A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Primary Purpose
Thrombotic Thrombocytopenic Purpura
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Caplacizumab (ALX-0081)
Plasma exchange (PE)
Corticosteroid treatment (Methylprednisolone or prednisolone)
Immunosuppressive treatment (eg, rituximab)
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura
Eligibility Criteria
Inclusion criteria :
- Japanese participant must be 18 years or older at the time of signing the informed consent.
- Participants who have a clinical diagnosis of aTTP (initial or recurrent), which includes thrombocytopenia (defined as platelet count <100,000/µL), microangiopathic hemolytic anemia as evidenced by red blood cell fragmentation (eg, presence of schistocytes), and increased levels of LDH
- Participants who require initiation of daily PE treatment and have received a maximum of 1 PE treatment prior to enrollment in the study
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- Capable of giving signed informed consent
Exclusion criteria:
- Platelet count ≥100,000/µL,
- Serum creatinine level > 2.3mg/dL in case platelet count is > 30,000µL
- Known other causes of thrombocytopenia
- Congenital TTP
- Clinically significant active bleeding or high risk of bleeding
- Malignant arterial hypertension
- Known chronic treatment with anticoagulant treatment that cannot be stopped
- Participants who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
- Participants currently or less than 28 days prior to enrollment in this study, enrolled in a clinical study with another investigational drug or device
- Clinical condition other than that associated with TTP, with life expectancy < 6 months, such as end-stage malignancy
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
- Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 3920009
- Investigational Site Number 3920014
- Investigational Site Number 3920007
- Investigational Site Number 3920013
- Investigational Site Number 3920001
- Investigational Site Number 3920002
- Investigational Site Number 3920003
- Investigational Site Number 3920010
- Investigational Site Number 3920005
- Investigational Site Number 3920015
- Investigational Site Number 3920011
- Investigational Site Number 3920006
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Caplacizumab
Arm Description
Eligible study participants will receive caplacizumab in addition to standard of care such as daily plasma exchange (PE) and corticosteroid treatment (mandatory), immunosuppressive treatment (if needed)
Outcomes
Primary Outcome Measures
Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP)
Proportion of participants with a recurrence of aTTP during the overall study period. The success criterion for this study is proportion of evaluable participants (per-protocol population) with a recurrence of aTTP during the overall study period to be 20% or less.
Secondary Outcome Measures
Number of recurrences of TTP
Number of recurrences of TTP during study drug treatment (including extensions) and follow-up, as well as during overall study period.
Proportion of participants with composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events
Proportion of participants with TTP-related death, a recurrence of TTP, or at least one treatmentemergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions).
Time to platelet count response
Time to platelet count response, defined as initial platelet count ≥150,000/μL with subsequent stop of daily plasma exchange (PE) within 5 days.
Proportion of participant who have a platelet count ≥150,000/μL
Proportion of participant who have a platelet count ≥150,000/μL on Day 1, 2, 3, 4, 5 and Day 10 and end of study drug treatment (ie, last weekly visit during the overall treatment period).
Proportion of participants with refractory TTP
Proportion of participant with refractory TTP, defined as persistent thrombocytopenia, lack of sustained platelet count increment or platelet counts <50,000/μL and persistently elevated LDH (>1.5 x upper limit of normal [ULN]) despite 5 PEs and steroid treatment.
Time to normalization of 3 organ damage marker levels
Time to normalization of all 3 of the following organ damage marker levels: Time to LDH ≤ 1 x ULN, and cTnI ≤ 1 x ULN, and serum creatinine ≤ 1 x ULN and time to individual organ damage marker level.
Time to stop of daily plasma exchnage (PE)
Time to stop of daily PE
Number of days to plasma exchange
The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period
Total volume of plasma
The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period
Number of days in ICU and in hospital
Number of days in ICU and in hospital in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, in the Follow-up period (of 4 weeks after stop of study drug treatment) and overall study period.
Change from baseline in the standardized mini mental state exam (SMMSE) total score
Change from baseline in SMMSE total score on Day 1, (Day 2, 3, 4 as optional) and Day 5 of daily Plasma Exchange (PE) period, and Weeks 1 and 5 of the 30-day postdaily PE period, and the first (7 days after last dosing) and final follow-up (28 days after last dosing) visit.
Proportion of participants with at least one treatment emergent thromboembolic event
The treatment-emergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions) will be evaluated.
Number of patients with treatment emergent adverse events
Number of Patients with treatment emergent Adverse events (AEs) and serious adverse events (SAEs) and bleeding events
Pharmacodynamic (PD) markers
PD parameters: von Willebrand factor antigen(vWF:Ag), coagulation factor VIII clotting activity (FVIII:C), von Willebrand factor ristocetin cofactor activity (vWF:RICO)
Pharmacokineticks: plasma concentration
Total caplacizumab plasma concentrations
Immunogenicity of caplacizumab
Anti-drug antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04074187
Brief Title
A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Official Title
An Open-label Multicenter Trial to Study the Efficacy and Safety of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 21, 2019 (Actual)
Primary Completion Date
May 19, 2021 (Actual)
Study Completion Date
May 19, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary Objective:
To evaluate the effect of caplacizumab on prevention of recurrence of aTTP (proportion of participants with a recurrence of aTTP) during the overall study period.
Secondary Objectives:
To evaluate effect of caplacizumab on
prevention of recurrence of TTP (the number of recurrences of TTP) during overall study period.
a composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events during study drug treatment
restoring platelet counts as a measure of prevention of further microvascular thrombosis
refractory disease
biomarkers of organ damage: LDH, cardiac troponin I, serum creatinine
plasma exchange (PE) parameters (days of PE and volume of plasma used), days in intensive care unit, days in hospital
cognitive status of Japanese patients
To evaluate safety profile of caplacizumab in Japanese patients
To evaluate effect of caplacizumab on pharmacodynamic (PD) markers in Japanese patients
To evaluate pharmacokinetic (PK) profile of caplacizumab in Japanese patients
To evaluate immunogenicity of caplacizumab in Japanese patients
Detailed Description
Study duration per participant is approximately 2 months up to approximately 6 months in case of treatment extension and recurrence during the study drug treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Caplacizumab
Arm Type
Experimental
Arm Description
Eligible study participants will receive caplacizumab in addition to standard of care such as daily plasma exchange (PE) and corticosteroid treatment (mandatory), immunosuppressive treatment (if needed)
Intervention Type
Drug
Intervention Name(s)
Caplacizumab (ALX-0081)
Intervention Description
Pharmaceutical form:Lyophilized powder for solution for injection Route of administration: IV (first dose), SC (all subsequent doses)
Intervention Type
Drug
Intervention Name(s)
Plasma exchange (PE)
Intervention Description
Pharmaceutical form:Plasma (e.g. fresh frozen plasma) Route of administration: Plasma exchange
Intervention Type
Drug
Intervention Name(s)
Corticosteroid treatment (Methylprednisolone or prednisolone)
Intervention Description
Pharmaceutical form:Solution for injection or Tablet Route of administration: IV or Oral
Intervention Type
Drug
Intervention Name(s)
Immunosuppressive treatment (eg, rituximab)
Intervention Description
Pharmaceutical form:Solution for injection (depending on product) Route of administration: IV (depending on product)
Primary Outcome Measure Information:
Title
Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP)
Description
Proportion of participants with a recurrence of aTTP during the overall study period. The success criterion for this study is proportion of evaluable participants (per-protocol population) with a recurrence of aTTP during the overall study period to be 20% or less.
Time Frame
Approximately 2 months up to approximately 6 months
Secondary Outcome Measure Information:
Title
Number of recurrences of TTP
Description
Number of recurrences of TTP during study drug treatment (including extensions) and follow-up, as well as during overall study period.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Proportion of participants with composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events
Description
Proportion of participants with TTP-related death, a recurrence of TTP, or at least one treatmentemergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions).
Time Frame
Approximately 2 months up to approximately 6 months
Title
Time to platelet count response
Description
Time to platelet count response, defined as initial platelet count ≥150,000/μL with subsequent stop of daily plasma exchange (PE) within 5 days.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Proportion of participant who have a platelet count ≥150,000/μL
Description
Proportion of participant who have a platelet count ≥150,000/μL on Day 1, 2, 3, 4, 5 and Day 10 and end of study drug treatment (ie, last weekly visit during the overall treatment period).
Time Frame
Approximately 2 months up to approximately 6 months
Title
Proportion of participants with refractory TTP
Description
Proportion of participant with refractory TTP, defined as persistent thrombocytopenia, lack of sustained platelet count increment or platelet counts <50,000/μL and persistently elevated LDH (>1.5 x upper limit of normal [ULN]) despite 5 PEs and steroid treatment.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Time to normalization of 3 organ damage marker levels
Description
Time to normalization of all 3 of the following organ damage marker levels: Time to LDH ≤ 1 x ULN, and cTnI ≤ 1 x ULN, and serum creatinine ≤ 1 x ULN and time to individual organ damage marker level.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Time to stop of daily plasma exchnage (PE)
Description
Time to stop of daily PE
Time Frame
Approximately 2 months up to approximately 6 months
Title
Number of days to plasma exchange
Description
The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period
Time Frame
Approximately 2 months up to approximately 6 months
Title
Total volume of plasma
Description
The endpoint will be assessed in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, follow-up period (of 4 weeks after stop of study drug treatment), and overall study period
Time Frame
Approximately 2 months up to approximately 6 months
Title
Number of days in ICU and in hospital
Description
Number of days in ICU and in hospital in 4 time periods: daily PE period (the first daily PE period only), overall treatment period, in the Follow-up period (of 4 weeks after stop of study drug treatment) and overall study period.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Change from baseline in the standardized mini mental state exam (SMMSE) total score
Description
Change from baseline in SMMSE total score on Day 1, (Day 2, 3, 4 as optional) and Day 5 of daily Plasma Exchange (PE) period, and Weeks 1 and 5 of the 30-day postdaily PE period, and the first (7 days after last dosing) and final follow-up (28 days after last dosing) visit.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Proportion of participants with at least one treatment emergent thromboembolic event
Description
The treatment-emergent major thromboembolic event (eg, myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis [DVT]) during the overall treatment period (including extensions) will be evaluated.
Time Frame
Approximately 2 months up to approximately 6 months
Title
Number of patients with treatment emergent adverse events
Description
Number of Patients with treatment emergent Adverse events (AEs) and serious adverse events (SAEs) and bleeding events
Time Frame
Approximately 2 months up to approximately 6 months
Title
Pharmacodynamic (PD) markers
Description
PD parameters: von Willebrand factor antigen(vWF:Ag), coagulation factor VIII clotting activity (FVIII:C), von Willebrand factor ristocetin cofactor activity (vWF:RICO)
Time Frame
Approximately 2 months up to approximately 6 months
Title
Pharmacokineticks: plasma concentration
Description
Total caplacizumab plasma concentrations
Time Frame
Approximately 2 months up to approximately 6 months
Title
Immunogenicity of caplacizumab
Description
Anti-drug antibodies
Time Frame
Approximately 2 months up to approximately 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria :
Japanese participant must be 18 years or older at the time of signing the informed consent.
Participants who have a clinical diagnosis of aTTP (initial or recurrent), which includes thrombocytopenia (defined as platelet count <100,000/µL), microangiopathic hemolytic anemia as evidenced by red blood cell fragmentation (eg, presence of schistocytes), and increased levels of LDH
Participants who require initiation of daily PE treatment and have received a maximum of 1 PE treatment prior to enrollment in the study
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Capable of giving signed informed consent
Exclusion criteria:
Platelet count ≥100,000/µL,
Serum creatinine level > 2.3mg/dL in case platelet count is > 30,000µL
Known other causes of thrombocytopenia
Congenital TTP
Clinically significant active bleeding or high risk of bleeding
Malignant arterial hypertension
Known chronic treatment with anticoagulant treatment that cannot be stopped
Participants who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
Participants currently or less than 28 days prior to enrollment in this study, enrolled in a clinical study with another investigational drug or device
Clinical condition other than that associated with TTP, with life expectancy < 6 months, such as end-stage malignancy
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 3920009
City
Iruma-Gun
Country
Japan
Facility Name
Investigational Site Number 3920014
City
Kanazawa-Shi
Country
Japan
Facility Name
Investigational Site Number 3920007
City
Kashihara-Shi
Country
Japan
Facility Name
Investigational Site Number 3920013
City
Kawasaki-Shi
Country
Japan
Facility Name
Investigational Site Number 3920001
City
Kitakyushu-Shi
Country
Japan
Facility Name
Investigational Site Number 3920002
City
Kumamoto-Shi
Country
Japan
Facility Name
Investigational Site Number 3920003
City
Kurashiki-Shi
Country
Japan
Facility Name
Investigational Site Number 3920010
City
Kyoto-Shi
Country
Japan
Facility Name
Investigational Site Number 3920005
City
Maebashi-Shi
Country
Japan
Facility Name
Investigational Site Number 3920015
City
Nagoya
Country
Japan
Facility Name
Investigational Site Number 3920011
City
Osaka-Shi
Country
Japan
Facility Name
Investigational Site Number 3920006
City
Sendai-Shi
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
36427162
Citation
Miyakawa Y, Imada K, Ichikawa S, Uchiyama H, Ueda Y, Yonezawa A, Fujitani S, Ogawa Y, Matsushita T, Asakura H, Nishio K, Suzuki K, Hashimoto Y, Murakami H, Tahara S, Tanaka T, Matsumoto M. The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study. Int J Hematol. 2023 Mar;117(3):366-377. doi: 10.1007/s12185-022-03495-6. Epub 2022 Nov 24.
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A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
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