A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors

Study Overview
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Brief Summary
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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.

Official Title
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A Multi-Centre Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients With Severe Haemophilia A Without Inhibitors

Conditions
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Haemostasis, Haemophilia A

Intervention / Treatment
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* Drug: Concizumab
* Drug: Turoctocog 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 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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concizumab<br>Daily administration of concizumab to both on-demand and prophylaxis patients | Drug: Concizumab<br>* 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<br>Drug: Turoctocog alfa<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Bleeding Episodes 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. | During at least 24 weeks from treatment onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Bleeding Episodes 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. | During at least 76 weeks from treatment onset | 
| The Number of Spontaneous Bleeding Episodes 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. | During at least 24 weeks from treatment onset | 
| The Number of Spontaneous Bleeding Episodes 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. | During at least 76 weeks from treatment onset | 
| 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 dose level participants were on at the time of onset of the adverse 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 dose level participants were on at the time of onset of the adverse event. | During at least 76 weeks from treatment onset (week 0) | 
| 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. 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. | 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. 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. | During at least 76 weeks from treatment onset (week 0) | 
| Change in Fibrinogen During 24 Weeks From Treatment Onset | 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. | During 24 weeks from treatment onset (week 0) | 
| Change in Fibrinogen During at Least 76 Weeks From Treatment Onset | 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 During 24 Weeks From Treatment Onset | 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 24 weeks from treatment onset (week 0) | 
| Change in D-dimer During at Least 76 Weeks From Treatment Onset | 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 + F2) During 24 Weeks From Treatment Onset | 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. | During 24 weeks from treatment onset (week 0) | 
| Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset | 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. | During at least 76 weeks from treatment onset (week 0) | 
| Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset | 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. | During 24 weeks from treatment onset (week 0) | 
| Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset | 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) During 24 Weeks From Treatment Onset | 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. | During 24 weeks from treatment onset (week 0) | 
| Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset | 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) During 24 Weeks From Treatment Onset | 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. | During 24 weeks from treatment onset (week 0) | 
| Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment | 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. | During at least 76 weeks from treatment onset (week 0) | 
| Concentration of Concizumab 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 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. | Prior to the last dose administration after at least 76 weeks | 
| Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value 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 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. | Prior to the last dose administration after at least 76 weeks | 
| Peak Thrombin Generation 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 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. | Prior to the last dose administration after at least 76 weeks | 
| Endogenous Thrombin Potential 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. | Prior to the last dose administration at 24 weeks | 
| Endogenous Thrombin Potential 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. | Prior to the last dose administration after at least 76 weeks | 
| Thrombin Generation Velocity Index 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. | Prior to the last dose administration at 24 weeks | 
| Thrombin Generation Velocity Index 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. | Prior to the last dose administration after at least 76 weeks |