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

September 24, 2021 updated by: Novo Nordisk A/S

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria, 1090
        • Novo Nordisk Investigational Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5B 1X1
        • Novo Nordisk Investigational Site
  • Croatia
      • Zagreb, Croatia, 10 000
        • Novo Nordisk Investigational Site
  • Denmark
      • Århus N, Denmark, 8200
        • Novo Nordisk Investigational Site
  • Greece
      • Athens, Greece, GR-11527
        • Novo Nordisk Investigational Site
  • Israel
      • Tel-Hashomer, Israel, 52621
        • Novo Nordisk Investigational Site
  • Italy
      • Firenze, Italy, 50134
        • Novo Nordisk Investigational Site
      • Milano, Italy, 20124
        • Novo Nordisk Investigational Site
  • Japan
      • Aichi, Japan, 466-8560
        • Novo Nordisk Investigational Site
      • Nara, Japan, 634-8522
        • Novo Nordisk Investigational Site
      • Tokyo, Japan, 167-0035
        • Novo Nordisk Investigational Site
  • Malaysia
      • Georgetown, Penang, Malaysia, 10450
        • Novo Nordisk Investigational Site
      • Kota Kinabalu, Malaysia, 88586
        • Novo Nordisk Investigational Site
  • Spain
      • Madrid, Spain, 28046
        • Novo Nordisk Investigational Site
      • Sevilla, Spain, 41013
        • Novo Nordisk Investigational Site
  • Sweden
      • Solna, Sweden, 171 64
        • Novo Nordisk Investigational Site
  • Ukraine
      • Lviv, Ukraine, 79044
        • Novo Nordisk Investigational Site
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Novo Nordisk Investigational Site
      • Sheffield, United Kingdom, S10 2JF
        • Novo Nordisk Investigational Site
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Novo Nordisk Investigational Site
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Novo Nordisk Investigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Novo Nordisk Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Concizumab
Concizumab administered in both the main phase and extension phase, with eptacog alfa administered on-demand during bleeding episodes
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
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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
During at least 24 weeks from treatment onset (week 0)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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. This outcome measure is applicable for only 'Concizumab' treatment arm.
During at least 76 weeks from treatment onset (week 0)
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 data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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 the dose level which the participants have reached at the time of event.
During at least 24 weeks from treatment onset (week 0)
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 the dose level which the participants have reached at the time of event.
During at least 76 weeks from treatment onset (week 0)
Number of Treatment-emergent Adverse Events (TEAEs) Within 24 Hours After Eptacog Alfa Administration
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. This outcome measure is applicable only for 'Eptacog alfa' treatment arm.
Within 24 hours after eptacog alfa administration
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. This outcome measure is applicable for only 'Concizumab' treatment arm.
During at least 24 weeks from treatment onset (week 0)
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. This outcome measure is applicable for only 'Concizumab' treatment arm.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
During at least 24 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
After at least 76 weeks from treatment onset (week 0)
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration at 24 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration after atleast 76 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration at 24 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration after atleast 76 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration at 24 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration after atleast 76 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration at 24 weeks
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 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.
Prior to the last dose administration after atleast 76 weeks
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. The data is presented per the last dose level which the participants have reached at the time of assessment.
Prior to the last dose administration at 24 weeks
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 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.
Prior to the last dose administration after atleast 76 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novo Nordisk A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 10, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 19, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NN7415-4310
  • U1111-1179-2925 (OTHER: World Health Organization (WHO))
  • 2016-000510-30 (EUDRACT_NUMBER)
  • JapicCTI-173681 (REGISTRY: JAPIC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

According to disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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