A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Study Details
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:
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To evaluate effect of caplacizumab on
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prevention of recurrence of TTP (the number of recurrences of TTP) during overall study period.
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a composite endpoint consisting of aTTP-related mortality, recurrence of aTTP and major thromboembolic events during study drug treatment
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restoring platelet counts as a measure of prevention of further microvascular thrombosis
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refractory disease
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biomarkers of organ damage: LDH, cardiac troponin I, serum creatinine
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plasma exchange (PE) parameters (days of PE and volume of plasma used), days in intensive care unit, days in hospital
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cognitive status of Japanese patients
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To evaluate safety profile of caplacizumab in Japanese patients
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To evaluate effect of caplacizumab on pharmacodynamic (PD) markers in Japanese patients
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To evaluate pharmacokinetic (PK) profile of caplacizumab in Japanese patients
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To evaluate immunogenicity of caplacizumab in Japanese patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Caplacizumab 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) |
Drug: Caplacizumab (ALX-0081)
Pharmaceutical form:Lyophilized powder for solution for injection Route of administration: IV (first dose), SC (all subsequent doses)
Drug: Plasma exchange (PE)
Pharmaceutical form:Plasma (e.g. fresh frozen plasma) Route of administration: Plasma exchange
Drug: Corticosteroid treatment (Methylprednisolone or prednisolone)
Pharmaceutical form:Solution for injection or Tablet Route of administration: IV or Oral
Drug: Immunosuppressive treatment (eg, rituximab)
Pharmaceutical form:Solution for injection (depending on product) Route of administration: IV (depending on product)
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- 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.
- 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).
- 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.
- 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.
- Time to stop of daily plasma exchnage (PE) [Approximately 2 months up to approximately 6 months]
Time to stop of daily PE
- 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
- 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.
- 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.
- 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
- 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)
- Pharmacokineticks: plasma concentration [Approximately 2 months up to approximately 6 months]
Total caplacizumab plasma concentrations
- Immunogenicity of caplacizumab [Approximately 2 months up to approximately 6 months]
Anti-drug antibodies
Eligibility Criteria
Criteria
Inclusion criteria :
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Japanese participant must be 18 years or older at the time of signing the informed consent.
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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
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Participants who require initiation of daily PE treatment and have received a maximum of 1 PE treatment prior to enrollment in the study
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Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
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Capable of giving signed informed consent
Exclusion criteria:
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Platelet count ≥100,000/µL,
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Serum creatinine level > 2.3mg/dL in case platelet count is > 30,000µL
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Known other causes of thrombocytopenia
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Congenital TTP
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Clinically significant active bleeding or high risk of bleeding
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Malignant arterial hypertension
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Known chronic treatment with anticoagulant treatment that cannot be stopped
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Participants who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
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Participants currently or less than 28 days prior to enrollment in this study, enrolled in a clinical study with another investigational drug or device
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Clinical condition other than that associated with TTP, with life expectancy < 6 months, such as end-stage malignancy
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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
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 3920009 | Iruma-Gun | Japan | ||
| 2 | Investigational Site Number 3920014 | Kanazawa-Shi | Japan | ||
| 3 | Investigational Site Number 3920007 | Kashihara-Shi | Japan | ||
| 4 | Investigational Site Number 3920013 | Kawasaki-Shi | Japan | ||
| 5 | Investigational Site Number 3920001 | Kitakyushu-Shi | Japan | ||
| 6 | Investigational Site Number 3920002 | Kumamoto-Shi | Japan | ||
| 7 | Investigational Site Number 3920003 | Kurashiki-Shi | Japan | ||
| 8 | Investigational Site Number 3920010 | Kyoto-Shi | Japan | ||
| 9 | Investigational Site Number 3920005 | Maebashi-Shi | Japan | ||
| 10 | Investigational Site Number 3920015 | Nagoya | Japan | ||
| 11 | Investigational Site Number 3920011 | Osaka-Shi | Japan | ||
| 12 | Investigational Site Number 3920006 | Sendai-Shi | Japan |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EFC16297
- U1111-1223-4914