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A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

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ClinicalTrials.gov Identifier: NCT04074187
Recruitment Status : Recruiting
First Posted : August 29, 2019
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE August 14, 2019
First Posted Date  ICMJE August 29, 2019
Last Update Posted Date November 26, 2019
Actual Study Start Date  ICMJE November 2, 2019
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2019)
Proportion of participants with a recurrence of acquired thrombotic thrombocytopenic purpura (aTTP) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2019)
  • Number of recurrences of TTP [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Time to stop of daily PE
  • Number of days to plasma exchange [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Total caplacizumab plasma concentrations
  • Immunogenicity of caplacizumab [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Anti-drug antibodies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Official Title  ICMJE An Open-label Multicenter Trial to Study the Efficacy and Safety of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Thrombotic Thrombocytopenic Purpura
Intervention  ICMJE
  • 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)
Study Arms  ICMJE 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)
Interventions:
  • Drug: Caplacizumab (ALX-0081)
  • Drug: Plasma exchange (PE)
  • Drug: Corticosteroid treatment (Methylprednisolone or prednisolone)
  • Drug: Immunosuppressive treatment (eg, rituximab)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 28, 2019)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04074187
Other Study ID Numbers  ICMJE EFC16297
U1111-1223-4914 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP