Haemophilia B
Conditions
Brief summary
The study investigates how well the medicine called nonacog beta pegol (N9-GP) works in Chinese people with haemophilia B. Participants will be treated with N9-GP. This is a medicine that doctors can already prescribe in other countries. The medicine will be injected into a vein (intravenous injection). At the visits to the clinic, the medicine will be injected by the study doctor. When treating themselves at home, participants inject the medicine using a needle and vial set. The study will last for about 12-16 months. The participants will have between 9 and 19 visits to the clinic and possibly also some phone calls with the study doctor. At all visits to the clinic, the participants will have blood samples taken.
Interventions
Nonacog beta pegol is administered as intravenous injections. Participants will receive nonacog beta pegol as prophylaxis, as on-demand for treatment of bleeding episodes and in relation to surgery.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male Chinese patient with moderate to severe congenital haemophilia B with a factor IX (FIX) activity less than or equal to 2 percent according to medical records. * Aged 12-70 years (both inclusive) at the time of signing informed consent. * History of at least 100 exposure days (EDs) to products containing FIX.1. * Patients currently on prophylaxis or patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months. * The patient, legally authorised representative (LAR) and/or caregiver are capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures.
Exclusion criteria
* Known or suspected hypersensitivity to trial product or related products. * Previous participation in this trial. Participation is defined as signed informed consent. * Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer. * Known history of FIX inhibitors based on existing medical records, laboratory report reviews and patient and LAR interviews. * Current FIX inhibitors greater than or equal to 0.6 Bethesda unit (BU). * HIV positive, defined by medical records, with CD4+ count less than or equal 200 per microlitre (μL) and a viral load greater than 200 particles per microlitre or greater than 400000 copies per millilitre (mL) within 6 months of the trial entry. If the data are not available in the medical records within the last 6 months, then the test must be performed at the screening visit. * Congenital or acquired coagulation disorder 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). * Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening. * Renal impairment defined as estimated glomerular filtration rate (eGFR) less than or equal to 30 mL/min/1.73 m\^2 for serum creatinine measured at screening. * Any disorder, except for conditions associated with haemophilia B, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol. * Platelet count less than 50×10\^9/L at screening. * Immune modulating or chemotherapeutic medication. * Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | From start of treatment (week 0) until end of treatment (up to week 50) | Haemostatic effect of N9-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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes | From start of treatment (week 0) until end of treatment (up to week 50) | The mean number of injections of N9-GP used for treatment of a bleed from start to stop of a bleed was reported and it was measured in international units per kilogram per bleed (IU/kg/bleed). |
| Consumption of Nonacog Beta Pegol for Prophylaxis (PPX) Treatment (Arm B Only) | From start of treatment (week 0) until end of treatment (week 50) | The mean consumption of N9-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year). |
| FIX Trough Levels During Prophylaxis (PPX) Treatment (Arm B Only) | From start of treatment (week 0) until end of treatment (week 50) | Trough levels of FVIII was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N9-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 participants as a random effect. The mean trough is presented back-transformed to the natural scale. The estimated mean/average steady state trough level of FVIII over time (all visits from start of treatment (week 0) until end of treatment) was presented. Data is reported for specific treatment in which participants were a part of at any time from week 0 to end of the treatment (EOT) Week 50, not at specific time points assessed from week 0 to EOT. |
| Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU) | From start of treatment (week 0) until end of treatment (week 50) | Number of participants who developed inhibitory antibodies (IA) 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. |
| Number of Adverse Events (AEs) | From start of treatment (week 0) until end of treatment (week 50) | 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 N9-GP administration. |
| Number of Treated Bleeding Episodes During Prophylaxis (PPX) Treatment (Arm B Only) | From start of treatment (week 0) until end of treatment (week 50) | Number of bleeding episodes per year data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year. |
| Incremental Recovery (IR) (Arm B Only) | Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12 | 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 international units per kilogram (IU/kg) body weight. FVIII activity was measured with a chromogenic assay. |
| Terminal Half-life (t½) (Arm B Only) | Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12 | Terminal half life was calculated as ln(2)/λz; where λz 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. |
| Clearance (CL) (Arm B Only) | Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12 | 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. |
| Area Under the Curve (AUC) (Arm B Only) | Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12 | Area under the plasma activity versus time profile from time zero to 168 hours (AUC0-168h) was measured. |
| Number of Serious Adverse Events (SAEs) | From start of treatment (week 0) until end of treatment (week 50) | 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). |
Countries
China
Participant flow
Recruitment details
This trial was conducted at 15 sites that enrolled participants in 1 country (China mainland).
Pre-assignment details
A total of 30 participants were exposed to trial products, of which 15 participants were in Arm A (on demand/Prophylaxis) treatment group and 15 in Arm B (Prophylaxis) treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Nonacog Beta Pegol (On-demand, Then Prophylaxis) Participants received intravenous injections of nonacog beta pegol (on-demand treatment for 28 weeks during treatment period 1, followed by 40 IU/kg for mild or moderate bleeds and 80 IU/kg for severe bleeds, with additional doses as needed if the initial treatment showed no effect during treatment period 2) until 30 exposure days (EDs) to nonacog beta pegol in the entire trial were fulfilled. | 15 |
| Arm B: Nonacog Beta Pegol (Prophylaxis) Participants received intravenous injections of 40 IU/kg nonacog beta pegol once weekly (prophylactic treatment with nonacog beta pegol at a dose of 40 IU/kg weekly) until 50 EDs (including treatment of breakthrough bleeds) and 50 weeks in the entire trial were fulfilled. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm B: Nonacog Beta Pegol (Prophylaxis) | Total | Arm A: Nonacog Beta Pegol (On-demand, Then Prophylaxis) |
|---|---|---|---|
| Age, Continuous | 26.9 Years STANDARD_DEVIATION 9.7 | 28.4 Years STANDARD_DEVIATION 8.7 | 29.9 Years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 30 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 30 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 30 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 12 / 15 | 4 / 14 | 14 / 15 |
| serious Total, serious adverse events | 1 / 15 | 0 / 14 | 0 / 15 |
Outcome results
Primary
Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX)
Haemostatic effect of N9-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.
Time frame: From start of treatment (week 0) until end of treatment (up to week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | None | 1 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (On-demand) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Excellent | 203 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (On-demand) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Moderate | 3 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (On-demand) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Good | 8 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (On-demand) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Missing | 0 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Good | 1 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Missing | 0 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Moderate | 0 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Excellent | 3 Bleeding Episodes |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | None | 0 Bleeding Episodes |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Missing | 0 Bleeding Episodes |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Good | 16 Bleeding Episodes |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Moderate | 1 Bleeding Episodes |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | None | 0 Bleeding Episodes |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Haemostatic Effect of Nonacog Beta Pegol When Used for Treatment of Bleeding Episodes During on Demand and Prophylaxis (PPX) | Excellent | 26 Bleeding Episodes |
Secondary
Area Under the Curve (AUC) (Arm B Only)
Area under the plasma activity versus time profile from time zero to 168 hours (AUC0-168h) was measured.
Time frame: Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12
Population: The PK analysis set included sub-set of participants from FAS who were included for PK assessments. Here, Number analysed (n) = Number of participants with available data for specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Area Under the Curve (AUC) (Arm B Only) | Week 0 | 51.856 hours*international units per milliliter | Geometric Coefficient of Variation 30.134 |
| Arm A: Nonacog Beta Pegol (On-demand) | Area Under the Curve (AUC) (Arm B Only) | Week 12 | 92.914 hours*international units per milliliter | Geometric Coefficient of Variation 21.725 |
Secondary
Clearance (CL) (Arm B Only)
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.
Time frame: Single-dose: 0-168 hours post injection at week 0, Steady-state: 0-168 hours post injection at week 12
Population: The PK analysis set included sub-set of participants from FAS who were included for PK assessments. Here, Number analysed (n) = Number of participants with available data for specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Clearance (CL) (Arm B Only) | Week 0 | 0.536 milliliters per hour per kilogram | Geometric Coefficient of Variation 22.143 |
| Arm A: Nonacog Beta Pegol (On-demand) | Clearance (CL) (Arm B Only) | Week 12 | 0.487 milliliters per hour per kilogram | Geometric Coefficient of Variation 26.552 |
Secondary
Consumption of Nonacog Beta Pegol for Prophylaxis (PPX) Treatment (Arm B Only)
The mean consumption of N9-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year).
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Consumption of Nonacog Beta Pegol for Prophylaxis (PPX) Treatment (Arm B Only) | 2212.3 IU/kg per year | Standard Deviation 26 |
Secondary
Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes
The mean number of injections of N9-GP used for treatment of a bleed from start to stop of a bleed was reported and it was measured in international units per kilogram per bleed (IU/kg/bleed).
Time frame: From start of treatment (week 0) until end of treatment (up to week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes | 42.4 IU/kg per bleed | Standard Deviation 1.1 |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes | 41.9 IU/kg per bleed | Standard Deviation 0.5 |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Consumption of Nonacog Beta Pegol for Treatment of Bleeding Episodes | 41.6 IU/kg per bleed | Standard Deviation 0.4 |
Secondary
FIX Trough Levels During Prophylaxis (PPX) Treatment (Arm B Only)
Trough levels of FVIII was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N9-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 participants as a random effect. The mean trough is presented back-transformed to the natural scale. The estimated mean/average steady state trough level of FVIII over time (all visits from start of treatment (week 0) until end of treatment) was presented. Data is reported for specific treatment in which participants were a part of at any time from week 0 to end of the treatment (EOT) Week 50, not at specific time points assessed from week 0 to EOT.
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | FIX Trough Levels During Prophylaxis (PPX) Treatment (Arm B Only) | 0.298 International unit per milliliter(IU/mL) |
Secondary
Incremental Recovery (IR) (Arm B Only)
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 international units per kilogram (IU/kg) body weight. FVIII activity was measured with a chromogenic assay.
Time frame: Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12
Population: The Pharmacokinetic (PK) analysis set included sub-set of subjects from FAS who were included for PK assessments. Number analysed = Number of participants with available data for specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Incremental Recovery (IR) (Arm B Only) | Week 12 | 0.0192 (IU/mL)/(IU/kg) | Geometric Coefficient of Variation 17.2668 |
| Arm A: Nonacog Beta Pegol (On-demand) | Incremental Recovery (IR) (Arm B Only) | Week 0 | 0.0182 (IU/mL)/(IU/kg) | Geometric Coefficient of Variation 18.955 |
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 N9-GP administration.
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the SAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Number of Adverse Events (AEs) | 29 Events |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Number of Adverse Events (AEs) | 6 Events |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Number of Adverse Events (AEs) | 29 Events |
Secondary
Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU)
Number of participants who developed inhibitory antibodies (IA) 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.
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU) | 0 Participants |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU) | 0 Participants |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Number of Participants With Inhibitory Antibodies Against FIX Defined as Titre ≥0.6 Bethesda Units (BU) | 0 Participants |
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).
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the SAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Number of Serious Adverse Events (SAEs) | 1 Events |
| Arm A: Nonacog Beta Pegol (Prophylaxis) | Number of Serious Adverse Events (SAEs) | 0 Events |
| Arm B: Nonacog Beta Pegol (Prophylaxis) | Number of Serious Adverse Events (SAEs) | 0 Events |
Secondary
Number of Treated Bleeding Episodes During Prophylaxis (PPX) Treatment (Arm B Only)
Number of bleeding episodes per year data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year.
Time frame: From start of treatment (week 0) until end of treatment (week 50)
Population: Results were based on the FAS which included all participants exposed to N9-GP in this trial.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Number of Treated Bleeding Episodes During Prophylaxis (PPX) Treatment (Arm B Only) | 3.12 bleeding episodes per year |
Secondary
Terminal Half-life (t½) (Arm B Only)
Terminal half life was calculated as ln(2)/λz; where λz 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.
Time frame: Single-dose: 30±10 minutes post injection at week 0, Steady-state: 30±10 minutes post injection at week 12
Population: The PK analysis set included sub-set of participants from FAS who were included for PK assessments. Here, Number analysed (n) = Number of participants with available data for specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Nonacog Beta Pegol (On-demand) | Terminal Half-life (t½) (Arm B Only) | Week 0 | 90.868 hour | Geometric Coefficient of Variation 13.535 |
| Arm A: Nonacog Beta Pegol (On-demand) | Terminal Half-life (t½) (Arm B Only) | Week 12 | 90.738 hour | Geometric Coefficient of Variation 21.581 |