Haemophilia A, Haemostasis
Conditions
Brief summary
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.
Interventions
DRUGConcizumab
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
DRUGTuroctocog alfa
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
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 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. |
| The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 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. |
| Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset | 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 dose level participants were on at the time of onset of the adverse event. |
| Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset | 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 dose level participants were on at the time of onset of the adverse event. |
| Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset | 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. 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. |
| Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset | 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. 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. |
| Change in Fibrinogen During 24 Weeks From Treatment Onset | During 24 weeks from treatment onset (week 0) | 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. |
| Change in Fibrinogen During at Least 76 Weeks From Treatment Onset | 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. |
| Change in D-dimer During 24 Weeks From Treatment Onset | During 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. |
| Change in D-dimer During at Least 76 Weeks From Treatment Onset | 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. |
| Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset | During 24 weeks from treatment onset (week 0) | 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. |
| Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset | During at least 76 weeks from treatment onset (week 0) | 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. |
| Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset | During 24 weeks from treatment onset (week 0) | 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. |
| Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset | 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. |
| The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 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. |
| Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset | 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. |
| Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset | During 24 weeks from treatment onset (week 0) | 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. |
| Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment | During 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. |
| Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks | 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. |
| Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks | 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. |
| Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks | 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. |
| Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks | 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. |
| Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks | 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. |
| Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks | 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. |
| Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks | 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. |
| Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks | 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. |
| Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks | 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. |
| Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks | 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. |
| Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset | During 24 weeks from treatment onset (week 0) | 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. |
Countries
France, Germany, Italy, Japan, Spain, Sweden, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 26 sites in 11 countries as follows: France (3), Germany (2), Italy (1), Japan (3), Spain (3), Sweden (2), Thailand (1), Turkey (3), the United Kingdom (4), Ukraine (1) and the United States (3). In addition to these sites, 5 sites were approved by the IRB/IEC and/or local health authority but did not screen or assign any participants to treatment.
Pre-assignment details
The trial consisted of two treatment periods: main part which lasted at least 24 weeks for all participants in the trial and an extension part which was up to 102 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Concizumab Participants were to receive subcutaneous (s.c.) injection of concizumab once daily for up to 126 weeks (24 weeks main part + 52-102 weeks extension part). The initial dose was 0.15 milligrams per kilogram (mg/kg) and then the dose was escalated to 0.20 and 0.25 mg/kg based on the number of spontaneous bleeding episodes. Participants continued the extension phase at the same dose of concizumab once daily they have reached at the end of main part for 52-102 weeks with the potential dose escalation based on the number of spontaneous bleeding episodes. Breakthrough bleeding episodes occurring to the participants during the trial were treated with turoctocog at home. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Period | Lack of Efficacy | 2 |
| Extension Period | Withdrawal by Subject | 1 |
| Main Period | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Concizumab |
|---|---|
| Age, Continuous | 36.9 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants |
| Race/Ethnicity, Customized Not applicable | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 15 | 0 / 8 | 0 / 19 | 0 / 14 | 0 / 10 |
| other Total, other adverse events | 26 / 36 | 7 / 15 | 3 / 8 | 16 / 19 | 9 / 14 | 7 / 10 |
| serious Total, serious adverse events | 0 / 36 | 0 / 15 | 0 / 8 | 2 / 19 | 1 / 14 | 2 / 10 |
Outcome results
Primary
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.
Time frame: During at least 24 weeks from treatment onset
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 43 Episodes |
| Concizumab 0.20 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 13 Episodes |
| Concizumab 0.25 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 14 Episodes |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset | 1.5 sec | Standard Deviation 10.2 |
| Concizumab 0.20 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset | 3.1 sec | Standard Deviation 6.1 |
| Concizumab 0.25 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During 24 Weeks From Treatment Onset | 6.5 sec | Standard Deviation 6.9 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset | 3.1 sec | Standard Deviation 4.3 |
| Concizumab 0.20 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset | 9.2 sec | Standard Deviation 8.8 |
| Concizumab 0.25 mg/kg- Main Part | Change in Activated Partial Thromboplastin Time (APTT) During at Least 76 Weeks From Treatment Onset | 2.1 sec | Standard Deviation 9.4 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment | 0 second | Standard Deviation 12 |
| Concizumab 0.20 mg/kg- Main Part | Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment | 11 second | Standard Deviation 23 |
| Concizumab 0.25 mg/kg- Main Part | Change in Anti-thrombin (AT) After at Least 76 Weeks From Treatment | 15 second | Standard Deviation 25 |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset | 7 Percentage point | Standard Deviation 13 |
| Concizumab 0.20 mg/kg- Main Part | Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset | 17 Percentage point | Standard Deviation 31 |
| Concizumab 0.25 mg/kg- Main Part | Change in Anti-thrombin (AT) During 24 Weeks From Treatment Onset | 7 Percentage point | Standard Deviation 18 |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in D-dimer During 24 Weeks From Treatment Onset | 184.5 Nanograms per milliliter (ng/mL) | Standard Deviation 404.5 |
| Concizumab 0.20 mg/kg- Main Part | Change in D-dimer During 24 Weeks From Treatment Onset | 272.9 Nanograms per milliliter (ng/mL) | Standard Deviation 684.4 |
| Concizumab 0.25 mg/kg- Main Part | Change in D-dimer During 24 Weeks From Treatment Onset | 703.8 Nanograms per milliliter (ng/mL) | Standard Deviation 693.6 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in D-dimer During at Least 76 Weeks From Treatment Onset | 265.4 Nanograms per milliliter (ng/mL) | Standard Deviation 405.3 |
| Concizumab 0.20 mg/kg- Main Part | Change in D-dimer During at Least 76 Weeks From Treatment Onset | 506.7 Nanograms per milliliter (ng/mL) | Standard Deviation 369.9 |
| Concizumab 0.25 mg/kg- Main Part | Change in D-dimer During at Least 76 Weeks From Treatment Onset | 1109.3 Nanograms per milliliter (ng/mL) | Standard Deviation 818.5 |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Fibrinogen During 24 Weeks From Treatment Onset | -0.08 gram per litre (g/L) | Standard Deviation 0.61 |
| Concizumab 0.20 mg/kg- Main Part | Change in Fibrinogen During 24 Weeks From Treatment Onset | -0.19 gram per litre (g/L) | Standard Deviation 0.47 |
| Concizumab 0.25 mg/kg- Main Part | Change in Fibrinogen During 24 Weeks From Treatment Onset | -0.27 gram per litre (g/L) | Standard Deviation 0.29 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Fibrinogen During at Least 76 Weeks From Treatment Onset | -0.05 gram per litre (g/L) | Standard Deviation 0.39 |
| Concizumab 0.20 mg/kg- Main Part | Change in Fibrinogen During at Least 76 Weeks From Treatment Onset | -0.35 gram per litre (g/L) | Standard Deviation 0.56 |
| Concizumab 0.25 mg/kg- Main Part | Change in Fibrinogen During at Least 76 Weeks From Treatment Onset | -0.23 gram per litre (g/L) | Standard Deviation 0.63 |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset | 134 Picomoles per liter (pmol/L) | Standard Deviation 156 |
| Concizumab 0.20 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset | 257 Picomoles per liter (pmol/L) | Standard Deviation 524 |
| Concizumab 0.25 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During 24 Weeks From Treatment Onset | 580 Picomoles per liter (pmol/L) | Standard Deviation 741 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset | 128 pmol/L | Standard Deviation 183 |
| Concizumab 0.20 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset | 211 pmol/L | Standard Deviation 207 |
| Concizumab 0.25 mg/kg- Main Part | Change in Prothrombin Fragment 1 + 2 (F1 + F2) During at Least 76 Weeks From Treatment Onset | 889 pmol/L | Standard Deviation 423 |
Secondary
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.
Time frame: During 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset | -0.0 Seconds (sec) | Standard Deviation 0.4 |
| Concizumab 0.20 mg/kg- Main Part | Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset | -0.3 Seconds (sec) | Standard Deviation 0.9 |
| Concizumab 0.25 mg/kg- Main Part | Change in Prothrombin Time (PT) During 24 Weeks From Treatment Onset | 0.3 Seconds (sec) | Standard Deviation 0.7 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset | 0.0 sec | Standard Deviation 0.4 |
| Concizumab 0.20 mg/kg- Main Part | Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset | 0.8 sec | Standard Deviation 2.7 |
| Concizumab 0.25 mg/kg- Main Part | Change in Prothrombin Time (PT) During at Least 76 Weeks From Treatment Onset | 0.4 sec | Standard Deviation 0.4 |
Secondary
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.
Time frame: Prior to the last dose administration after at least 76 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks | 195.1 ng/mL | Standard Deviation 161.7 |
| Concizumab 0.20 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks | 392.3 ng/mL | Standard Deviation 427.9 |
| Concizumab 0.25 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration After at Least 76 Weeks | 4015.1 ng/mL | Standard Deviation 2902 |
Secondary
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.
Time frame: Prior to the last dose administration at 24 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks | 195.2 ng/mL | Standard Deviation 147 |
| Concizumab 0.20 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks | 374.4 ng/mL | Standard Deviation 644 |
| Concizumab 0.25 mg/kg- Main Part | Concentration of Concizumab Prior to the Last Dose Administration at 24 Weeks | 2640.8 ng/mL | Standard Deviation 4085.6 |
Secondary
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.
Time frame: Prior to the last dose administration after at least 76 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks | 1253.0 nM*min | Standard Deviation 507.3 |
| Concizumab 0.20 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks | 1352.6 nM*min | Standard Deviation 349.5 |
| Concizumab 0.25 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration After at Least 76 Weeks | 1233.4 nM*min | Standard Deviation 267.9 |
Secondary
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.
Time frame: Prior to the last dose administration at 24 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks | 1229.1 Nanomolar*minute (nM*min) | Standard Deviation 340.6 |
| Concizumab 0.20 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks | 965.3 Nanomolar*minute (nM*min) | Standard Deviation 362 |
| Concizumab 0.25 mg/kg- Main Part | Endogenous Thrombin Potential Prior to the Last Dose Administration at 24 Weeks | 1176.0 Nanomolar*minute (nM*min) | Standard Deviation 278.8 |
Secondary
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.
Time frame: Prior to the last dose administration after at least 76 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks | 26.9 ng/mL | Standard Deviation 17.1 |
| Concizumab 0.20 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks | 36.1 ng/mL | Standard Deviation 33.1 |
| Concizumab 0.25 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration After at Least 76 Weeks | 10.1 ng/mL | Standard Deviation 5.7 |
Secondary
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.
Time frame: Prior to the last dose administration at 24 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks | 30.1 ng/mL | Standard Deviation 15.6 |
| Concizumab 0.20 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks | 64.4 ng/mL | Standard Deviation 35.3 |
| Concizumab 0.25 mg/kg- Main Part | Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Value Prior to the Last Dose Administration at 24 Weeks | 12.4 ng/mL | Standard Deviation 2.2 |
Secondary
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.
Time frame: During at least 24 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset | 105 Events |
| Concizumab 0.20 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset | 16 Events |
| Concizumab 0.25 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 24 Weeks From Treatment Onset | 9 Events |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The SAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset | 201 Events |
| Concizumab 0.20 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset | 53 Events |
| Concizumab 0.25 mg/kg- Main Part | Number of Treatment-emergent Adverse Events (TEAEs) During at Least 76 Weeks From Treatment Onset | 44 Events |
Secondary
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.
Time frame: During at least 24 weeks from treatment onset (week 0)
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset | Yes | 3 Participants |
| Concizumab 0.15 mg/kg- Main Part | Occurrence of Anti-concizumab Antibodies During at Least 24 Weeks From Treatment Onset | No | 33 Participants |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset (week 0)
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset | Yes | 9 Participants |
| Concizumab 0.15 mg/kg- Main Part | Occurrence of Anti-concizumab Antibodies During at Least 76 Weeks From Treatment Onset | No | 27 Participants |
Secondary
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.
Time frame: Prior to the last dose administration after at least 76 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks | 90.8 nmol/L | Standard Deviation 45.2 |
| Concizumab 0.20 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks | 99.1 nmol/L | Standard Deviation 36.2 |
| Concizumab 0.25 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration After at Least 76 Weeks | 111.6 nmol/L | Standard Deviation 63.5 |
Secondary
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.
Time frame: Prior to the last dose administration at 24 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks | 88.6 Nanomoles per liter (nmol/L) | Standard Deviation 34.5 |
| Concizumab 0.20 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks | 67.5 Nanomoles per liter (nmol/L) | Standard Deviation 35 |
| Concizumab 0.25 mg/kg- Main Part | Peak Thrombin Generation Prior to the Last Dose Administration at 24 Weeks | 83.4 Nanomoles per liter (nmol/L) | Standard Deviation 10.6 |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 67 Episodes |
| Concizumab 0.20 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 42 Episodes |
| Concizumab 0.25 mg/kg- Main Part | The Number of Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 123 Episodes |
Secondary
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.
Time frame: During at least 24 weeks from treatment onset
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 16 Episodes |
| Concizumab 0.20 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 8 Episodes |
| Concizumab 0.25 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 24 Weeks From Treatment Onset | 2 Episodes |
Secondary
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.
Time frame: During at least 76 weeks from treatment onset
Population: The FAS included all participants who took al least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 39 Episodes |
| Concizumab 0.20 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 15 Episodes |
| Concizumab 0.25 mg/kg- Main Part | The Number of Spontaneous Bleeding Episodes During at Least 76 Weeks From Treatment Onset | 29 Episodes |
Secondary
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.
Time frame: Prior to the last dose administration after at least 76 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks | 10.3 Nano molar/min (nM/min) | Standard Deviation 6.4 |
| Concizumab 0.20 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks | 10.5 Nano molar/min (nM/min) | Standard Deviation 4.8 |
| Concizumab 0.25 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration After at Least 76 Weeks | 16.0 Nano molar/min (nM/min) | Standard Deviation 17.1 |
Secondary
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.
Time frame: Prior to the last dose administration at 24 weeks
Population: The FAS included all participants who took al least one dose of the study drug. Overall number of participants analysed = number of participants with available data at the last dose level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Concizumab 0.15 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks | 9.3 nM/min | Standard Deviation 4.8 |
| Concizumab 0.20 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks | 7.0 nM/min | Standard Deviation 5 |
| Concizumab 0.25 mg/kg- Main Part | Thrombin Generation Velocity Index Prior to the Last Dose Administration at 24 Weeks | 8.2 nM/min | Standard Deviation 1.6 |