A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Interventions
- Drug: Plasma exchange (PE)Drug: Corticosteroid treatment (Methylprednisolone or prednisolone)Drug: Immunosuppressive treatment (eg, rituximab)
- Registration Number
- NCT04074187
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Caplacizumab Corticosteroid treatment (Methylprednisolone or prednisolone) 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) Caplacizumab Plasma exchange (PE) 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) Caplacizumab Caplacizumab (ALX-0081) 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) Caplacizumab Immunosuppressive treatment (eg, rituximab) 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)
- Primary Outcome Measures
Name Time Method Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP) Approximately 2 months up to approximately 6 months 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
Name Time Method Proportion of participant who have a platelet count ≥150,000/μL Approximately 2 months up to approximately 6 months 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).
Number of recurrences of TTP Approximately 2 months up to approximately 6 months 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 Approximately 2 months up to approximately 6 months 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).
Number of days to plasma exchange Approximately 2 months up to approximately 6 months 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 to platelet count response Approximately 2 months up to approximately 6 months 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 to stop of daily plasma exchnage (PE) Approximately 2 months up to approximately 6 months Time to stop of daily PE
Change from baseline in the standardized mini mental state exam (SMMSE) total score Approximately 2 months up to approximately 6 months 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.
Pharmacodynamic (PD) markers Approximately 2 months up to approximately 6 months PD parameters: von Willebrand factor antigen(vWF:Ag), coagulation factor VIII clotting activity (FVIII:C), von Willebrand factor ristocetin cofactor activity (vWF:RICO)
Immunogenicity of caplacizumab Approximately 2 months up to approximately 6 months Anti-drug antibodies
Proportion of participants with refractory TTP Approximately 2 months up to approximately 6 months 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.
Pharmacokineticks: plasma concentration Approximately 2 months up to approximately 6 months Total caplacizumab plasma concentrations
Time to normalization of 3 organ damage marker levels Approximately 2 months up to approximately 6 months 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.
Total volume of plasma Approximately 2 months up to approximately 6 months 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 Approximately 2 months up to approximately 6 months 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.
Proportion of participants with at least one treatment emergent thromboembolic event Approximately 2 months up to approximately 6 months 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 Approximately 2 months up to approximately 6 months Number of Patients with treatment emergent Adverse events (AEs) and serious adverse events (SAEs) and bleeding events
Trial Locations
- Locations (12)
Investigational Site Number 3920009
🇯🇵Iruma-Gun, Japan
Investigational Site Number 3920007
🇯🇵Kashihara-Shi, Japan
Investigational Site Number 3920003
🇯🇵Kurashiki-Shi, Japan
Investigational Site Number 3920005
🇯🇵Maebashi-Shi, Japan
Investigational Site Number 3920015
🇯🇵Nagoya, Japan
Investigational Site Number 3920010
🇯🇵Kyoto-Shi, Japan
Investigational Site Number 3920011
🇯🇵Osaka-Shi, Japan
Investigational Site Number 3920006
🇯🇵Sendai-Shi, Japan
Investigational Site Number 3920014
🇯🇵Kanazawa-Shi, Japan
Investigational Site Number 3920013
🇯🇵Kawasaki-Shi, Japan
Investigational Site Number 3920001
🇯🇵Kitakyushu-Shi, Japan
Investigational Site Number 3920002
🇯🇵Kumamoto-Shi, Japan