Congenital Bleeding Disorder, Haemophilia B
Conditions
Brief summary
This trial is conducted in Asia, Europe and North America. The aim of the trial is to evaluate safety, efficacy and pharmacokinetics (the exposure of the trial drug in the body) of NNC-0156-0000-0009 (nonacog beta pegol, N9-GP) in previously treated children with Haemophilia B.
Interventions
A single dose of 40 U/kg will be administered intravenously, i.v. (into the vein) once weekly.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
0 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male patients with moderately severe or severe congenital haemophilia B with a Factor IX activity level below or equal to 2% according to medical records * Age below or equal to 12 years (until patient turns 13 years, at time of inclusion) * Body weight above or equal to 10 kg * History of at least 50 exposure days (EDs) to other FIX products * The patient and/or parent(s)/caregiver are capable of assessing a bleeding episode, keeping an electronic diary (eDiary), capable of conducting home treatment and otherwise able to follow trial procedures
Exclusion criteria
* Known history of FIX inhibitors * Current FIX inhibitors above or equal to 0.6 Bethesda Units (BU) * Congenital or acquired coagulation disorder other than haemophilia B * Platelet count below 50,000/mcL at screening * Alanine aminotransferase (ALT) above 3 times the upper limit of normal reference ranges at screening * Creatinine level above or equal to 1.5 times above the upper normal limit of normal reference ranges at screening * Human immunodeficiency virus (HIV) positive, defined by medical records, and with a CD4+ lymphocyte count below or equal to 200/mcL * Immune modulating or chemotherapeutic medication (except single pulse treatment, inhaled and topical steroids) * Previous arterial thrombotic events (myocardial infarction and intracranial thrombosis, as defined by medical records)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) | From week 0 to week 52 | Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of participants who developed inhibitory antibodies against factor IX are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) | From week 0 to EOT (approximately week 544) | Description of the haemostatic effect of nonacog beta pegol when used for treatment of bleeding episodes was measured and listed according to the four point scale for haemostatic response as below: 1. Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single infusion. 2. Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection. 3. Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one infusion within 8 hours. 4. Poor - no improvement, or worsening of symptoms within 8 hours after two injections. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures. |
| Incremental Recovery at 30 Minutes (IR30min) | Week 0 (30 minutes after first exposure) | The incremental recovery was calculated by dividing the baseline-subtracted factor IX activity Units per milliliter (U/mL) measured in plasma 30 min after dosing by the dose injected at time 0 expressed as units per kilogram (U/kg) body weight. |
| Trough Level (Single-dose ) | Week 0 (one week after first exposure) | The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Geometric mean of the lowest activity of factor IX recorded at week 0 (immediately before next dose was given). |
| Terminal Half-life (t1/2) | Week 0 (30 minutes until one week after first exposure) | Terminal half life is presented at week 0, 30 minutes until one week after first exposure. |
| Trough Level (Steady State) | From week 4 to EOT (approximately week 544) | The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. The estimated mean of the lowest activity recorded immediately before next dose was given from week 4 to EOT approximately (week 544). Data is reported for specific age groups in which participants were a part of at any time from week 4 to EOT, not at specific time points assessed from week 4 to EOT. The analysis is based on a mixed model on the log-transformed plasma concentrations with participant as a random effect and the mean trough level is presented back-transformed to the natural scale. Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Number of Adverse Events | Week 0 to EOT (approximately week 544) | An adverse event (AE) was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Here, data is presented for all adverse events (serious adverse events and other adverse events) from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Number of Serious Adverse Events (SAEs) | Week 0 to EOT (approximately week 544) | A SAE was an experience that at any dose resulted in any of the following: death, a life-threatening experience a), In-patient hospitalisation or prolongation of existing hospitalisation b) a persistent or significant disability/incapacity c) a congenital anomaly/birth defect, Important medical events d) that did not result in death, were life-threatening a) or required hospitalization. Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Medical Events of Special Interest (MESI) | Week 0 to EOT (approximately week 544) | The following events were defined as MESIs: -Medication errors concerning trial products, -Administration of wrong drug, * Wrong route of administration, * Administration of a high dose with the intention to cause harm, e.g. suicide attempt, * Administration of an accidental overdose: more than 20 % from the intended dose, * Inhibitor formation against factor IX (FIX), * Thromboembolic events, * Anaphylactic reaction. * Allergic reaction including, but not limited to, any acute immunoglobulin E (IgE) mediated reaction or delayed type hypersensitivity. Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Development of Host Cell Protein (HCP) Antibodies | From week 0 to EOT (approximately week 544) | Participants were examined for the development of antibodies against HCP. Number of participants who developed antibodies against HCP is presented. |
| FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes | From week 0 to EOT (approximately week 544) | Consumption of nonacog beta pegol for treatment of bleeding episodes International units per kilogram per year (IU/Kg/year) per participant is presented from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes | From week 0 to EOT (approximately week 544) | Average dose of nonacog beta pegol for treatment of bleed from start to stop of bleed is presented from week 0 to EOT approximately (week 544) in international units per kilogram per bleed (IU/Kg/bleed). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes | From week 0 to EOT (approximately week 544) | Number of doses of FIX consumed for the treatment of bleeding episodes is presented from week 0 to EOT approximately (week 544). Here, data of number of doses of FIX for the treatment of bleeding episodes is reported among all the participants in an arm. Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure. |
| Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168)) | 0-168 hours post-dosing at week 0 | Area under the curve activity versus time profile from time zero to 168 hours post dose of nonacog beta pegol is presented. |
| Number of Bleeding Episodes During Prophylaxis | From week 0 to EOT (approximately week 544) | The number of bleeding episodes per participant during routine prophylaxis was assessed using the individual annualised bleeding rates (bleeding episodes per participant per year). |
| Mean Residence Time (MRT) | 0-168 hours post-dosing at week 0 | Mean residence time (MRT) of nonacog beta pegol after single dose is presented. |
| Volume of Distribution at Steady State (Vss) | 0-168 hours post-dosing at week 0 | Volume of distribution at steady state (Vss) of nonacog beta pegol is presented. |
| FIX Activity at 30 Minutes (C30min) (Single Dose) | 30 min post-dosing at week 0 | FIX activity (international units per milliliter (IU/mL)) at 30 minutes after single dose is presented. |
| FIX Activity at 30 Minutes (C30min) (Steady State) | 30 min post-dosing from week 4 to EOT (approximately week 544) | Mean FIX activity at 30 minutes post-dosing from week 4 to EOT approximately (week 544) (C30min) (steady state) is presented. |
| TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (Week -6), week 52, week 176 approximately (visit 17) | The Dutch institute of Prevention and Health and the Leiden University Hospital (TNO-AZL) preschool quality of life clustered into 12 multi-item scales is used to assess the health-related quality of life, such as children's motor, communication, emotions, and body structure. Suitable for children from 6 months to 6 years old (TAPQOL). Parents fill in according to the child's condition. Higher score (range 0-100) represents better outcome. The scale range for each of 12 multi-item scales was (0-100) with high score representing better outcome. In this study, the TAPQOL was assessed for children of age 0-3 years. |
| Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation | From week 0 to EOT (approximately week 544) | Number of participants with health economic impact of N9-GP treatment through characterisation of general hospitalisation is presented. Number of participants hospitalised for 0 & 1 day is presented. |
| Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation | From week 0 to EOT (approximately week 544) | Health economic impact of N9-GP treatment is presented through number of intensive care hospitalization days. |
| Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | From week 0 to EOT (approximately week 544) | Health economic impact of N9-GP treatment through number of days bleedings caused missing school or studies. Number of participants who missed school or studies for 0,1 and 2 days are presented. |
| Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids | From week 0 to EOT (approximately week 544) | Health economic impact of N9-GP treatment through number of days the patient used mobility aids (wheelchair and/or crutches) is presented. |
| Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work | From week 0 to EOT (approximately week 544) | Health economic impact of N9-GP treatment through number of days bleeding caused parents to miss work is presented from week 0 to EOT approximately (week 544). |
| Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6), week 52, EOT (approximately week 544) | Haemophilia quality of life clustered into 11 multi-item scale which is used to assess haemophilia related quality of life such as children's physical health, feeling, family, friends, sport, treatment, dealing with haemophilia, view of a patient. Here, HAEMO-QOL was assessed for the children of age group 8-12 years. The scale range for each of 11 multi-item scale was 0-100 with high scores indicating low quality of life. Multi-item scores and total score were calculated using the following formula: 1/4(Sum of answered items / number of answered items - 1) x 100. HAEMO-QOL scores range from a 0 to 100 scale where high scores (nearing 100) indicate a low quality of life rating. |
| Hemophilia Treatment Satisfaction (HEMO-SAT) | Screening (Week -6), week 176 (visit 17) | Haemophilia treatment satisfaction change from baseline (screening week -6) to week 176 (visit 17) is presented. The treatment satisfaction of a bleed with N8-GP was assessed using HEMO-SAT assessment tool which contains a questionnaire with 6 domains (Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction). The scale range for each 6 domains was (0-100) with lower score indicating higher treatment satisfaction. HEMO-SAT was assessed for the children of age group 4-7 years and 8-12 years. Domain score and total score were calculated using following formula - 1/4 (sum of answered items / Number of answered item - 1) x 100. HEMO-SAT scores range from 0-100, where low scores reflecting greater treatment satisfaction. |
| Clearance (CL) | 0-168 hours post-dosing at week 0 | Clearance of nonacog beta pegol after single dose is presented. |
Countries
Brazil, Canada, Croatia, France, Germany, Italy, Japan, Malaysia, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Of the 19 sites that screened participants, 17 sites enrolled participants. The trial was therefore conducted at 17 sites in 8 countries, as follows: Canada: 1 site; Germany: 1 site; Italy: 1 site; Japan: 3 sites; Malaysia: 1 site; Taiwan: 1 site; United Kingdom: 3 sites; United States: 6 sites
Pre-assignment details
The trial was divided into a 52-week main phase where patients received prophylaxis treatment until 50 EDs (Exposure days), followed by an extension phase.
Participants by arm
| Arm | Count |
|---|---|
| Younger Children (0-6 Years) Participants received nonacog beta pegol 40 U/kg I.V. once weekly for 52 weeks in main phase and extension phase till end of trial. Bleeding episodes were treated as soon as they were identified. The dose for treatment of an uncomplicated mild/moderate bleeding episode, e.g. a joint bleed, was a single dose of nonacog beta pegol 40 U/kg I.V. Severe bleeding episodes were treated immediately with 80 U/kg. | 12 |
| Older Children (7-12 Years) Participants received nonacog beta pegol 40 U/kg I.V. once weekly for 52 weeks in main phase and extension phase till end of trial. Bleeding episodes were treated as soon as they were identified. The dose for treatment of an uncomplicated mild/moderate bleeding episode, e.g. a joint bleed, was a single dose of nonacog beta pegol 40 U/kg I.V. Severe bleeding episodes were treated immediately with 80 U/kg. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not continuing in extension phase | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
| Overall Study | Withdrawal during extension phase,- Non-compliance | 0 | 1 |
| Overall Study | Withdrawal during extension phase, Other | 3 | 3 |
| Overall Study | Withdrawal during extension phase, Withdrawal criteria | 0 | 2 |
| Overall Study | Withdrawal during extension phase, Withdrawal of consent | 2 | 1 |
Baseline characteristics
| Characteristic | Younger Children (0-6 Years) | Older Children (7-12 Years) | Total |
|---|---|---|---|
| Age, Continuous | 3.1 years STANDARD_DEVIATION 1.7 | 9.6 years STANDARD_DEVIATION 1.6 | 6.5 years STANDARD_DEVIATION 3.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 11 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 23 | 0 / 14 | 0 / 6 |
| other Total, other adverse events | 11 / 12 | 20 / 23 | 12 / 14 | 4 / 6 |
| serious Total, serious adverse events | 2 / 12 | 4 / 23 | 1 / 14 | 0 / 6 |
Outcome results
Primary
Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)
Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of participants who developed inhibitory antibodies against factor IX are reported.
Time frame: From week 52 to End of trial (EOT) (approximately week 544)
Population: Safety analysis set (SAS) included all participants exposed to nonacog beta pegol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Younger Children (0-6 Years) | Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) | 0 Participants |
| Older Children (7-12 Years) | Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) | 0 Participants |
Primary
Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)
Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of participants who developed inhibitory antibodies against factor IX are reported.
Time frame: From week 0 to week 52
Population: Safety analysis set (SAS) included all participants exposed to nonacog beta pegol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Younger Children (0-6 Years) | Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) | 0 Participants |
| Older Children (7-12 Years) | Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) | 0 Participants |
Secondary
Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168))
Area under the curve activity versus time profile from time zero to 168 hours post dose of nonacog beta pegol is presented.
Time frame: 0-168 hours post-dosing at week 0
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168)) | 37.764 Units*hour per milliliter (U*h/mL) | Standard Deviation 4.586 |
| Older Children (7-12 Years) | Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168)) | 44.192 Units*hour per milliliter (U*h/mL) | Standard Deviation 7.3 |
Secondary
Clearance (CL)
Clearance of nonacog beta pegol after single dose is presented.
Time frame: 0-168 hours post-dosing at week 0
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Clearance (CL) | 0.764 Milliliters/hour/kilogram (mL/h/kg) | Standard Deviation 0.102 |
| Older Children (7-12 Years) | Clearance (CL) | 0.664 Milliliters/hour/kilogram (mL/h/kg) | Standard Deviation 0.147 |
Secondary
Development of Host Cell Protein (HCP) Antibodies
Participants were examined for the development of antibodies against HCP. Number of participants who developed antibodies against HCP is presented.
Time frame: From week 0 to EOT (approximately week 544)
Population: SAS included all participants exposed to nonacog beta pegol.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Younger Children (0-6 Years) | Development of Host Cell Protein (HCP) Antibodies | Yes | 1 Participants |
| Younger Children (0-6 Years) | Development of Host Cell Protein (HCP) Antibodies | No | 11 Participants |
| Older Children (7-12 Years) | Development of Host Cell Protein (HCP) Antibodies | Yes | 0 Participants |
| Older Children (7-12 Years) | Development of Host Cell Protein (HCP) Antibodies | No | 13 Participants |
Secondary
FIX Activity at 30 Minutes (C30min) (Single Dose)
FIX activity (international units per milliliter (IU/mL)) at 30 minutes after single dose is presented.
Time frame: 30 min post-dosing at week 0
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | FIX Activity at 30 Minutes (C30min) (Single Dose) | 0.544 IU/mL | Standard Deviation 0.04 |
| Older Children (7-12 Years) | FIX Activity at 30 Minutes (C30min) (Single Dose) | 0.600 IU/mL | Standard Deviation 0.074 |
Secondary
FIX Activity at 30 Minutes (C30min) (Steady State)
Mean FIX activity at 30 minutes post-dosing from week 4 to EOT approximately (week 544) (C30min) (steady state) is presented.
Time frame: 30 min post-dosing from week 4 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Younger Children (0-6 Years) | FIX Activity at 30 Minutes (C30min) (Steady State) | 0.174 IU/mL |
| Older Children (7-12 Years) | FIX Activity at 30 Minutes (C30min) (Steady State) | 0.197 IU/mL |
Secondary
FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes
Average dose of nonacog beta pegol for treatment of bleed from start to stop of bleed is presented from week 0 to EOT approximately (week 544) in international units per kilogram per bleed (IU/Kg/bleed). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes | 53.6 IU/kg/bleed | Standard Deviation 32.2 |
| Older Children (7-12 Years) | FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes | 50.1 IU/kg/bleed | Standard Deviation 19.4 |
| Adolescents(13-17 Years) | FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes | 84.3 IU/kg/bleed | Standard Deviation 110.2 |
| Adult (18-70 Years) | FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes | 59.9 IU/kg/bleed | Standard Deviation 32.7 |
Secondary
FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes
Consumption of nonacog beta pegol for treatment of bleeding episodes International units per kilogram per year (IU/Kg/year) per participant is presented from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes | 2209.3 IU/kg/year | Standard Deviation 79.3 |
| Older Children (7-12 Years) | FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes | 2324.9 IU/kg/year | Standard Deviation 83.5 |
| Adolescents(13-17 Years) | FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes | 2257.6 IU/kg/year | Standard Deviation 121.1 |
| Adult (18-70 Years) | FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes | 1959.5 IU/kg/year | Standard Deviation 533.4 |
Secondary
Haemophilia-quality of Life (HAEMO-QOL)
Haemophilia quality of life clustered into 11 multi-item scale which is used to assess haemophilia related quality of life such as children's physical health, feeling, family, friends, sport, treatment, dealing with haemophilia, view of a patient. Here, HAEMO-QOL was assessed for the children of age group 8-12 years. The scale range for each of 11 multi-item scale was 0-100 with high scores indicating low quality of life. Multi-item scores and total score were calculated using the following formula: 1/4(Sum of answered items / number of answered items - 1) x 100. HAEMO-QOL scores range from a 0 to 100 scale where high scores (nearing 100) indicate a low quality of life rating.
Time frame: Screening (week -6), week 52, EOT (approximately week 544)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed=participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: view | 20.1 Score on scale | Standard Deviation 22.5 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: view | 23.5 Score on scale | Standard Deviation 33.2 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : family | 25.0 Score on scale | Standard Deviation 16.5 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: family | 16.3 Score on scale | Standard Deviation 20.4 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: family | 17.5 Score on scale | Standard Deviation 24.7 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6): friends | 54.3 Score on scale | Standard Deviation 23 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: friends | 43.5 Score on scale | Standard Deviation 53 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : perceived support | 72.5 Score on scale | Standard Deviation 26.1 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: perceived support | 71.5 Score on scale | Standard Deviation 32 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: perceived support | 34.5 Score on scale | Standard Deviation 48.8 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : others | 14.3 Score on scale | Standard Deviation 12.5 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: others | 14.5 Score on scale | Standard Deviation 17.3 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: others | 8.5 Score on scale | Standard Deviation 12 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : sport | 20.8 Score on scale | Standard Deviation 19.4 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: sport | 28.0 Score on scale | Standard Deviation 26.9 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : dealing | 56.5 Score on scale | Standard Deviation 27.4 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: dealing | 49.6 Score on scale | Standard Deviation 22 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: dealing | 41.5 Score on scale | Standard Deviation 53 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : treatment | 34.7 Score on scale | Standard Deviation 16.7 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: treatment | 25.1 Score on scale | Standard Deviation 19.8 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: treatment | 11.0 Score on scale | Standard Deviation 0 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : total | 31.7 Score on scale | Standard Deviation 10.1 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: total | 28.0 Score on scale | Standard Deviation 12.5 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: total | 21.5 Score on scale | Standard Deviation 26.2 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: feeling | 12.8 Score on scale | Standard Deviation 22.9 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : view | 25.8 Score on scale | Standard Deviation 18.6 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: friends | 49.0 Score on scale | Standard Deviation 22.3 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: sport | 22.8 Score on scale | Standard Deviation 18.7 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : physical health | 19.8 Score on scale | Standard Deviation 19.1 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Week 52: physical health | 18.2 Score on scale | Standard Deviation 17 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: physical health | 7.0 Score on scale | Standard Deviation 9.9 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | Screening (week -6) : feeling | 15.5 Score on scale | Standard Deviation 19.3 |
| Younger Children (0-6 Years) | Haemophilia-quality of Life (HAEMO-QOL) | EOT approximately week 544: feeling | 12.5 Score on scale | Standard Deviation 17.7 |
Secondary
Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor)
Description of the haemostatic effect of nonacog beta pegol when used for treatment of bleeding episodes was measured and listed according to the four point scale for haemostatic response as below: 1. Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single infusion. 2. Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection. 3. Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one infusion within 8 hours. 4. Poor - no improvement, or worsening of symptoms within 8 hours after two injections. A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures.
Time frame: From week 0 to EOT (approximately week 544)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed=participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Younger Children (0-6 Years) | Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) | Success | 90.3 percentage of bleeding episodes |
| Younger Children (0-6 Years) | Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) | Failure | 9.7 percentage of bleeding episodes |
| Older Children (7-12 Years) | Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) | Success | 89.5 percentage of bleeding episodes |
| Older Children (7-12 Years) | Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) | Failure | 10.5 percentage of bleeding episodes |
Secondary
Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies
Health economic impact of N9-GP treatment through number of days bleedings caused missing school or studies. Number of participants who missed school or studies for 0,1 and 2 days are presented.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 0 days | 9 Participants |
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 1 day | 1 Participants |
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 2 days | 1 Participants |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 1 day | 0 Participants |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 0 days | 11 Participants |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies | 2 days | 2 Participants |
Secondary
Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation
Health economic impact of N9-GP treatment is presented through number of intensive care hospitalization days.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analyzed = number of participants with available data. Number analysed = participants analysed for specific category for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation | 0.0 Days | Standard Deviation 0 |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation | 0.0 Days | Standard Deviation 0 |
Secondary
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work
Health economic impact of N9-GP treatment through number of days bleeding caused parents to miss work is presented from week 0 to EOT approximately (week 544).
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work | 0.3 Days | Standard Deviation 0.6 |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work | 0.5 Days | Standard Deviation 0.9 |
Secondary
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids
Health economic impact of N9-GP treatment through number of days the patient used mobility aids (wheelchair and/or crutches) is presented.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids | 0.4 Days | Standard Deviation 0.7 |
| Older Children (7-12 Years) | Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids | 1.0 Days | Standard Deviation 3.3 |
Secondary
Hemophilia Treatment Satisfaction (HEMO-SAT)
Haemophilia treatment satisfaction change from baseline (screening week -6) to week 176 (visit 17) is presented. The treatment satisfaction of a bleed with N8-GP was assessed using HEMO-SAT assessment tool which contains a questionnaire with 6 domains (Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction). The scale range for each 6 domains was (0-100) with lower score indicating higher treatment satisfaction. HEMO-SAT was assessed for the children of age group 4-7 years and 8-12 years. Domain score and total score were calculated using following formula - 1/4 (sum of answered items / Number of answered item - 1) x 100. HEMO-SAT scores range from 0-100, where low scores reflecting greater treatment satisfaction.
Time frame: Screening (Week -6), week 176 (visit 17)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Ease and convenience | -6.5 Score on scale | Standard Deviation 19.4 |
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Efficacy | -3.8 Score on scale | Standard Deviation 21.3 |
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Burden | -15.8 Score on scale | Standard Deviation 16 |
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Specialist/nurses | -1.8 Score on scale | Standard Deviation 2.1 |
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Centre/hospital | 5.0 Score on scale | Standard Deviation 13.5 |
| Younger Children (0-6 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | General satisfaction | -6.3 Score on scale | Standard Deviation 12.5 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Centre/hospital | -2.3 Score on scale | Standard Deviation 6.1 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Ease and convenience | -13.4 Score on scale | Standard Deviation 16.2 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Specialist/nurses | -0.6 Score on scale | Standard Deviation 2.1 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Efficacy | -14.5 Score on scale | Standard Deviation 23.8 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | General satisfaction | -3.5 Score on scale | Standard Deviation 8.1 |
| Older Children (7-12 Years) | Hemophilia Treatment Satisfaction (HEMO-SAT) | Burden | -8.5 Score on scale | Standard Deviation 13 |
Secondary
Incremental Recovery at 30 Minutes (IR30min)
The incremental recovery was calculated by dividing the baseline-subtracted factor IX activity Units per milliliter (U/mL) measured in plasma 30 min after dosing by the dose injected at time 0 expressed as units per kilogram (U/kg) body weight.
Time frame: Week 0 (30 minutes after first exposure)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = Participants who were evaluated for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Incremental Recovery at 30 Minutes (IR30min) | 0.015 (U/mL)/(U/kg) | Geometric Coefficient of Variation 7.31 |
| Older Children (7-12 Years) | Incremental Recovery at 30 Minutes (IR30min) | 0.016 (U/mL)/(U/kg) | Geometric Coefficient of Variation 16.18 |
Secondary
Mean Residence Time (MRT)
Mean residence time (MRT) of nonacog beta pegol after single dose is presented.
Time frame: 0-168 hours post-dosing at week 0
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Mean Residence Time (MRT) | 96.332 Hour (h) | Standard Deviation 12.995 |
| Older Children (7-12 Years) | Mean Residence Time (MRT) | 108.16 Hour (h) | Standard Deviation 29.937 |
Secondary
Medical Events of Special Interest (MESI)
The following events were defined as MESIs: -Medication errors concerning trial products, -Administration of wrong drug, * Wrong route of administration, * Administration of a high dose with the intention to cause harm, e.g. suicide attempt, * Administration of an accidental overdose: more than 20 % from the intended dose, * Inhibitor formation against factor IX (FIX), * Thromboembolic events, * Anaphylactic reaction. * Allergic reaction including, but not limited to, any acute immunoglobulin E (IgE) mediated reaction or delayed type hypersensitivity. Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: Week 0 to EOT (approximately week 544)
Population: SAS included all participants exposed to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Younger Children (0-6 Years) | Medical Events of Special Interest (MESI) | 1 Events |
| Older Children (7-12 Years) | Medical Events of Special Interest (MESI) | 3 Events |
| Adolescents(13-17 Years) | Medical Events of Special Interest (MESI) | 5 Events |
| Adult (18-70 Years) | Medical Events of Special Interest (MESI) | 1 Events |
Secondary
Number of Adverse Events
An adverse event (AE) was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Here, data is presented for all adverse events (serious adverse events and other adverse events) from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: Week 0 to EOT (approximately week 544)
Population: SAS included all participants exposed to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Younger Children (0-6 Years) | Number of Adverse Events | 252 Events |
| Older Children (7-12 Years) | Number of Adverse Events | 342 Events |
| Adolescents(13-17 Years) | Number of Adverse Events | 81 Events |
| Adult (18-70 Years) | Number of Adverse Events | 10 Events |
Secondary
Number of Bleeding Episodes During Prophylaxis
The number of bleeding episodes per participant during routine prophylaxis was assessed using the individual annualised bleeding rates (bleeding episodes per participant per year).
Time frame: From week 0 to EOT (approximately week 544)
Population: Full analysis set (FAS) included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Younger Children (0-6 Years) | Number of Bleeding Episodes During Prophylaxis | 0.33 bleeds/participant/year |
| Older Children (7-12 Years) | Number of Bleeding Episodes During Prophylaxis | 0.78 bleeds/participant/year |
Secondary
Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes
Number of doses of FIX consumed for the treatment of bleeding episodes is presented from week 0 to EOT approximately (week 544). Here, data of number of doses of FIX for the treatment of bleeding episodes is reported among all the participants in an arm. Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Younger Children (0-6 Years) | Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes | 1768 Doses of FIX |
| Older Children (7-12 Years) | Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes | 4201 Doses of FIX |
| Adolescents(13-17 Years) | Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes | 2740 Doses of FIX |
| Adult (18-70 Years) | Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes | 747 Doses of FIX |
Secondary
Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation
Number of participants with health economic impact of N9-GP treatment through characterisation of general hospitalisation is presented. Number of participants hospitalised for 0 & 1 day is presented.
Time frame: From week 0 to EOT (approximately week 544)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Younger Children (0-6 Years) | Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation | 0 Days | 3 Participants |
| Younger Children (0-6 Years) | Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation | 1 Day | 1 Participants |
| Older Children (7-12 Years) | Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation | 1 Day | 0 Participants |
| Older Children (7-12 Years) | Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation | 0 Days | 5 Participants |
Secondary
Number of Serious Adverse Events (SAEs)
A SAE was an experience that at any dose resulted in any of the following: death, a life-threatening experience a), In-patient hospitalisation or prolongation of existing hospitalisation b) a persistent or significant disability/incapacity c) a congenital anomaly/birth defect, Important medical events d) that did not result in death, were life-threatening a) or required hospitalization. Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: Week 0 to EOT (approximately week 544)
Population: SAS included all participants exposed to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Younger Children (0-6 Years) | Number of Serious Adverse Events (SAEs) | 3 Events |
| Older Children (7-12 Years) | Number of Serious Adverse Events (SAEs) | 5 Events |
| Adolescents(13-17 Years) | Number of Serious Adverse Events (SAEs) | 1 Events |
| Adult (18-70 Years) | Number of Serious Adverse Events (SAEs) | 0 Events |
Secondary
Terminal Half-life (t1/2)
Terminal half life is presented at week 0, 30 minutes until one week after first exposure.
Time frame: Week 0 (30 minutes until one week after first exposure)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Terminal Half-life (t1/2) | 69.576 hours | Geometric Coefficient of Variation 15.79 |
| Older Children (7-12 Years) | Terminal Half-life (t1/2) | 76.323 hours | Geometric Coefficient of Variation 25.48 |
Secondary
TNO-AZL Preschool Quality of Life (TAPQOL)
The Dutch institute of Prevention and Health and the Leiden University Hospital (TNO-AZL) preschool quality of life clustered into 12 multi-item scales is used to assess the health-related quality of life, such as children's motor, communication, emotions, and body structure. Suitable for children from 6 months to 6 years old (TAPQOL). Parents fill in according to the child's condition. Higher score (range 0-100) represents better outcome. The scale range for each of 12 multi-item scales was (0-100) with high score representing better outcome. In this study, the TAPQOL was assessed for children of age 0-3 years.
Time frame: Screening (Week -6), week 52, week 176 approximately (visit 17)
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = participants who experienced bleeding episodes. Number analysed = participants analysed for specific category for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Sleeping problems | 80.4 Score on scale | Standard Deviation 15.3 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Lung problems | 93.2 Score on scale | Standard Deviation 13.2 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Anxiety | 75.0 Score on scale | Standard Deviation 22.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Liveliness | 100.0 Score on scale | Standard Deviation 0 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Sleeping problems | 76.0 Score on scale | Standard Deviation 15.5 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Appetite | 91.7 Score on scale | Standard Deviation 11.8 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Appetite | 90.3 Score on scale | Standard Deviation 15.2 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Lung problems | 100.0 Score on scale | Standard Deviation 0 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Stomach problems | 93.0 Score on scale | Standard Deviation 12.1 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Stomach problems | 90.3 Score on scale | Standard Deviation 15.2 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Skin problems | 88.1 Score on scale | Standard Deviation 17.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Skin problems | 90.3 Score on scale | Standard Deviation 16.3 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Motor functioning | 98.0 Score on scale | Standard Deviation 4.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Motor functioning | 98.0 Score on scale | Standard Deviation 4.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6): Social functioning | 97.2 Score on scale | Standard Deviation 6.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Social functioning | 97.2 Score on scale | Standard Deviation 6.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Problem behavior | 58.1 Score on scale | Standard Deviation 40.8 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Problem behavior | 53.7 Score on scale | Standard Deviation 29.6 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Communication | 92.8 Score on scale | Standard Deviation 14.8 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Communication | 87.5 Score on scale | Standard Deviation 14.2 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Anxiety | 76.1 Score on scale | Standard Deviation 16.1 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Positive mood | 92.9 Score on scale | Standard Deviation 18.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Week 52: Positive mood | 100.0 Score on scale | Standard Deviation 0 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Screening (week -6) : Liveliness | 97.6 Score on scale | Standard Deviation 6.4 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: sleeping problem | 89.7 Score on scale | Standard Deviation 15 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Appetite | 94.5 Score on scale | Standard Deviation 10.1 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Lung problems | 97.2 Score on scale | Standard Deviation 6.9 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Stomach problems | 83.2 Score on scale | Standard Deviation 10.4 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Skin problems | 84.7 Score on scale | Standard Deviation 20 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Motor functioning | 99.0 Score on scale | Standard Deviation 2.4 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Social functioning | 86.2 Score on scale | Standard Deviation 22.1 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Problem behavior | 58.3 Score on scale | Standard Deviation 19.3 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Communication | 95.8 Score on scale | Standard Deviation 10.2 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Anxiety | 80.2 Score on scale | Standard Deviation 18.1 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Positive mood | 100.0 Score on scale | Standard Deviation 0 |
| Younger Children (0-6 Years) | TNO-AZL Preschool Quality of Life (TAPQOL) | Approximately week 176: Liveliness | 94.3 Score on scale | Standard Deviation 8.8 |
Secondary
Trough Level (Single-dose )
The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Geometric mean of the lowest activity of factor IX recorded at week 0 (immediately before next dose was given).
Time frame: Week 0 (one week after first exposure)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol. Here, overall number of participants analysed = Participants who were evaluated for this parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Trough Level (Single-dose ) | 0.084 U/mL | Geometric Coefficient of Variation 16.28 |
| Older Children (7-12 Years) | Trough Level (Single-dose ) | 0.109 U/mL | Geometric Coefficient of Variation 18.89 |
Secondary
Trough Level (Steady State)
The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. The estimated mean of the lowest activity recorded immediately before next dose was given from week 4 to EOT approximately (week 544). Data is reported for specific age groups in which participants were a part of at any time from week 4 to EOT, not at specific time points assessed from week 4 to EOT. The analysis is based on a mixed model on the log-transformed plasma concentrations with participant as a random effect and the mean trough level is presented back-transformed to the natural scale. Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Time frame: From week 4 to EOT (approximately week 544)
Population: FAS included all participants with efficacy data after exposure to nonacog beta pegol.~Age groups are based on actual age, therefore some participants are represented in multiple columns.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Younger Children (0-6 Years) | Trough Level (Steady State) | 0.146 U/mL |
| Older Children (7-12 Years) | Trough Level (Steady State) | 0.193 U/mL |
| Adolescents(13-17 Years) | Trough Level (Steady State) | 0.220 U/mL |
| Adult (18-70 Years) | Trough Level (Steady State) | 0.316 U/mL |
Secondary
Volume of Distribution at Steady State (Vss)
Volume of distribution at steady state (Vss) of nonacog beta pegol is presented.
Time frame: 0-168 hours post-dosing at week 0
Population: The FAS included all participants with efficacy data after exposure to nonacog beta pegol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Younger Children (0-6 Years) | Volume of Distribution at Steady State (Vss) | 73.046 Milliliters per kilogram (mL/kg) | Standard Deviation 10.843 |
| Older Children (7-12 Years) | Volume of Distribution at Steady State (Vss) | 69.752 Milliliters per kilogram (mL/kg) | Standard Deviation 15.253 |