A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients With Inhibitors

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Congenital Bleeding Disorder, Haemophilia A With Inhibitors, Haemophilia B With Inhibitors

Intervention / Treatment
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* Drug: Concizumab
* Drug: Eptacog alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concizumab<br>Concizumab administered in both the main phase and extension phase, with eptacog alfa administered on-demand during bleeding episodes | Drug: Concizumab<br>* 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<br>Drug: Eptacog alfa<br>* 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<br>|
| Active Comparator: Eptacog alfa and concizumab<br>Eptacog alfa administered on-demand during bleeding episodes as the only intervention during the main phase. Concizumab given in the extension phase | Drug: Concizumab<br>* 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<br>Drug: Eptacog alfa<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Bleeding Episodes | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Bleeding Episodes | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |