Acquired Thrombotic Thrombocytopenic Purpura
Conditions
Brief summary
This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP. Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).
Interventions
BIOLOGICALCaplacizumab
* Subjects received a first intravenous (i.v.) bolus of 10 mg (filled at 5 mg/mL) caplacizumab via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session). * The first PE on study was followed by subcutaneous (s.c.) administration of 10 mg study drug within 30 minutes after the end of the PE procedure. * All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose. * Subjects received caplacizumab up to 30 days after the last PE session.
BIOLOGICALPlacebo
* Subjects received a first i.v. bolus of placebo via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session). * The first PE on study was followed by s.c. administration of placebo within 30 minutes after the end of the PE procedure. * All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose. * Subjects received placebo up to 30 days after the last PE session.
Sponsors
Ablynx, a Sanofi company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
A single-blinded study design was initiated because, in the initial versions of the protocol, the dosing regimen could be adjusted dependent on the results of the Ristocetin Cofactor (RICO) test following the initial dose. Therefore, a double-blind design was not feasible because the results of the RICO test effectively unblinded the Investigator. Single-blind design was maintained due to the objective nature of the primary endpoint.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older (adults) or aged 12 to \< 18 years (adolescents) * Male or female subject, willing to accept an acceptable contraceptive regimen * Subject with a clinical diagnosis of TTP * Requiring PE (one single PE session prior to randomization into the study was allowed) * Subject accessible to follow-up * Subject able to provide signed and dated informed consent and assent (if applicable, for adolescents)
Exclusion criteria
* Platelet count ≥ 100,000/µL * Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) * Clinical evidence of enteric infection with Escherichia coli 0157 or related organism * Anti-phospholipid syndrome * Diagnosis of disseminated intravascular coagulation (DIC) * Pregnancy or breast-feeding * Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy * Known with congenital TTP * Active bleeding or high risk of bleeding * Uncontrolled arterial hypertension * Known chronic treatment with anticoagulant treatment that cannot be stopped safely, including but not limited to: * vitamin K antagonists * heparin or low molecular weight heparin (LMWH) * non-acetyl salicylic acid non-steroidal anti-inflammatory molecules * Severe or life threatening clinical condition other than TTP that would impair participation in the study * Subjects with malignancies resulting in a life expectation of less than 3 months * Subjects with known or suspected bone marrow carcinosis * Subjects who cannot comply with study protocol requirements and procedures * Known hypersensitivity to the active substance or to excipients of the study drug * Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows: * bilirubin \> 3 x upper limit of normal (ULN) (needed to differentiate isolated increase in indirect bilirubin due to hemolysis, this was not an exclusion parameter but disease-related) * alanine transaminase (ALT)/ aspartate transaminase (AST) \> 5 x ULN * alkaline phosphatase (ALP) \> 5 x ULN * gamma-glutamyl transpeptidase (GGT) \> 5 x ULN * Severe chronic renal impairment, as defined by glomerular filtration rate \< 30 mL/min Note that the use of another investigational drug or device within 30 days prior to screening was not allowed. Participation in non-interventional/observational studies and registries during the study period was allowed. Participation in another clinical study was not allowed until the end of the follow-up period or within 30 days after the last study treatment in case of early subject withdrawal from the study. Subjects who had already participated in the current study and had either completed the study per protocol or had discontinued prematurely, were not allowed to be re-included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | From the day of first study drug administration up to 30 days after first study drug administration | Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response'). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects With Exacerbations of TTP | Within 30 days of last day of initial daily PE | Number and percentage of subjects with exacerbations of TTP (defined as recurrent thrombocytopenia following a confirmed platelet count response and requiring a re-initiation of daily PE treatment after ≥ 1 day but ≤ 30 days of end of daily PE treatment. Time to first exacerbation of TTP was also examined as part of this end point analysis; the median time to first exacerbation could not be determined because of the small number of events. |
| Number and Percentage of Subjects With Relapse of TTP | Later than 30 days after the last daily PE | Number and percentage of subjects with relapse of TTP (defined as de novo TTP event that occurred later than 30 days after the last daily PE) was evaluated. |
| Number of Daily PE Sessions During the Initial Daily PE Period | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days | Number of daily PE sessions during the initial daily PE period which could include more than 1 PE per day was evaluated. |
| Total Volume of Plasma Administered During the Initial Daily PE Period | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days | The total volume of plasma administered during the initial daily PE period was measured. |
| Number of Days With at Least One PE Administration During the Total Course of the Study | During the total course of the study (from Screening till the 12-month follow-up [FU] visit) | Number of days for PE was evaluated. This implies the number of days with at least one PE administration during the total course of the study. |
| The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days | The maximum number of consecutive days per subject where there was no interruption of PE during the initial daily PE period. |
| Resolution of Non-focal Neurological Symptoms | From Baseline till the 12-month FU visit | Resolution of non-focal neurological symptoms as defined by neurocognitive function at complete remission, measured by a Computerised Neuropsychological Test Battery(CNTB) (adults only). The CNTB included 6 modules: word list learning and selective reminding (WLL/SR), choice reaction time (CRT), visual memory (VMEM), simple reaction time (SRT), working memory (WMEM), and word list learning and delayed recall (WLL/DR). The 6 tasks are rated as a percentage correct (for CRT and SRT, the percentage correct corresponds to the percentage hits) and the mean score from these provides the CNTB summary score (range: 0-100). A higher CNTB summary score indicates better neuropsychological functioning. |
| Number of Participants With Resolution of TTP-related Signs or Symptoms | End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up | Resolution or improvement (improvement of ≥ 1 grade in the Common Terminology Criteria for Adverse Events \[CTCAE\] v4.0 scale) of TTP-related signs and symptoms as captured on physical examination and as adverse events. This endpoint was only evaluated for resolution. |
| Mortality | From the start of the study up to 1 month follow-up | Total mortality up to 1 month follow-up. |
| Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE) | From the day of first study drug administration up to 30 days after first study drug administration | Number and percentage of subjects with complete remission (defined as confirmed platelet count response and absence of exacerbation) following initial daily PE. |
| Number and Percentage of Subjects With PE Related AEs | From the start of the study up to 1 month follow-up | Number and percentage of subjects with PE related AEs. |
| Number of Treatment-emergent Adverse Events (TEAEs) by Severity | From the start of the study up to 1 month follow-up | Number and severity of TEAEs were evaluated. The severity grades of AEs were defined as: mild, moderate, and severe. Note: the numbers listed do not include the TEAEs with missing severity. |
| Number and Percentage of Subjects With TEAEs by Severity | From the start of the study up to 1 month follow-up | Number and percentage of subjects with TEAEs by severity. The severity grades of AEs were defined as: mild, moderate, and severe. |
| Number of TEAEs and Their Relationship to Study Drug | From the start of the study up to 1 month follow-up | Number of TEAEs and their relationship to study drug were evaluated. Relationship of AEs to study drug was: related, possibly related, and unlikely/not related. |
| Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA) | From the start of the study until last follow-up visit | The development of anti-drug antibodies (ADA) was monitored from the start of the study until last follow-up visit. |
| Plasma Concentrations of Caplacizumab | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). | The concentration of caplacizumab in plasma was determined at different time points. pharmacokinetics (PK) Population: the PK Population consisted of all subjects who received the study drug and for whom the primary PK data are considered to be sufficient and interpretable. |
| Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). | The change from baseline in RICO activity was measured at different time points. |
| Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). | The change from baseline in vWF:Ag concentration was measured at different time points. |
| PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). | The change from baseline in FVIII:C concentration was measured at different ime points. |
| Number of PE Related Adverse Events | From the start of the study up to 1 month follow-up | Number of PE treatment-related adverse events (AEs). |
Countries
Australia, Austria, Belgium, Bulgaria, France, Germany, Israel, Italy, Romania, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Subjects with aTTP were recruited from 11 countries in Europe, Australia, Asia and United States (US). Only adults were recruited; no adolescent patients were enrolled, although the trial was open for adolescent patients. A total of 75 patients were included in the trial.
Pre-assignment details
76 subjects were screened, 75 subjects were randomized (= Intent-to-treat \[ITT\] population): 36 in the ALX-0081 group, 39 in the placebo group.
Participants by arm
| Arm | Count |
|---|---|
| Caplacizumab Caplacizumab:
* Subjects received a first i.v. bolus of 10 mg (filled at 5 mg/mL) caplacizumab via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
* The first PE on study was followed by s.c. administration of 10 mg study drug within 30 minutes after the end of the PE procedure.
* All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
* Subjects received caplacizumab up to 30 days after the last PE session. | 36 |
| Placebo Placebo:
* Subjects received a first i.v. bolus of placebo via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
* The first PE on study was followed by s.c. administration of placebo within 30 minutes after the end of the PE procedure.
* All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
* Subjects received placebo up to 30 days after the last PE session. | 39 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Diagnosed as non-TTP patient | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Participated in other clinical trial | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Study terminated by Sponsor | 9 | 10 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Caplacizumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 38 Participants | 73 Participants |
| Age, Continuous | 40.6 years STANDARD_DEVIATION 12.7 | 42.5 years STANDARD_DEVIATION 13.18 | 41.6 years STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized Race/Ethnicity Black | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 32 Participants | 34 Participants | 66 Participants |
| Sex: Female, Male Female | 24 Participants | 20 Participants | 44 Participants |
| Sex: Female, Male Male | 12 Participants | 19 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 2 / 37 |
| other Total, other adverse events | 33 / 35 | 37 / 37 |
| serious Total, serious adverse events | 20 / 35 | 19 / 37 |
Outcome results
Primary
Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL
Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response').
Time frame: From the day of first study drug administration up to 30 days after first study drug administration
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Caplacizumab | Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | YES - One PE session prior to randomization | 2.4 days |
| Caplacizumab | Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | NO - No PE session prior to randomization | 3 days |
| Placebo | Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | YES - One PE session prior to randomization | 4.3 days |
| Placebo | Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | NO - No PE session prior to randomization | 4.9 days |
Comparison: The primary analysis consisted of a Kaplan-Meier analysis with time-to-response as endpoint and treatment group as the independent variable and stratified for absence/presence of one PE session prior to randomization.p-value: =0.00595% CI: [1.28, 3.78]Stratified log-rank test
Secondary
Mortality
Total mortality up to 1 month follow-up.
Time frame: From the start of the study up to 1 month follow-up
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Mortality | 0 Participants |
| Placebo | Mortality | 2 Participants |
Secondary
Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE)
Number and percentage of subjects with complete remission (defined as confirmed platelet count response and absence of exacerbation) following initial daily PE.
Time frame: From the day of first study drug administration up to 30 days after first study drug administration
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE) | 29 Participants |
| Placebo | Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE) | 18 Participants |
Secondary
Number and Percentage of Subjects With Exacerbations of TTP
Number and percentage of subjects with exacerbations of TTP (defined as recurrent thrombocytopenia following a confirmed platelet count response and requiring a re-initiation of daily PE treatment after ≥ 1 day but ≤ 30 days of end of daily PE treatment. Time to first exacerbation of TTP was also examined as part of this end point analysis; the median time to first exacerbation could not be determined because of the small number of events.
Time frame: Within 30 days of last day of initial daily PE
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Number and Percentage of Subjects With Exacerbations of TTP | 3 Participants |
| Placebo | Number and Percentage of Subjects With Exacerbations of TTP | 11 Participants |
Secondary
Number and Percentage of Subjects With PE Related AEs
Number and percentage of subjects with PE related AEs.
Time frame: From the start of the study up to 1 month follow-up
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Number and Percentage of Subjects With PE Related AEs | 20 Participants |
| Placebo | Number and Percentage of Subjects With PE Related AEs | 20 Participants |
Secondary
Number and Percentage of Subjects With Relapse of TTP
Number and percentage of subjects with relapse of TTP (defined as de novo TTP event that occurred later than 30 days after the last daily PE) was evaluated.
Time frame: Later than 30 days after the last daily PE
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Number and Percentage of Subjects With Relapse of TTP | 11 Participants |
| Placebo | Number and Percentage of Subjects With Relapse of TTP | 3 Participants |
Secondary
Number and Percentage of Subjects With TEAEs by Severity
Number and percentage of subjects with TEAEs by severity. The severity grades of AEs were defined as: mild, moderate, and severe.
Time frame: From the start of the study up to 1 month follow-up
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Caplacizumab | Number and Percentage of Subjects With TEAEs by Severity | Mild | 31 Participants |
| Caplacizumab | Number and Percentage of Subjects With TEAEs by Severity | Moderate | 27 Participants |
| Caplacizumab | Number and Percentage of Subjects With TEAEs by Severity | Severe | 18 Participants |
| Placebo | Number and Percentage of Subjects With TEAEs by Severity | Mild | 36 Participants |
| Placebo | Number and Percentage of Subjects With TEAEs by Severity | Moderate | 31 Participants |
| Placebo | Number and Percentage of Subjects With TEAEs by Severity | Severe | 14 Participants |
Secondary
Number of Daily PE Sessions During the Initial Daily PE Period
Number of daily PE sessions during the initial daily PE period which could include more than 1 PE per day was evaluated.
Time frame: During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Population: Number of subjects from the ITT Population with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Caplacizumab | Number of Daily PE Sessions During the Initial Daily PE Period | 6.7 PE sessions | Standard Deviation 3.69 |
| Placebo | Number of Daily PE Sessions During the Initial Daily PE Period | 8.4 PE sessions | Standard Deviation 6.74 |
Secondary
Number of Days With at Least One PE Administration During the Total Course of the Study
Number of days for PE was evaluated. This implies the number of days with at least one PE administration during the total course of the study.
Time frame: During the total course of the study (from Screening till the 12-month follow-up [FU] visit)
Population: Number of subjects from the ITT Population with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Caplacizumab | Number of Days With at Least One PE Administration During the Total Course of the Study | 11.8 days | Standard Deviation 7.43 |
| Placebo | Number of Days With at Least One PE Administration During the Total Course of the Study | 12.6 days | Standard Deviation 9.15 |
Secondary
Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA)
The development of anti-drug antibodies (ADA) was monitored from the start of the study until last follow-up visit.
Time frame: From the start of the study until last follow-up visit
Population: Number of subjects from the Safety Population with data available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caplacizumab | Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA) | 3 Participants |
| Placebo | Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA) | 0 Participants |
Secondary
Number of Participants With Resolution of TTP-related Signs or Symptoms
Resolution or improvement (improvement of ≥ 1 grade in the Common Terminology Criteria for Adverse Events \[CTCAE\] v4.0 scale) of TTP-related signs and symptoms as captured on physical examination and as adverse events. This endpoint was only evaluated for resolution.
Time frame: End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Caplacizumab | Number of Participants With Resolution of TTP-related Signs or Symptoms | End of daily PE treatment period | 29 Participants |
| Caplacizumab | Number of Participants With Resolution of TTP-related Signs or Symptoms | End of study treatment period | 30 Participants |
| Caplacizumab | Number of Participants With Resolution of TTP-related Signs or Symptoms | At 1 month follow-up | 31 Participants |
| Placebo | Number of Participants With Resolution of TTP-related Signs or Symptoms | End of daily PE treatment period | 29 Participants |
| Placebo | Number of Participants With Resolution of TTP-related Signs or Symptoms | End of study treatment period | 33 Participants |
| Placebo | Number of Participants With Resolution of TTP-related Signs or Symptoms | At 1 month follow-up | 27 Participants |
Secondary
Number of PE Related Adverse Events
Number of PE treatment-related adverse events (AEs).
Time frame: From the start of the study up to 1 month follow-up
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caplacizumab | Number of PE Related Adverse Events | 72 adverse events |
| Placebo | Number of PE Related Adverse Events | 44 adverse events |
Secondary
Number of TEAEs and Their Relationship to Study Drug
Number of TEAEs and their relationship to study drug were evaluated. Relationship of AEs to study drug was: related, possibly related, and unlikely/not related.
Time frame: From the start of the study up to 1 month follow-up
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Caplacizumab | Number of TEAEs and Their Relationship to Study Drug | Related | 12 adverse events |
| Caplacizumab | Number of TEAEs and Their Relationship to Study Drug | Possibly related | 59 adverse events |
| Caplacizumab | Number of TEAEs and Their Relationship to Study Drug | Unlikely/not related | 486 adverse events |
| Placebo | Number of TEAEs and Their Relationship to Study Drug | Related | 6 adverse events |
| Placebo | Number of TEAEs and Their Relationship to Study Drug | Possibly related | 9 adverse events |
| Placebo | Number of TEAEs and Their Relationship to Study Drug | Unlikely/not related | 524 adverse events |
Secondary
Number of Treatment-emergent Adverse Events (TEAEs) by Severity
Number and severity of TEAEs were evaluated. The severity grades of AEs were defined as: mild, moderate, and severe. Note: the numbers listed do not include the TEAEs with missing severity.
Time frame: From the start of the study up to 1 month follow-up
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Caplacizumab | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Mild | 348 adverse events |
| Caplacizumab | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Moderate | 154 adverse events |
| Caplacizumab | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Severe | 37 adverse events |
| Placebo | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Mild | 299 adverse events |
| Placebo | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Moderate | 173 adverse events |
| Placebo | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Severe | 23 adverse events |
Secondary
PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time
The change from baseline in FVIII:C concentration was measured at different ime points.
Time frame: From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 1 of daily PE, post dose | 104 Percentage of FVIII:C activity | Standard Deviation 6.95 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 2 after daily PE | 125.2 Percentage of FVIII:C activity | Standard Deviation 16.88 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Last day of daily PE, post dose | 102.4 Percentage of FVIII:C activity | Standard Deviation 10.91 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 3 after daily PE | 106.3 Percentage of FVIII:C activity | Standard Deviation 9.7 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Baseline | 144.18 Percentage of FVIII:C activity | Standard Deviation 11.14 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 4 after daily PE | 95.8 Percentage of FVIII:C activity | Standard Deviation 6.09 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 1 after daily PE | 116.3 Percentage of FVIII:C activity | Standard Deviation 13.33 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 3 of follow-up period | 146.3 Percentage of FVIII:C activity | Standard Deviation 12.59 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 2 of daily PE, post dose | 90.7 Percentage of FVIII:C activity | Standard Deviation 5.49 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 7 of follow-up period | 208.6 Percentage of FVIII:C activity | Standard Deviation 15.54 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 1 after daily PE | 116.4 Percentage of FVIII:C activity | Standard Deviation 11.73 |
| Caplacizumab | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | 1 month follow-up | 212.2 Percentage of FVIII:C activity | Standard Deviation 17.33 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | 1 month follow-up | 200.1 Percentage of FVIII:C activity | Standard Deviation 17.11 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Baseline | 156.8 Percentage of FVIII:C activity | Standard Deviation 12.54 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 1 of daily PE, post dose | 149 Percentage of FVIII:C activity | Standard Deviation 9.16 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 2 of daily PE, post dose | 152.9 Percentage of FVIII:C activity | Standard Deviation 9.41 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Last day of daily PE, post dose | 169.5 Percentage of FVIII:C activity | Standard Deviation 17.79 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 1 after daily PE | 234.2 Percentage of FVIII:C activity | Standard Deviation 16.05 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 1 after daily PE | 296.8 Percentage of FVIII:C activity | Standard Deviation 26.07 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 2 after daily PE | 291.1 Percentage of FVIII:C activity | Standard Deviation 18.25 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 3 after daily PE | 273.1 Percentage of FVIII:C activity | Standard Deviation 20.35 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Week 4 after daily PE | 249.1 Percentage of FVIII:C activity | Standard Deviation 18.27 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 3 of follow-up period | 227.7 Percentage of FVIII:C activity | Standard Deviation 17.32 |
| Placebo | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | Day 7 of follow-up period | 237.5 Percentage of FVIII:C activity | Standard Deviation 15.65 |
Secondary
Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time
The change from baseline in RICO activity was measured at different time points.
Time frame: From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Baseline | 76.2 percentage of RICO activity | Standard Deviation 4.95 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 1 of daily PE, post dose | 16.2 percentage of RICO activity | Standard Deviation 0.72 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 2 of daily PE, post dose | 21.4 percentage of RICO activity | Standard Deviation 3.64 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Last day of daily PE, post dose | 15.4 percentage of RICO activity | Standard Deviation 0.39 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 1 after daily PE | 19.2 percentage of RICO activity | Standard Deviation 3.94 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 1 after daily PE | 15 percentage of RICO activity | Standard Deviation 0 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 2 after daily PE | 18.9 percentage of RICO activity | Standard Deviation 2.87 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 3 after daily PE | 17.4 percentage of RICO activity | Standard Deviation 2.34 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 4 after daily PE | 15.1 percentage of RICO activity | Standard Deviation 0.07 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 3 of follow-up period | 42.3 percentage of RICO activity | Standard Deviation 6.33 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 7 of follow-up period | 88.3 percentage of RICO activity | Standard Deviation 4.99 |
| Caplacizumab | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | 1 month follow-up | 94.6 percentage of RICO activity | Standard Deviation 3.78 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 7 of follow-up period | 99.7 percentage of RICO activity | Standard Deviation 4.06 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Baseline | 82.1 percentage of RICO activity | Standard Deviation 3.76 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 2 after daily PE | 109.2 percentage of RICO activity | Standard Deviation 2.8 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 1 of daily PE, post dose | 84.4 percentage of RICO activity | Standard Deviation 6.09 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 3 of follow-up period | 99.1 percentage of RICO activity | Standard Deviation 4.56 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 2 of daily PE, post dose | 94.4 percentage of RICO activity | Standard Deviation 3.69 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 3 after daily PE | 104 percentage of RICO activity | Standard Deviation 3.46 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Last day of daily PE, post dose | 118.2 percentage of RICO activity | Standard Deviation 1.78 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | 1 month follow-up | 94.7 percentage of RICO activity | Standard Deviation 5.35 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Day 1 after daily PE | 105.2 percentage of RICO activity | Standard Deviation 4.31 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 4 after daily PE | 105.5 percentage of RICO activity | Standard Deviation 3.59 |
| Placebo | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | Week 1 after daily PE | 107.3 percentage of RICO activity | Standard Deviation 3.05 |
Secondary
Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time
The change from baseline in vWF:Ag concentration was measured at different time points.
Time frame: From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Baseline | 185.1 Percentage of vWF:Ag | Standard Deviation 15.09 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 1 of daily PE, post dose | 120.6 Percentage of vWF:Ag | Standard Deviation 7.98 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 2 of daily PE, post dose | 94.6 Percentage of vWF:Ag | Standard Deviation 4.83 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Last day of daily PE, post dose | 93.6 Percentage of vWF:Ag | Standard Deviation 6.01 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 1 after daily PE | 86.2 Percentage of vWF:Ag | Standard Deviation 6.15 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 1 after daily PE | 93.4 Percentage of vWF:Ag | Standard Deviation 6.4 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 2 after daily PE | 115.9 Percentage of vWF:Ag | Standard Deviation 12.42 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 3 after daily PE | 102.4 Percentage of vWF:Ag | Standard Deviation 6.45 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 4 after daily PE | 100.1 Percentage of vWF:Ag | Standard Deviation 5 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 3 of follow-up period | 137.8 Percentage of vWF:Ag | Standard Deviation 9.32 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 7 of follow-up period | 190.2 Percentage of vWF:Ag | Standard Deviation 12.9 |
| Caplacizumab | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | 1 month follow-up | 176.3 Percentage of vWF:Ag | Standard Deviation 15.63 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 7 of follow-up period | 190.3 Percentage of vWF:Ag | Standard Deviation 14.81 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Baseline | 204.4 Percentage of vWF:Ag | Standard Deviation 14.52 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 2 after daily PE | 242.6 Percentage of vWF:Ag | Standard Deviation 19.43 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 1 of daily PE, post dose | 166.6 Percentage of vWF:Ag | Standard Deviation 9.24 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 3 of follow-up period | 184.1 Percentage of vWF:Ag | Standard Deviation 13.89 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 2 of daily PE, post dose | 140.2 Percentage of vWF:Ag | Standard Deviation 6.16 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 3 after daily PE | 224.2 Percentage of vWF:Ag | Standard Deviation 18.62 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Last day of daily PE, post dose | 151.2 Percentage of vWF:Ag | Standard Deviation 14.25 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | 1 month follow-up | 167.2 Percentage of vWF:Ag | Standard Deviation 15.46 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Day 1 after daily PE | 166 Percentage of vWF:Ag | Standard Deviation 10.05 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 4 after daily PE | 204.3 Percentage of vWF:Ag | Standard Deviation 17.08 |
| Placebo | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | Week 1 after daily PE | 234.9 Percentage of vWF:Ag | Standard Deviation 20.91 |
Secondary
Plasma Concentrations of Caplacizumab
The concentration of caplacizumab in plasma was determined at different time points. pharmacokinetics (PK) Population: the PK Population consisted of all subjects who received the study drug and for whom the primary PK data are considered to be sufficient and interpretable.
Time frame: From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Population: PK Population, no PK data were generated for the subjects in the placebo group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 2 of daily PE, predose | 288 ng/mL | Standard Error 24.05 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Baseline | 100 ng/mL | Standard Error 0 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 1 of daily PE, 5 - 10 min postdose | 1765.9 ng/mL | Standard Error 185.04 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 1 of daily PE, 3 - 6 hours postdose | 450.4 ng/mL | Standard Error 36.15 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 1 of daily PE, 8 - 24 hours postdose | 562 ng/mL | Standard Error 36.8 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 2 of daily PE, 1 - 6 hours postdose | 415.8 ng/mL | Standard Error 24.75 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 2 of daily PE, 6 - 12 hours postdose | 570.7 ng/mL | Standard Error 52.22 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 2 of daily PE, 18 - 24 hours postdose | 489.3 ng/mL | Standard Error 32.54 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Last day of daily PE, predose | 348.4 ng/mL | Standard Error 38.32 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 1 after daily PE | 521.9 ng/mL | Standard Error 31.52 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Week 1 after daily PE | 490.6 ng/mL | Standard Error 36.11 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Week 2 after daily PE | 524.9 ng/mL | Standard Error 39.37 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Week 3 after daily PE | 499.6 ng/mL | Standard Error 35.1 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Week 4 after daily PE | 503.4 ng/mL | Standard Error 31.21 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 3 of follow-up period | 346.7 ng/mL | Standard Error 25.43 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | Day 7 of follow-up period | 162.3 ng/mL | Standard Error 20.2 |
| Caplacizumab | Plasma Concentrations of Caplacizumab | 1 month follow-up | 100 ng/mL | Standard Error 0 |
Secondary
Resolution of Non-focal Neurological Symptoms
Resolution of non-focal neurological symptoms as defined by neurocognitive function at complete remission, measured by a Computerised Neuropsychological Test Battery(CNTB) (adults only). The CNTB included 6 modules: word list learning and selective reminding (WLL/SR), choice reaction time (CRT), visual memory (VMEM), simple reaction time (SRT), working memory (WMEM), and word list learning and delayed recall (WLL/DR). The 6 tasks are rated as a percentage correct (for CRT and SRT, the percentage correct corresponds to the percentage hits) and the mean score from these provides the CNTB summary score (range: 0-100). A higher CNTB summary score indicates better neuropsychological functioning.
Time frame: From Baseline till the 12-month FU visit
Population: The Computerized Neuropsychological Test Battery (CNTB) was completed by a low proportion of subjects with baseline data available for only 3 subjects in the caplacizumab and 4 subjects in the placebo group and 12 month post-discharge data available for 10 and 6 subjects, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caplacizumab | Resolution of Non-focal Neurological Symptoms | Baseline | 66.76 score on a scale | Standard Deviation 11.88 |
| Caplacizumab | Resolution of Non-focal Neurological Symptoms | 12 months post discharge | 62.10 score on a scale | Standard Deviation 12.06 |
| Placebo | Resolution of Non-focal Neurological Symptoms | Baseline | 49.62 score on a scale | Standard Deviation 12.91 |
| Placebo | Resolution of Non-focal Neurological Symptoms | 12 months post discharge | 58.36 score on a scale | Standard Deviation 10.23 |
Secondary
The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period
The maximum number of consecutive days per subject where there was no interruption of PE during the initial daily PE period.
Time frame: During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Population: Number of subjects from the ITT Population with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Caplacizumab | The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period | 6.6 days | Standard Deviation 3.35 |
| Placebo | The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period | 8.1 days | Standard Deviation 6.46 |
Secondary
Total Volume of Plasma Administered During the Initial Daily PE Period
The total volume of plasma administered during the initial daily PE period was measured.
Time frame: During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Population: Number of subjects from the ITT Population with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Caplacizumab | Total Volume of Plasma Administered During the Initial Daily PE Period | 22481.8 mL | Standard Deviation 15914.85 |
| Placebo | Total Volume of Plasma Administered During the Initial Daily PE Period | 28358.4 mL | Standard Deviation 21344.16 |