A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors (explorer™4)
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| ClinicalTrials.gov Identifier: NCT03196284 |
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Recruitment Status :
Completed
First Posted : June 22, 2017
Last Update Posted : January 19, 2021
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Sponsor:
Novo Nordisk A/S
Information provided by (Responsible Party):
Novo Nordisk A/S
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Congenital Bleeding Disorder Haemophilia A With Inhibitors Haemophilia B With Inhibitors | Drug: Concizumab Drug: Eptacog alfa | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 26 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | August 10, 2017 |
| Actual Primary Completion Date : | September 19, 2018 |
| Actual Study Completion Date : | January 31, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hemophilia
Drug Information available for:
Recombinant FVIIa
| Arm | Intervention/treatment |
|---|---|
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Experimental: Concizumab
Concizumab administered in both the main phase and extension phase, with eptacog alfa administered on-demand during bleeding episodes
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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 |
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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
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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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
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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 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
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): NCT03196284
Locations
| 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, Iowa | |
| Novo Nordisk Investigational Site | |
| Iowa City, Iowa, United States, 52242 | |
| Austria | |
| Novo Nordisk Investigational Site | |
| Wien, Austria, 1090 | |
| Canada, Ontario | |
| Novo Nordisk Investigational Site | |
| Toronto, Ontario, Canada, M5B 1W8 | |
| Croatia | |
| Novo Nordisk Investigational Site | |
| Zagreb, Croatia, 10 000 | |
| Denmark | |
| Novo Nordisk Investigational Site | |
| Århus N, Denmark, 8200 | |
| Greece | |
| Novo Nordisk Investigational Site | |
| Athens, Greece, GR-11527 | |
| Israel | |
| Novo Nordisk Investigational Site | |
| Tel-Hashomer, Israel, 52621 | |
| Italy | |
| Novo Nordisk Investigational Site | |
| Firenze, Italy, 50134 | |
| Novo Nordisk Investigational Site | |
| Milano, Italy, 20124 | |
| Japan | |
| Novo Nordisk Investigational Site | |
| Aichi, Japan, 466-8560 | |
| Novo Nordisk Investigational Site | |
| Nara, Japan, 634-8522 | |
| Novo Nordisk Investigational Site | |
| Tokyo, Japan, 167-0035 | |
| Malaysia | |
| Novo Nordisk Investigational Site | |
| Georgetown, Penang, Malaysia, 10450 | |
| Novo Nordisk Investigational Site | |
| Kota Kinabalu, Malaysia, 88586 | |
| Spain | |
| Novo Nordisk Investigational Site | |
| Madrid, Spain, 28046 | |
| Novo Nordisk Investigational Site | |
| Sevilla, Spain, 41013 | |
| Sweden | |
| Novo Nordisk Investigational Site | |
| Solna, Sweden, 171 64 | |
| Ukraine | |
| Novo Nordisk Investigational Site | |
| Lviv, Ukraine, 79044 | |
| United Kingdom | |
| Novo Nordisk Investigational Site | |
| London, United Kingdom, SE1 7EH | |
| Novo Nordisk Investigational Site | |
| Sheffield, United Kingdom, S10 2JF | |
Sponsors and Collaborators
Novo Nordisk A/S
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novo Nordisk A/S |
| ClinicalTrials.gov Identifier: | NCT03196284 |
| Other Study ID Numbers: |
NN7415-4310 U1111-1179-2925 ( Other Identifier: World Health Organization (WHO) ) 2016-000510-30 ( EudraCT Number ) JapicCTI-173681 ( Registry Identifier: JAPIC ) |
| First Posted: | June 22, 2017 Key Record Dates |
| Last Update Posted: | January 19, 2021 |
| Last Verified: | January 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | According to disclosure commitment on novonordisk-trials.com |
| 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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Hemostatic Disorders Hemophilia A Hemophilia B Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Hematologic Diseases |
Coagulation Protein Disorders Hemorrhagic Disorders Genetic Diseases, Inborn Genetic Diseases, X-Linked Vascular Diseases Cardiovascular Diseases |