Evaluation of Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Subjects With Haemophilia A
- Conditions
- Congenital Bleeding DisorderHaemophilia A
- Interventions
- Registration Number
- NCT01480180
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial is conducted globally. The aim of the trial is to evaluate the safety and efficacy, including pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP) in subjects with Haemophilia A.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 186
- Male patients with severe congenital haemophilia A (FVIII activity below 1%, according to medical records) - Documented history of at least 150 EDs (exposure days) to other FVIII products - At least 12 years and body weight at least 35 kg (except for Croatia, France, Russia, Israel and the Netherlands where the lower age limit will be 18 years)
- Previous participation in this trial defined as withdrawal after administration N8-GP - Any history of FVIII inhibitors - FVIII inhibitors above or equal to 0.6 BU/mL at screening - HIV (human immunodeficiency virus) positive, defined by medical records with CD4+ (T-lymphocyte subtype) count below or equal to 200/mcL or a viral load of more than 400000 copies/mL. If the data is not available in medical records within last 6 months, CD4+ will be measured at the screening visit - Congenital or acquired coagulation disorders other than haemophilia A - Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records - Platelet count below 50,000 platelets/mcL (laboratory value at the screening visit) - ALAT (alanine aminotransferase) above 3 times the upper limit of normal reference ranges at central laboratory - Creatinine level equal to or greater than 1.5 times above upper normal limit (according to central laboratory reference ranges) - Ongoing immune modulating or chemotherapeutic medication
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prophylaxis turoctocog alfa pegol - On-demand turoctocog alfa pegol -
- Primary Outcome Measures
Name Time Method Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months After approximately 25 months ABR is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.
The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months After approximately 19 months All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months After approximately 19 months Annualised bleeding rate (ABR) is the number of bleeding episodes per year. This was assessed only for the prophylaxis treatment with N8-GP.
The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months After approximately 25 months All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months At approximately 80 months All participants with neutralizing antibodies were included in the numerator and any participant with a minimum 50 exposure days plus any participant with inhibitory inhibitors was included in the denominator. A positive inhibitor test was defined as ≥0.6 bethesda unit (BU). Estimates are based on exact calculations for a binomial distribution. For the calculation of the 'inhibitor rate' the nominator included all participants with neutralising antibodies while the denominator included all participants with a minimum of 50 exposures plus any participant with less than 50 exposures but with neutralising inhibitors.
Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months After approximately 80 months Annualised bleeding rate (ABR) is the number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.
- Secondary Outcome Measures
Name Time Method Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 80 Months After approximately 80 months Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months After approximately 19 months The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months After approximately 25 months The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months After approximately 25 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months After approximately 19 months Recovery and trough levels of FVIII:C was reported for all participants at Visit 3 (Week 4) and end of main phase (approx. 19 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.
Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 25 Months After approximately 25 months Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 19 Months After approximately 19 months Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.
Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months After approximately 25 months The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months After approximately 25 months Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.
Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.
Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HAEM-A-QOL (for adults (\>=17 years)) assessment included questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.
Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HEMO-SAT (Hematology-satisfaction) assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. A decrease in the score would mean improvement.
Number of Days at the Hospital During the Trial After approx 19, 25 and 80 months The mean number of days that participants spent at the hospital during the study were reported.
Number of Admissions to the Emergency Room (ER) During the Trial After approx 19, 25 and 80 months The number of admissions to the ER that took place in the study were reported for each group.
Number of Days Missing School or Work Approx 19, 25 and 80 months The mean number of days that participants missed to go to school or work were reported.
Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months After approximately 80 months The mean number of infusions of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months After approximately 19 months The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months After approximately 80 months The mean consumption of N8-GP (U/kg) used for treatment of a bleed from start to stop of a bleed was reported.
Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months After approximately 19 months Number of infusions are presented as average dose used during propphylaxis and on-demand treatment.
Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months After approximately 19 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months After approximately 19 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months After approximately 80 months Number of infusions are presented as average dose used during prophylaxis and on-demand treatment.
Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months After approximately 25 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months After approximately 80 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per month per participant) was reported.
Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months After approximately 80 months The mean consumption of N8-GP used for treatment of a bleed from start to stop of a bleed (per year per participant) was reported.
Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 80 Months After approximately 80 months Since patients were allowed to change prophylaxis regimen at any time during the extension phase part 2, and since the visit intervals were different for the 2 prophylaxis treatment regimens (Q4D and Q7D), FVIII activity data are reported only as incremental recovery at this timepoint.
Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (approx Month 19) and change from Month 19 at end of Extension 1 (approx Month 25) of the study. The HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.
Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months After approximately 25 months Recovery and trough levels of FVIII:C was reported for all participants at the end of extension phase 1 study (approx. 25 months). The data was reported for all participants who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator.
Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by patients). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. A decrease in the score would mean improvement.
Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months After approx 19 and 25 months The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0). The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction (reported by parents). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. A decrease in the score would mean improvement.
Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point. The EQ5D-VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.
Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life utility index comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.
Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It is possible that a patient answers more than one questionnaire in a single time interval. Overall units analysed = Max no. of questionnaires answered by participants for this endpoint. Overall no. of participants analysed = max no. of participants analysed at each time point. This utility index has 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 3 levels where 1 indicates better health state (no problems) and 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; a positive change indicates an improvement.
Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. The HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.
Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The HAEM-A-QOL (for adults (\>=17 years)) assessment included questions on questions on physical health, feeling, view of yourself, sports and leisure, work and school, dealing with haemophilia, treatment, future, family planning, and partnership and sexuality. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia.
Number of Days Using Mobility Aid Approx 19, 25 and 80 months The mean number of days that participants used any aids for mobility during the study were reported.
Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are change from visit 1 (Month 0) upto end of Extension phase 2 (Month 80) of the study. The questionnaire was completed by parents of the patients in the 13-16 years old age bracket. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. The HAEMO-QOL assessment included questions on physical health, feeling, view of yourself, family, friends, perceived support, other persons, sports and school, dealing with haemophilia, treatment, future, and relationships. Scores range for each question was 0-100, with a lower score indicating better quality of life related to haemophilia. Overall number of units analysed = Maximum no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = maximum number of participants contributed to the analysis for each time point.
Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs Reported results are from Visit 1 (Month 0), and change from visit 1 upto end of Extension phase 2 (Month 80) of the study. Time intervals are assigned based on time after first dose. It was possible that a participant could answer more than one questionnaire in a single time interval. Overall number of units analysed = Max. no of questionnaires answered by participants for this endpoint. Overall number of participants analysed = max. number of participants contributed to the analysis for each time point. The HEMO-SAT assessment included questions on treatment aspects including Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction. Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. A decrease in the score would mean improvement.
Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months After approx 19 and 25 months Reported results are change from baseline (Month 0) measured at end of main phase (Month 19) and change from Month 19 to end of Extension 1 (Month 25) of the study. The European quality of life visual analogue scale (EQ5D-VAS) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. EQ-5D-VAS: range 0 to 100. A higher score indicates better self reported health status. A positive change indicates an improvement.
Number of Hospital Admissions During the Trial After approx 19, 25 and 80 months The number of hospital admissions that took place in the study were reported.
Number of Participants Using Pain Medication After approx 25 and 80 months The number of participants using pain medication during the main plus extension phase 1 of the study (approximately 25 months) and during extension phase 2(approximately 80 months) were reported.
Number of Bleeds Using Pain Medication After approx 19 months The mean number of bleeds using pain medication in the main phase of the study (approximately 19 months) were reported.
Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months After approx 19 months All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months After approx. 25 months All presented adverse events (AEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months After approximately 19 months All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months After approximately 80 months All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Change in Blood Pressure: After Approximately 25 Months After approximately 19 and 25 months The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
Change in Blood Pressure: After Approximately 80 Months After approximately 80 months Change in the blood pressure was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
Change in Pulse: After Approximately 25 Months After approximately 25 months The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
Change in Pulse: After Approximately 80 Months After approximately 80 months Change in pulse was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
Change in Body Temperature: After Approximately 80 Months After approximately 80 months Change in body temperature was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
Change in Respiratory Rate: After Approximately 25 Months After approximately 25 months The mean change in the respiratory rate (breaths/min) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months After approximately 80 months The number of adverse events observed during the study after approximately 80 months was reported.
Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months After approximately 25 months All presented serious adverse events (SAEs) are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.
Change in Blood Pressure: After Approximately 19 Months After approximately 19 months The mean change in the systolic and diastolic blood pressure values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
Change in Pulse: After Approximately 19 Months After approximately 19 months The mean change in the pulse values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
Change in Body Temperature: After Approximately 19 Months After approximately 19 months The mean change in the body temperature values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
Change in Body Temperature: After Approximately 25 Months After approximately 25 months The mean change in the body temperature (C) values of participants was reported. The summary of change was based on individual changes observed at visit 17 (approximately month 25) from visit 13 (approximately month 19).
Change in Respiratory Rate: After Approximately 19 Months After approximately 19 months The mean change in the respiratory rate values of participants was reported. The summary of change was based on individual changes observed at visit 13 (approximately 19 months) from visit 2a pre-dose (Month 0).
Change in Respiratory Rate: After Approximately 80 Months After approximately 80 months Change in respiratory rate was not calculated in the extension phase 2 of the study since participants were allowed to change from Q4D to Q7D and vice versa.
FVIII Activity 30 Min Post -Injection (C30min) Week 0, week 28 FVIII plasma activity was measured after 30 mins of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator
Incremental Recovery (Single Dose and Steady State) Week 0, week 28 Incremental recovery was defined as the dose-normalised activity recorded 30 min after end of injection. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Trough Level (Single Dose and Steady State) Week 0, week 28 Trough level was defined as the plasma FVIII activity recorded immediately before next dose is given. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Area Under the Curve (AUC0-inf) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. It is the measure of total plasma exposure. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Area Under the Curve (AUC0-t) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 Area under the plasma activity versus time profile from time zero to the last measurable activity (AUC0-t) was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Mean Residence Time (MRT) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 MRT = AUMC/AUC(0-inf), where AUMC is the area under the first moment curve, i.e. the area under the curve t∙C(t), calculated with the same method as AUC(0-inf) (linear trapezoidal method + extrapolated area). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Volume of Distribution at Steady State (Vss) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 Apparent volume of distribution at steady state is a product of the mean residence time and clearance and was calculated using the formula - Vss = CL x MRT. This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Terminal Half Life (t1/2) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 t½ = 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. This was measured at Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Clearance (CL) Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28 Total plasma clearance (CL) of drug after intravenous administration was reported. Clearance was calculated using the formula CL= Dose / AUC(0-inf). This was measured at two time points Visit 2a (Week 0) and visit 7 (Week 28) during the Main Phase of the study. Chromogenic assay was performed with normal human plasma (NHP) as a calibrator.
Trial Locations
- Locations (1)
Novo Nordisk Investigational Site
🇬🇧Sheffield, United Kingdom