondary |
Percentage of Participants With Incidence Rate of Confirmed FVIII Inhibitors =0.6 BU |
Percentage of participants who developed inhibitory antibodies against FVIII was presented. A participant was said to have FVIII-inhibitors if two consecutive tests, preferably within 2 weeks, were positive (greater than or equal to (=) 0.6 bethesda unit (BU)). For the calculation of the inhibitor rate the numerator was included for all participants with neutralising antibodies while the denominator was included for all participants with a minimum of 50 exposures plus any participants with less than 50 exposures but with neutralising inhibitor. |
From start of treatment (Week 0) until Week 28 |
|
Secondary |
Number of Adverse Events (AEs) |
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All presented AEs are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration. |
From start of treatment (Week 0) until end of trial (Week 32) |
|
Secondary |
Number of Serious Adverse Events (SAEs) |
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. All presented SAEs are treatment-emergent (any serious adverse events which occurred after trial product administration). |
From start of treatment (Week 0) until end of trial (Week 32) |
|
Secondary |
Incremental Recovery (IR) |
The incremental recovery was calculated by subtracting the FVIII activity (IU/mL) measured in plasma at time 0 from that measured at time 30 min after dosing and dividing this difference by the dose injected at time 0 expressed as IU/kg body weight. FVIII activity was measured with a chromogenic assay. |
30 min post-injection at Week 0, Week 28 |
|
Secondary |
FVIII Activity 30 Min Post-injection (C30min) |
FVIII plasma activity was measured after 30 mins of injection. FVIII activity was measured with a chromogenic assay. |
30 min post-injection at Week 0, Week 28 |
|
Secondary |
FVIII Trough Activity 96 h Post-injection (C96h) |
FVIII plasma activity was measured after 96 h of injection. This was measured at two time points Week 0 and Week 28 during the study. Chromogenic assay was performed. |
Single-dose: 96 h ± 8 h post-injection at Week 0, Steady-state: 96 h ± 8 h post-injection at Week 28 |
|
Secondary |
Area Under the Curve (AUC0-inf) |
Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured. |
0-96 hours post-injection at Week 0 and Week 28 |
|
Secondary |
Area Under the Curve (0-t) |
Area under the plasma activity versus time profile from time zero to last measurable activity (AUC0-t) was measured. |
0-96 hours post-injection at Week 0 and Week 28 |
|
Secondary |
Area Under the Curve (0-96h) |
Area under the plasma activity versus time profile from time zero to 96 hours (AUC0-96h) was measured. |
0-96 hours post-injection at Week 0 and Week 28 |
|
Secondary |
Accumulation Ratio |
Accumulation ratio was calculated as AUC(0-96h) at steady state/AUC(0-96h) at single dose. AUC(0-96) is the area under the plasma activity versus time profile from time zero to 96 hours. |
0-96 hours post-injection on Week 28 |
|
Secondary |
Terminal Half-life (t½) |
Terminal half life was calculated as ln(2)/?z; where ?z is the terminal elimination rate constant. The terminal elimination rate constant was estimated using linear regression on the terminal part of the log (activity) versus time profile. |
0-96 hours post-injection on Week 0 and Week 28 |
|
Secondary |
Clearance (CL) |
Clearance (CL) of drug after intravenous administration was reported. Clearance was calculated using the formula CL= Dose / AUC(0-inf) for single dose and CL= Dose / AUC(0-96) h for steady state. |
Single-dose: 0-96 h post-injection at Week 0, Steady-state: 0-96 h post-injection at Week 28 |
|
Secondary |
Apparent Volume of Distribution (Vz) Based on the Terminal Phase |
Apparent volume of distribution (Vz) based on the terminal phase was measured. Apparent volume of distribution was calculated using formula: total plasma clearance divided by terminal elimination rate constant (Vz= CL/?z). |
0-96 hours post-injection on Week 0 and Week 28 |
|
Secondary |
Apparent Volume of Distribution (Vss) Based on Steady-state |
Apparent volume of distribution (Vss) at steady-state was measured. Apparent volume of distribution (Vss) was calculated using formula: total plasma clearance multiplied by mean residence time (Vss=CL*MRT). |
0-96 h post-injection at Week 28 |
|
Secondary |
Extrapolated Area Under the Curve (AUC Percent [%] Extrap |
Percentage of AUC(0-inf) determined by extrapolation. It was calulating using formula: Area under the plasma activity versus time profile from given measurable time to infinity (AUCt-inf)/Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf). |
0-96 hours post-injection on Week 0 and Week 28 |
|
Secondary |
Mean Residence Time |
Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC [0-inf]) divided by AUC (0-inf). (AUMC [0-inf]) is the area under the first moment plasma concentration-time curve from time 0 to infinity. |
0-96 hours post-injection on Week 0 and Week 28 |
|
Secondary |
Terminal Elimination Rate Constant (?z) |
The terminal elimination rate constant was estimated using linear regression on the terminal part of the log(activity) versus time profile. |
0-96 hours post-injection on Week 0 and Week 28 |
|