Efficacy and Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A

Study Overview
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Brief Summary
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This trial is conducted in China. The aim of this trial is to evaluate the clinical efficacy of turoctocog alfa in treatment of bleeding episodes in Chinese patients with severe haemophilia A (FVIII≤1%).

Official Title
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Efficacy and Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A

Conditions
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Congenital Bleeding Disorder, Haemophilia A

Intervention / Treatment
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* Drug: turoctocog alfa
* Drug: turoctocog alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients Age from 0 years With the diagnosis of severe congenital haemophilia A (FVIII≤1%) History of exposure days (ED) to any FVIII products fulfilling the criteria of previously treated patients: Patients of 12 years or above: 100 exposures days (ED) or more Patients below 12 years: 50 exposure days (ED) or more Exclusion Criteria: Inhibitors to factor VIII (≥0.6 BU) at screening as assessed by central laboratory Known history of FVIII inhibitors
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic treatment<br> | Drug: turoctocog alfa<br>* The preventative treatment is administered intravenously (i.v.) at specific intervals either every second day or three times a week. Bleeding treatment will be administered if a bleed should occur.<br>|
| Experimental: On-demand treatment<br> | Drug: turoctocog alfa<br>* Treatment is administered intravenously (i.v.) during bleeds and occasionally as a preventative treatment (e.g. before physical activity)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months | The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none. | Month 0-6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months | The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes in both prophylaxis and on-demand regimen was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response, excellent, good, moderate and none. | Month 0-24 | 
| Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months | This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-6. | Month 0-6 | 
| Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months | This endpoint presented 'percentage of participants with inhibitory antibodies against FVIII (≥0.6 BU)' in both prophylaxis and on-demand regimen, evaluated during month 0-24. | Month 0-24 | 
| Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months | Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-6. The annualised bleeding rate was analysed by a negative binomial model. | Month 0-6 | 
| Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months | Number of bleeds (total bleeds assessed as annual bleeding rate) per participant in the prophylaxis regimen was evaluated during month 0-24. The annualised bleeding rate was analysed by a negative binomial model. | Month 0-24 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) | Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) | Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24. | Month 0-24 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) | Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) | Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-24. | Month 0-24 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) | Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) | Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24. | Month 0-24 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) | Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) | Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-24. | Month 0-24 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-24. | Month 0-24 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) | Preventive dose of turoctocog alfa (IU/kg body weight per year) per participant in the prophylaxis regimen was evaluated during month 0-6. | Month 0-6 | 
| Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) | Preventive dose of turoctocog alfa (IU/kg body weight (BW) per year) per participant in the prophylaxis regimen was evaluated during month 0-24. | Month 0-24 | 
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) | Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6. | Month 0-6 | 
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) | Total consumption of turoctocog alfa (IU/kg body weight per month) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24. | Month 0-24 | 
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) | Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-6. | Month 0-6 | 
| Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) | Total consumption of turoctocog alfa (IU/kg body weight per year) per participant in both prophylaxis and on-demand regimen was evaluated during month 0-24. | Month 0-24 | 
| Frequency of Adverse Events (6 Months) | Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-6 | 
| Frequency of Adverse Events (24 Months) | Frequency of adverse events (AEs) are presented as rate of events, which was calculated as the number of AEs per patient years. All presented AEs are treatment emergent (TEAEs), which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-24 | 
| Frequency of Serious Adverse Events (6 Months) | Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-6 | 
| Frequency of Serious Adverse Events (24 Months) | Frequency of serious adverse events (SAEs) are presented as rate of events, which was calculated as the number of SAEs per patient years. All presented SAEs are treatment emergent, which were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-24 | 
| Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months | The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-6. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site. | Month 0-6 | 
| Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months | The haemostatic effect of turoctocog alfa when used for surgery was evaluated during month 0-24. The effect was assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) and assessed by the investigator/surgeon on the day of surgery (day 1) and on the last day in the post-operative period the participant was at the trial/surgery site. Haemostatic response of 'not applicable' indicated that turoctocog alfa was not used. | Month 0-24 | 
| Loss of Blood (Surgery): 6 Months | Loss of blood was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. | Month 0-6 | 
| Loss of Blood (Surgery): 24 Months | Loss of blood was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. | Month 0-24 | 
| Requirements for Transfusion (Surgery): 6 Months | Surgeries required transfusion was evaluated during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. | Month 0-6 | 
| Requirements for Transfusion (Surgery): 24 Months | Surgeries required transfusion was evaluated during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. | Month 0-24 | 
| Adverse Events (Surgery): 6 Months | TEAEs during surgery were recorded during month 0-6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-6 | 
| Adverse Events (Surgery): 24 Months | TEAEs during surgery were recorded during month 0-24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant was at the trial/surgery site whatever comes first. TEAEs were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-24 | 
| Serious Adverse Events (Surgery): 6 Months | Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 6: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-6 | 
| Serious Adverse Events (Surgery): 24 Months | Treatment emergent serious adverse events occurred during surgery were recorded from month 0 to month 24: on the day of surgery (day 1) and during the post-operative period days 2-7 or until the last day the participant is at the trial/surgery site whatever comes first. Treatment emergent events were defined as the events reported after trial product administration until the end of the post-treatment follow-up period. | Month 0-24 | 
| Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 | Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)) and HAEM-A-QOL (for adults (>=17 years)). 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. HAEM-A-QOL 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. Observed mean of the means of all the questions for HAEMO-QOL and HAEM-A-QOL, respectively are presented. | Month 0, Month 6 | 
| Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 | Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific HRQOL. HRQOL was collected through use of the patient reported outcome (PRO) instruments, HAEM-A-QOL (for adults (>=17 years)) and HAEMO-QOL (for children (8-12 years)/adolescents (13-16 years)). HAEM-A-QOL 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. 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. Observed mean of the means of all the questions for HAEM-A-QOL and HAEMO-QOL, respectively are presented. | Month 0, Month 24 | 
| Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 | Reported results are baseline (month 0) and change from baseline (at month 6) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, 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. Observed mean of the means of all the questions for HAEMO-QOL are presented. | Month 0, Month 6 | 
| Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 | Reported results are baseline (month 0) and change from baseline (at month 24) of end of disease and age specific health related quality of life (HRQOL). HRQOL was collected through use of the PRO instrument, HAEMO-QOL (for parents of the children (4-7 years and 8-12 years)/adolescents (13-16 years)). HAEMO-QOL assessment included questions on physical health, feeling, view of himself, family, friends, perceived support, other persons, nursery School or Kindergarten, 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. Observed mean of the means of all the questions for HAEMO-QOL are presented. | Month 0, Month 24 | 
| Incremental Recovery of FVIII | Blood samples for the evaluation of incremental recovery of FVIII were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The incremental recovery was calculated as (FVIII: coagulant (C) activity measured in plasma 30 minutes after dosing - FVIII:C activity measured in plasma immediately before dosing)/(dose injected at time 0 minute), where the dose was expressed as IU FVIII product per kg body weight. The results are based on the chromogenic assay. | Days 1-2 | 
| Area Under the Curve (AUC0-inf) | Blood samples for the evaluation of AUC0-inf were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. AUC0-inf was defined as the area under the concentration versus time from time curve zero to infinity. The results are based on the chromogenic assay. | Days 1-2 | 
| Half-life (t½) | Blood samples for the evaluation of t½ were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. | Days 1-2 | 
| Clearance (CL) | Blood samples for the evaluation of CL were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. | Days 1-2 | 
| Highest Measured FVIII Activity in the Profile (Cmax) | Blood samples for the evaluation of Cmax were taken during a period of 48 hours post-dosing for participants 12 years and older and 24 hours post-dosing for participants below the age of 12 years. The results are based on the chromogenic assay. | Days 1-2 |