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A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors (explorer™5)

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ClinicalTrials.gov Identifier: NCT03196297
Recruitment Status : Completed
First Posted : June 22, 2017
Results First Posted : May 10, 2021
Last Update Posted : November 16, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is conducted in Asia, Europe and the United States of America (USA). The aim of the trial is to assess the efficacy of concizumab administered s.c. (subcutaneously, under the skin) once daily in preventing bleeding episodes in patients with severe haemophilia A without inhibitors.

Condition or disease Intervention/treatment Phase
Haemostasis Haemophilia A Drug: Concizumab Drug: Turoctocog alfa Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Centre Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors
Actual Study Start Date : August 16, 2017
Actual Primary Completion Date : June 22, 2018
Actual Study Completion Date : June 3, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Experimental: Concizumab
Daily administration of concizumab to both on-demand and prophylaxis patients
Drug: Concizumab
0.15 mg/kg (with potential stepwise dose administration to 0.25 mg/kg) administered daily s.c (subcutaneously, under the skin). Treatment duration is 24 weeks in the main phase, and 52 weeks in the extension phase

Drug: Turoctocog alfa
Breakthrough bleeding episodes will be treated by the patients at home with turoctocog alfa at the discretion of the study doctor, who will also choose dose levels




Primary Outcome Measures :
  1. The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset [ Time Frame: During at least 24 weeks from treatment onset ]
    The number of bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.


Secondary Outcome Measures :
  1. The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset ]
    The number of bleeding episodes that were treated during at least 76 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.

  2. The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset [ Time Frame: During at least 24 weeks from treatment onset ]
    Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.

  3. The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset ]
    Bleeds that were not linked to a specific, known action or event are called spontaneous bleeding episodes. The number of spontaneous bleeding episodes that were treated during at least 76 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.

  4. Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 24 weeks from treatment onset (week 0) are presented. The data is presented per dose level participants were on at the time of onset of the adverse event.

  5. Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily had a causal relationship with this treatment. A TEAE was defined as an event that had onset from the first exposure to treatment until the last visit in the trial. Number of TEAEs that occurred during at least 76 weeks from treatment onset (week 0) are presented. The data is presented per dose level participants were on at the time of onset of the adverse event.

  6. Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Occurrence of anti-concizumab antibodies during at least 24 weeks from treatment onset (week 0) is presented. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.

  7. Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Occurrence of anti-concizumab antibodies during at least 76 weeks from treatment onset (week 0) is presented. In the reported data, 'Yes' infers number of participants who showed positive anti-concizumab antibody tests whereas 'No' infers number of participants who showed negative anti-concizumab antibody tests.

  8. Change in Fibrinogen During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in fibrinogen during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  9. Change in Fibrinogen During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in fibrinogen during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  10. Change in D-dimer During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in D-dimer during at least 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  11. Change in D-dimer During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in D-dimer during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  12. Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in F1 + F2 during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  13. Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in F1 + F2 during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  14. Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in PT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  15. Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in PT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  16. Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in APTT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  17. Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in APTT during at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  18. Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset [ Time Frame: During 24 weeks from treatment onset (week 0) ]
    Change in AT during 24 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  19. Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in AT after at least 76 weeks from treatment onset (week 0) is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  20. Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Concentration of concizumab prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  21. Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks [ Time Frame: Prior to the last dose administration after at least 76 weeks ]
    Concentration of concizumab prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  22. Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Free TFPI (TFPI not bound to concizumab) concentration value prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  23. Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks [ Time Frame: Prior to the last dose administration after at least 76 weeks ]
    Free TFPI concentration value prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  24. Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  25. Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks [ Time Frame: Prior to the last dose administration after at least 76 weeks ]
    Peak thrombin generation is the maximal concentration of thrombin formed at a given point in time. Peak thrombin generation prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  26. Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks [ Time Frame: Prior to the last dose administration at 24 weeks ]
    The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. Endogenous thrombin potential prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  27. Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks [ Time Frame: Prior to the last dose administration after at least 76 weeks ]
    The endogenous thrombin potential (ETP), defined as the amount of thrombin which can be generated after the in vitro activation of coagulation with tissue factor as trigger and phospholipids as platelet substitute. Endogenous thrombin potential prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  28. Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. Thrombin generation velocity index prior to the last dose administration at 24 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.

  29. Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks [ Time Frame: Prior to the last dose administration after at least 76 weeks ]
    Thrombin generation velocity index represents the effective rate of thrombin generation between lag time and time to peak. Thrombin generation velocity index prior to the last dose administration after at least 76 weeks is presented. The data is presented per the last dose level which the participants have reached at the time of assessment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine the suitability for the trial - Male patients aged 18 years or older at the time of signing informed consent, diagnosed with severe haemophilia A (FVIII activity below 1%), based on medical records or results at screening Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia A - Presence of inhibitors (neutralising antibodies) to Factor VIII (equal to or above 0.6 Bethesda Units) at screening measured by the Nijmegen method

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): NCT03196297


Locations
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United States, California
Novo Nordisk Investigational Site
Los Angeles, California, United States, 90027
United States, Indiana
Novo Nordisk Investigational Site
Indianapolis, Indiana, United States, 46260
United States, Oklahoma
Novo Nordisk Investigational Site
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Novo Nordisk Investigational Site
Nashville, Tennessee, United States, 37232
United States, Utah
Novo Nordisk Investigational Site
Salt Lake City, Utah, United States, 84113
France
Novo Nordisk Investigational Site
Brest, France, 29609
Novo Nordisk Investigational Site
Caen, France, 14033
Novo Nordisk Investigational Site
Nantes Cedex 1, France, 44093
Germany
Novo Nordisk Investigational Site
Bonn, Germany, 53127
Novo Nordisk Investigational Site
Homburg, Germany, 66421
Italy
Novo Nordisk Investigational Site
Milano, Italy, 20124
Novo Nordisk Investigational Site
Rome, Italy, 00168
Japan
Novo Nordisk Investigational Site
Aichi, Japan, 466-8560
Novo Nordisk Investigational Site
Nara, Japan, 634-8522
Novo Nordisk Investigational Site
Tokyo, Japan, 160-0023
Novo Nordisk Investigational Site
Tokyo, Japan, 167-0035
Spain
Novo Nordisk Investigational Site
Madrid, Spain, 28046
Novo Nordisk Investigational Site
Málaga, Spain, 29010
Novo Nordisk Investigational Site
Valencia, Spain, 46026
Sweden
Novo Nordisk Investigational Site
Malmö, Sweden, 205 02
Novo Nordisk Investigational Site
Solna, Sweden, 171 64
Thailand
Novo Nordisk Investigational Site
Bangkok, Thailand, 10400
Turkey
Novo Nordisk Investigational Site
Ankara, Turkey, 06100
Novo Nordisk Investigational Site
Bornova-IZMIR, Turkey, 35100
Novo Nordisk Investigational Site
Edirne, Turkey, 22030
Novo Nordisk Investigational Site
İstanbul, Turkey, 34098
Ukraine
Novo Nordisk Investigational Site
Lviv, Ukraine, 79044
United Kingdom
Novo Nordisk Investigational Site
Belfast, United Kingdom, BT9 7AB
Novo Nordisk Investigational Site
Cambridge, United Kingdom, CB2 0QQ
Novo Nordisk Investigational Site
London, United Kingdom, NW3 2QG
Novo Nordisk Investigational Site
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] August 28, 2018
Statistical Analysis Plan  [PDF] July 13, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03196297    
Other Study ID Numbers: NN7415-4255
U1111-1179-3872 ( Other Identifier: World Health Organization (WHO) )
2016-000614-29 ( Registry Identifier: EudraCT )
JapicCTI-173682 ( Registry Identifier: JAPIC )
First Posted: June 22, 2017    Key Record Dates
Results First Posted: May 10, 2021
Last Update Posted: November 16, 2021
Last Verified: November 2021
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: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn