A Multi-national Trial Evaluating Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Patients With Haemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Prophylaxis
干预措施: turoctocog alfa pegol (Drug)
On-demand
干预措施: turoctocog alfa pegol (Drug)
结局指标
主要结局
Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: After approximately 80 months
Annualised bleeding rate (ABR) is the number of bleeding episodes per year reported during the prophylactic treatment with N8-GP.
次要结局
- 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)
- Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months(After approximately 25 months)
- Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months(After approximately 19 months)
- Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months(After approximately 25 months)
- 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)
- 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 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)
- Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months(After approximately 25 months)
- Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months(After approximately 25 months)
- 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)
- 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)
- Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months(After approx 19 and 25 months)
- Number of Days at the Hospital During the Trial(After approx 19, 25 and 80 months)
- Number of Admissions to the Emergency Room (ER) During the Trial(After approx 19, 25 and 80 months)
- Number of Days Missing School or Work(Approx 19, 25 and 80 months)
- Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months(After approximately 80 months)
- Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months(After approximately 19 months)
- Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months(After approximately 80 months)
- Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months(After approximately 19 months)
- Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months(After approximately 19 months)
- Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months(After approximately 19 months)
- Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months(After approximately 80 months)
- Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months(After approximately 25 months)
- Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months(After approximately 80 months)
- Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months(After approximately 80 months)
- 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)
- 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)
- 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)
- 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)
- Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months(After approx 19 and 25 months)
- 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)
- Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months(After approx 19 and 25 months)
- 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)
- 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)
- Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months(After approx 19 and 25 months)
- Number of Days Using Mobility Aid(Approx 19, 25 and 80 months)
- 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)
- 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)
- Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months(After approx 19 and 25 months)
- Number of Hospital Admissions During the Trial(After approx 19, 25 and 80 months)
- Number of Participants Using Pain Medication(After approx 25 and 80 months)
- Number of Bleeds Using Pain Medication(After approx 19 months)
- Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months(After approx 19 months)
- Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months(After approx. 25 months)
- Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months(After approximately 19 months)
- Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months(After approximately 80 months)
- Change in Blood Pressure: After Approximately 25 Months(After approximately 19 and 25 months)
- Change in Blood Pressure: After Approximately 80 Months(After approximately 80 months)
- Change in Pulse: After Approximately 25 Months(After approximately 25 months)
- Change in Pulse: After Approximately 80 Months(After approximately 80 months)
- Change in Body Temperature: After Approximately 80 Months(After approximately 80 months)
- Change in Respiratory Rate: After Approximately 25 Months(After approximately 25 months)
- Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months(After approximately 80 months)
- Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months(After approximately 25 months)
- Change in Blood Pressure: After Approximately 19 Months(After approximately 19 months)
- Change in Pulse: After Approximately 19 Months(After approximately 19 months)
- Change in Body Temperature: After Approximately 19 Months(After approximately 19 months)
- Change in Body Temperature: After Approximately 25 Months(After approximately 25 months)
- Change in Respiratory Rate: After Approximately 19 Months(After approximately 19 months)
- Change in Respiratory Rate: After Approximately 80 Months(After approximately 80 months)
- FVIII Activity 30 Min Post -Injection (C30min)(Week 0, week 28)
- Incremental Recovery (Single Dose and Steady State)(Week 0, week 28)
- Trough Level (Single Dose and Steady State)(Week 0, week 28)
- 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 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)
- 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)
- 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)
- 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)
- Clearance (CL)(Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28)