Efficacy and Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A (guardian TM 7)

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%).

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia A
• Intervention / Treatment: Drug: turoctocog alfa; Drug: turoctocog alfa

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100045
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chonqqing, Chongqing, China, 400014
      • Novo Nordisk Investigational Site
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Novo Nordisk Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Novo Nordisk Investigational Site
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • Novo Nordisk Investigational Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novo Nordisk Investigational Site
  • Qinghai
    • Xining, Qinghai, China, 810007
      • Novo Nordisk Investigational Site
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjing, Tianjin, China, 300020
      • Novo Nordisk Investigational Site
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Novo Nordisk Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic treatment	Drug: turoctocog alfa; 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.; Drug: turoctocog alfa; Treatment is administered intravenously (i.v.) during bleeds and occasionally as a preventative treatment (e.g. before physical activity)
Experimental: On-demand treatment	Drug: turoctocog alfa; 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.; Drug: turoctocog alfa; Treatment is administered intravenously (i.v.) during bleeds and occasionally as a preventative treatment (e.g. before physical activity)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2016
• Primary Completion (Actual): March 16, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 18, 2016
• First Posted (Estimate): October 19, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Hemorrhage; Coagulants; Factor VIII
• Other Study ID Numbers: NN7008-4028; U1111-1150-0765 (Other Identifier: WHO); CTR20160811 (Other Identifier: CFDA); 2013-004791-35 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No