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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04074187
Recruitment Status : Recruiting
First Posted : August 29, 2019
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Thrombotic Thrombocytopenic Purpura Drug: Caplacizumab (ALX-0081) Drug: Plasma exchange (PE) Drug: Corticosteroid treatment (Methylprednisolone or prednisolone) Drug: Immunosuppressive treatment (eg, rituximab) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Multicenter Trial to Study the Efficacy and Safety of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura
Actual Study Start Date : October 21, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. Time to stop of daily plasma exchnage (PE) [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Time to stop of daily PE

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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)

  15. Pharmacokineticks: plasma concentration [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Total caplacizumab plasma concentrations

  16. Immunogenicity of caplacizumab [ Time Frame: Approximately 2 months up to approximately 6 months ]
    Anti-drug antibodies



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04074187


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Japan
Investigational Site Number 3920008 Recruiting
Akita-Shi, Japan
Investigational Site Number 3920009 Recruiting
Iruma-Gun, Japan
Investigational Site Number 3920014 Recruiting
Kanazawa-Shi, Japan
Investigational Site Number 3920007 Recruiting
Kashihara-Shi, Japan
Investigational Site Number 3920013 Recruiting
Kawasaki-Shi, Japan
Investigational Site Number 3920001 Recruiting
Kitakyushu-Shi, Japan
Investigational Site Number 3920002 Recruiting
Kumamoto-Shi, Japan
Investigational Site Number 3920003 Recruiting
Kurashiki-Shi, Japan
Investigational Site Number 3920010 Recruiting
Kyoto-Shi, Japan
Investigational Site Number 3920005 Recruiting
Maebashi-Shi, Japan
Investigational Site Number 3920015 Recruiting
Nagoya, Japan
Investigational Site Number 3920011 Recruiting
Osaka-Shi, Japan
Investigational Site Number 3920004 Recruiting
Sapporo-Shi, Japan
Investigational Site Number 3920006 Recruiting
Sendai-Shi, Japan
Investigational Site Number 3920012 Recruiting
Wakayama-Shi, Japan
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04074187    
Other Study ID Numbers: EFC16297
U1111-1223-4914 ( Other Identifier: UTN )
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
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/

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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
Additional relevant MeSH terms:
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Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Rituximab
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Antiemetics