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A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors (explorer™4)

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: NCT03196284
Recruitment Status : Completed
First Posted : June 22, 2017
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Tracking Information
First Submitted Date  ICMJE June 20, 2017
First Posted Date  ICMJE June 22, 2017
Last Update Posted Date January 19, 2021
Actual Study Start Date  ICMJE August 10, 2017
Actual Primary Completion Date September 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
The number of bleeding episodes [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
The number of bleeding episodes that were treated during at least 24 weeks from treatment onset (week 0) are presented.
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
The number of bleeding episodes [ Time Frame: Week 0 - 24 ]
Count of episodes
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
  • The number of bleeding episodes [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    The number of bleeding episodes that were treated during at least 76 weeks from treatment onset (week 0) are presented.
  • The number of spontaneous bleeding episodes [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    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 (week 0) are presented.
  • The number of spontaneous bleeding episodes [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    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 (week 0) are presented.
  • Number of treatment-emergent adverse events (TEAEs) [ 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.
  • Number of treatment-emergent adverse events (TEAEs) [ 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.
  • Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Within 24 hours after eptacog alfa administration ]
    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 within 24 hours after eptacog alfa administration are presented.
  • Occurrence of anti-concizumab antibodies [ 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.
  • Occurrence of anti-concizumab antibodies [ 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.
  • Change in fibrinogen [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in fibrinogen during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in fibrinogen [ 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.
  • Change in D-dimer [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in D-dimer during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in D-dimer [ 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.
  • Change in prothrombin fragment 1 + 2 (F1 + 2) [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in F1 + 2 during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in prothrombin fragment 1 + 2 (F1 + 2) [ Time Frame: During at least 76 weeks from treatment onset (week 0) ]
    Change in F1 + 2 during at least 76 weeks from treatment onset (week 0) is presented.
  • Change in prothrombin time (PT) [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in PT during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in prothrombin time (PT) [ 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.
  • Change in activated partial thromboplastin time (APTT) [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in APTT during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in activated partial thromboplastin time (APTT) [ 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.
  • Change in anti-thrombin (AT) [ Time Frame: During at least 24 weeks from treatment onset (week 0) ]
    Change in AT during at least 24 weeks from treatment onset (week 0) is presented.
  • Change in anti-thrombin (AT) [ Time Frame: After at least 76 weeks from treatment onset (week 0) ]
    Change in AT after at least 76 weeks from treatment onset (week 0) is presented.
  • Concentration of concizumab [ 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.
  • Concentration of concizumab [ Time Frame: Prior to the last dose administration after atleast 76 weeks ]
    Concentration of concizumab prior to the last dose administration after atleast 76 weeks is presented.
  • Free Tissue Factor Pathway Inhibitor (TFPI) concentration value [ 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.
  • Free Tissue Factor Pathway Inhibitor (TFPI) concentration value [ Time Frame: Prior to the last dose administration after atleast 76 weeks ]
    Free TFPI concentration value prior to the last dose administration after atleast 76 weeks is presented.
  • Peak thrombin generation [ 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.
  • Peak thrombin generation [ Time Frame: Prior to the last dose administration after atleast 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 atleast 76 weeks is presented.
  • Endogenous thrombin potential [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Endogenous thrombin potential prior to the last dose administration at 24 weeks is presented.
  • Endogenous thrombin potential [ Time Frame: Prior to the last dose administration after atleast 76 weeks ]
    Endogenous thrombin potential prior to the last dose administration after atleast 76 weeks is presented.
  • Thrombin generation velocity index [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Thrombin generation velocity index prior to the last dose administration at 24 weeks is presented.
  • Thrombin generation velocity index [ Time Frame: Prior to the last dose administration after atleast 76 weeks ]
    Thrombin generation velocity index prior to the last dose administration after atleast 76 weeks is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
  • The number of bleeding episodes [ Time Frame: Week 0 - 76 ]
    Count of episodes
  • The number of spontaneous bleeding episodes [ Time Frame: Week 0 - 24 ]
    Count of episodes
  • The number of spontaneous bleeding episodes [ Time Frame: Week 0 - 76 ]
    Count of episodes
  • Number of treatment-emergent adverse events (TEAEs) [ Time Frame: Week 0 - 24 ]
    Count of events
  • Number of TEAEs [ Time Frame: Week 0 - 76 ]
    Count of events
  • Number of TEAEs [ Time Frame: 0 - 24 hours after eptacog alfa administration ]
    Count of events
  • Occurrence of anti-concizumab antibodies [ Time Frame: Week 0 - 24 ]
    Count of events
  • Occurrence of anti-concizumab antibodies [ Time Frame: Week 0 - 76 ]
    Count of events
  • Change in fibrinogen [ Time Frame: Week 0, week 24 ]
    Measured in g/L
  • Change in fibrinogen [ Time Frame: Week 0, week 76 ]
    Measured in g/L
  • Change in D-dimer [ Time Frame: Week 0, week 24 ]
    Measured in ng/ml
  • Change in D-dimer [ Time Frame: Week 0, week 76 ]
    Measured in ng/ml
  • Change in prothrombin fragment [ Time Frame: Week 0, week 24 ]
    Measured in pmol/L
  • Change in prothrombin fragment [ Time Frame: Week 0, week 76 ]
    Measured in pmol/L
  • Change in prothrombin time (PT) [ Time Frame: Week 0, week 24 ]
    Measured in seconds
  • Change in prothrombin time (PT) [ Time Frame: Week 0, week 76 ]
    Measured in seconds
  • Change in activated partial thromboplastin time (APTT) [ Time Frame: Week 0, week 24 ]
    Measured in seconds
  • Change in activated partial thromboplastin time (APTT) [ Time Frame: Week 0, week 76 ]
    Measured in seconds
  • Change in anti-thrombin (AT) [ Time Frame: Week 0, week 24 ]
    Measured in %
  • Change in anti-thrombin (AT) [ Time Frame: Week 0, week 76 ]
    Measured in %
  • Concentration of concizumab [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Measured in ng/ml
  • Concentration of concizumab [ Time Frame: Prior to the last dose administration at 76 weeks ]
    Measured in ng/ml
  • Free TFPI concentration value [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Measured in ng/ml
  • Free TFPI concentration value [ Time Frame: Prior to the last dose administration at 76 weeks ]
    Measured in ng/ml
  • Peak thrombin generation [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Measured in nM
  • Peak thrombin generation [ Time Frame: Prior to the last dose administration at 76 weeks ]
    Measured in nM
  • Endogenous thrombin potential [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Measured in nM x min
  • Endogenous thrombin potential [ Time Frame: Prior to the last dose administration at 76 weeks ]
    Measured in nM x min
  • Thrombin generation velocity index [ Time Frame: Prior to the last dose administration at 24 weeks ]
    Measured in nM/min
  • Thrombin generation velocity index [ Time Frame: Prior to the last dose administration at 76 weeks ]
    Measured in nM/min
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors
Official Title  ICMJE A Multi-Centre, Randomised, Open-Label, Controlled Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors
Brief Summary This trial is conducted in Africa, Asia, Europe and North America. 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 haemophilia A and B patients with inhibitors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Congenital Bleeding Disorder
  • Haemophilia A With Inhibitors
  • Haemophilia B With Inhibitors
Intervention  ICMJE
  • Drug: Concizumab
    A loading dose of 0.5 mg/kg will be given as the first dose, followed by 0.15 mg/kg (with potential stepwise dose escalation to 0.25 mg/kg) administered daily s.c. (subcutaneously, under the skin). Treatment duration is 24 weeks in the main trial, and up to 52 weeks in the extension phase
  • Drug: Eptacog alfa
    A single dose of 90 μg/kg eptacog alfa one week after dosing with concizumab. On-demand treatment during bleeding episodes in both treatment arms
Study Arms  ICMJE
  • Experimental: Concizumab
    Concizumab administered in both the main phase and extension phase, with eptacog alfa administered on-demand during bleeding episodes
    Interventions:
    • Drug: Concizumab
    • Drug: Eptacog alfa
  • Active Comparator: Eptacog alfa and concizumab
    Eptacog alfa administered on-demand during bleeding episodes as the only intervention during the main phase. Concizumab given in the extension phase
    Interventions:
    • Drug: Concizumab
    • Drug: Eptacog alfa
Publications * Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, Eichler H, Jiménez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood. 2019 Nov 28;134(22):1973-1982. doi: 10.1182/blood.2019001542.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2017)
26
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 31, 2020
Actual Primary Completion Date September 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE 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 haemophilia A or B patients with inhibitors aged 18 years or older at the time of signing informed consent - Patients currently in need of treatment with bypassing agents Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia - Ongoing or planned immune tolerance induction therapy or prophylaxis with FVIII or FIX
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Croatia,   Denmark,   Greece,   Israel,   Italy,   Japan,   Malaysia,   Spain,   Sweden,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03196284
Other Study ID Numbers  ICMJE NN7415-4310
U1111-1179-2925 ( Other Identifier: World Health Organization (WHO) )
2016-000510-30 ( EudraCT Number )
JapicCTI-173681 ( Registry Identifier: JAPIC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to disclosure commitment on novonordisk-trials.com
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novo Nordisk A/S
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP