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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 (guardian TM 7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02938585
Recruitment Status : Completed
First Posted : October 19, 2016
Results First Posted : August 26, 2019
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
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%).

Condition or disease Intervention/treatment Phase
Congenital Bleeding Disorder Haemophilia A Drug: turoctocog alfa Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A
Actual Study Start Date : December 12, 2016
Actual Primary Completion Date : March 16, 2018
Actual Study Completion Date : December 12, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Hemophilia

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.

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




Primary Outcome Measures :
  1. Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 6 Months [ Time Frame: Month 0-6 ]
    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.


Secondary Outcome Measures :
  1. Haemostatic Effect of Turoctocog Alfa (Treatment of Bleeds): 24 Months [ Time Frame: Month 0-24 ]
    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.

  2. Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 6 Months [ Time Frame: Month 0-6 ]
    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.

  3. Incidence Rate of Inhibitory Antibodies Against FVIII (≥0.6 BU): 24 Months [ Time Frame: Month 0-24 ]
    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.

  4. Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 6 Months [ Time Frame: Month 0-6 ]
    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.

  5. Number of Bleeds (Total Bleeds Assessed as Annual Bleeding Rate) Per Participant: 24 Months [ Time Frame: Month 0-24 ]
    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.

  6. Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (6 Months) [ Time Frame: Month 0-6 ]
    Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6.

  7. Consumption of Turoctocog Alfa for Bleeding Treatment: Average Dose to Treat a Bleed (24 Months) [ Time Frame: Month 0-24 ]
    Average dose of turoctocog alfa used to treat a bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24.

  8. Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (6 Months) [ Time Frame: Month 0-6 ]
    Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-6.

  9. Consumption of Turoctocog Alfa for Bleeding Treatment: Number of Injections Per Bleed (24 Months) [ Time Frame: Month 0-24 ]
    Number of turoctocog alfa injections consumed to treat a bleeding episode in both prophylaxis and on-demand regimen was evaluated during month 0-24.

  10. Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (6 Months) [ Time Frame: Month 0-6 ]
    Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-6.

  11. Consumption of Turoctocog Alfa for Bleeding Treatment: IU/kg Per Bleed (24 Months) [ Time Frame: Month 0-24 ]
    Consumption of turoctocog alfa IU/kg BW per bleed in both prophylaxis and on-demand regimen was evaluated during month 0-24.

  12. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (6 Months) [ Time Frame: Month 0-6 ]
    Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-6.

  13. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: Average Preventive Dose (24 Months) [ Time Frame: Month 0-24 ]
    Average preventive dose of turoctocog alfa consumed per participant in the prophylaxis regimen was evaluated during month 0-24.

  14. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (6 Months) [ Time Frame: Month 0-6 ]
    Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-6.

  15. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Month (24 Months) [ Time Frame: Month 0-24 ]
    Preventive dose of turoctocog alfa (IU/kg body weight (BW) per month) per participant in the prophylaxis regimen was evaluated during month 0-24.

  16. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (6 Months) [ Time Frame: Month 0-6 ]
    Preventive dose of turoctocog alfa (IU/kg body weight per year) per participant in the prophylaxis regimen was evaluated during month 0-6.

  17. Consumption of Turoctocog Alfa During Preventive Treatment Per Participant: IU/kg Per Year (24 Months) [ Time Frame: Month 0-24 ]
    Preventive dose of turoctocog alfa (IU/kg body weight (BW) per year) per participant in the prophylaxis regimen was evaluated during month 0-24.

  18. Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (6 Months) [ Time Frame: Month 0-6 ]
    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.

  19. Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Month (24 Months) [ Time Frame: Month 0-24 ]
    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.

  20. Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (6 Months) [ Time Frame: Month 0-6 ]
    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.

  21. Total Consumption of Turoctocog Alfa Per Participant: IU/kg Per Year (24 Months) [ Time Frame: Month 0-24 ]
    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.

  22. Frequency of Adverse Events (6 Months) [ Time Frame: Month 0-6 ]
    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.

  23. Frequency of Adverse Events (24 Months) [ Time Frame: Month 0-24 ]
    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.

  24. Frequency of Serious Adverse Events (6 Months) [ Time Frame: Month 0-6 ]
    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.

  25. Frequency of Serious Adverse Events (24 Months) [ Time Frame: Month 0-24 ]
    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.

  26. Haemostatic Effect of Turoctocog Alfa (Surgery): 6 Months [ Time Frame: Month 0-6 ]
    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.

  27. Haemostatic Effect of Turoctocog Alfa (Surgery): 24 Months [ Time Frame: Month 0-24 ]
    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.

  28. Loss of Blood (Surgery): 6 Months [ Time Frame: Month 0-6 ]
    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.

  29. Loss of Blood (Surgery): 24 Months [ Time Frame: Month 0-24 ]
    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.

  30. Requirements for Transfusion (Surgery): 6 Months [ Time Frame: Month 0-6 ]
    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.

  31. Requirements for Transfusion (Surgery): 24 Months [ Time Frame: Month 0-24 ]
    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.

  32. Adverse Events (Surgery): 6 Months [ Time Frame: Month 0-6 ]
    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.

  33. Adverse Events (Surgery): 24 Months [ Time Frame: Month 0-24 ]
    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.

  34. Serious Adverse Events (Surgery): 6 Months [ Time Frame: Month 0-6 ]
    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.

  35. Serious Adverse Events (Surgery): 24 Months [ Time Frame: Month 0-24 ]
    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.

  36. Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 6 [ Time Frame: Month 0, 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.

  37. Change in Total Scores for Reported Health-related Quality of Life (for Participants): Month 24 [ Time Frame: Month 0, 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.

  38. Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 6 [ Time Frame: Month 0, 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.

  39. Change in Total Scores for Reported Health-related Quality of Life (for Parents): Month 24 [ Time Frame: Month 0, 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.

  40. Incremental Recovery of FVIII [ Time Frame: Days 1-2 ]
    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.

  41. Area Under the Curve (AUC0-inf) [ Time Frame: Days 1-2 ]
    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.

  42. Half-life (t½) [ Time Frame: Days 1-2 ]
    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.

  43. Clearance (CL) [ Time Frame: Days 1-2 ]
    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.

  44. Highest Measured FVIII Activity in the Profile (Cmax) [ Time Frame: Days 1-2 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02938585


Locations
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China, Beijing
Novo Nordisk Investigational Site
Beijing, Beijing, China, 100045
China, Chongqing
Novo Nordisk Investigational Site
Chonqqing, Chongqing, China, 400014
China, Fujian
Novo Nordisk Investigational Site
Fuzhou, Fujian, China, 350001
China, Guangdong
Novo Nordisk Investigational Site
Guangzhou, Guangdong, China, 510515
China, Guizhou
Novo Nordisk Investigational Site
Guiyang, Guizhou, China, 550004
China, Hubei
Novo Nordisk Investigational Site
Wuhan, Hubei, China, 430030
China, Qinghai
Novo Nordisk Investigational Site
Xining, Qinghai, China, 810007
China, Shanghai
Novo Nordisk Investigational Site
Shanghai, Shanghai, China, 200025
China, Tianjin
Novo Nordisk Investigational Site
Tianjing, Tianjin, China, 300020
China, Yunnan
Novo Nordisk Investigational Site
Kunming, Yunnan, China, 650032
China, Zhejiang
Novo Nordisk Investigational Site
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] July 21, 2017
Statistical Analysis Plan  [PDF] November 1, 2018

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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT02938585    
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) )
First Posted: October 19, 2016    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Blood Coagulation Disorders, Inherited
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases
Factor VIII
Coagulants