Efficacy and Safety of Immunosuppression, Caplacizumab and Plasma Infusion Without Therapeutic Plasma Exchange in Immune-mediated Thrombotic Thrombocytopenic Purpura (PEX-FREE)

February 13, 2026 updated by: University Hospital, Rouen

Efficacy and Safety of Immunosuppression, Caplacizumab and Plasma Infusion Without Therapeutic Plasma Exchange in Immune-mediated Thrombotic Thrombocytopenic Purpura: Multicentric Non-inferiority Single-arm Study

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a severe, autoantibody-mediated deficiency of ADAMTS13 leading to an accumulation of ultra-large von Willebrand factor multimers in plasma and finally to microthrombi in blood vessels. The current standard of care of iTTP consists in the triple association of daily plasma exchange (PEX, 60 ml/kg/day), immunosuppressive agents and anti-adhesive treatment (Caplacizumab). Our group recently reported the outcome of 90 patients with iTTP treated with this triple association and when compared to historical patients, the triplet regimen prevented death, refractoriness and exacerbations. Likewise, plasma volumes were reduced by 2 to 3-fold and the median number of PEX sessions could be reduced from 13 to 6. PEX is an invasive and time-consuming procedure, associated with catheter and plasma-related complications ranging from 22% to 30%. Consequently, to alleviate the burden of care in iTTP, using a regimen without PEX would represent a major and topical goal. Attempts to treat patients with plasma infusion (PI) without PEX were previously reported and provided evidence that large volumes of PI (20-30 ml/kg/day) improved the initial outcome of iTTP. However, fluid overload occurred in most cases after 5-7 days, limiting the feasibility of this strategy. Nevertheless, the recent availability of caplacizumab opens the perspective of treating patients with plasma for a shorter period. Recently, strategies without PEX have been carried out in Jehovah's Witnesses with iTTP [5]. Impressively, improvement was rapid and comparable to those provided with a standard PEX-based treatment. Additionally, a treatment combining caplacizumab and immunosuppression only was successfully performed in six iTTP patients with severe neurologic and/or cardiac involvement. The rapid and durable improvement provides evidence that a regimen without plasma seems feasible. However, it's considered that robust data are still lacking to completely remove plasmatherapy from iTTP management. Based on these statements, the objective is to address the efficacy and safety of a PEX-free regimen, combining PI only (15 ml/kg/day), corticosteroids/rituximab, and caplacizumab.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a severe, autoantibody-mediated deficiency of ADAMTS13 leading to an accumulation of ultra-large von Willebrand factor multimers in plasma and finally to microthrombi in blood vessels. The current standard of care of iTTP consists in the triple association of daily plasma exchange (PEX, 60 ml/kg/day), immunosuppressive agents and anti-adhesive treatment (Caplacizumab). Our group recently reported the outcome of 90 patients with iTTP treated with this triple association and when compared to historical patients, the triplet regimen prevented death, refractoriness and exacerbations. Likewise, plasma volumes were reduced by 2 to 3-fold and the median number of PEX sessions could be reduced from 13 to 6. PEX is an invasive and time-consuming procedure, associated with catheter and plasma-related complications ranging from 22% to 30%. Consequently, to alleviate the burden of care in iTTP, using a regimen without PEX would represent a major and topical goal. Attempts to treat patients with plasma infusion (PI) without PEX were previously reported and provided evidence that large volumes of PI (20-30 ml/kg/day) improved the initial outcome of iTTP. However, fluid overload occurred in most cases after 5-7 days, limiting the feasibility of this strategy. Nevertheless, the recent availability of caplacizumab opens the perspective of treating patients with plasma for a shorter period. Recently, strategies without PEX have been carried out in Jehovah's Witnesses with iTTP [5]. Impressively, improvement was rapid and comparable to those provided with a standard PEX-based treatment. Additionally, a treatment combining caplacizumab and immunosuppression only was successfully performed in six iTTP patients with severe neurologic and/or cardiac involvement. The rapid and durable improvement provides evidence that a regimen without plasma seems feasible. However, it's considered that robust data are still lacking to completely remove plasmatherapy from iTTP management. Based on these statements, the objective is to address the efficacy and safety of a PEX-free regimen, combining PI only (15 ml/kg/day), corticosteroids/rituximab, and caplacizumab.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
131

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Amiens, France, 80054
        • Recruiting
        • CHU Amiens
        • Contact:
        • Principal Investigator:
          • Coralie Poulain, Dr
      • Angers, France, 49933
        • Recruiting
        • CHU Angers
        • Contact:
        • Principal Investigator:
          • Jean-François Augusto, Dr
      • Besançon, France, 25030
        • Recruiting
        • Chru Besanon
        • Contact:
        • Principal Investigator:
          • Anne Rumpler, Dr
      • Bobigny, France, 93000
        • Recruiting
        • Chu Bobigny
        • Contact:
        • Principal Investigator:
          • Julien Schmidt, Dr
      • Bondy, France, 93140
        • Recruiting
        • Hopital Jean Verdie
        • Contact:
        • Principal Investigator:
          • Laurent Gilardin, Dr
      • Bordeaux, France, 33076
        • Recruiting
        • CHU Bordeaux
        • Contact:
        • Principal Investigator:
          • Yahsou Delmas, Dr
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • CHU Clermont-Ferrand
        • Contact:
        • Principal Investigator:
          • Virginie Rieu, Dr
      • Lille, France, 59037
        • Recruiting
        • CHU Lille
        • Contact:
        • Principal Investigator:
          • François Provot, Dr
      • Limoges, France, 87042
      • Lyon, France, 69003
        • Recruiting
        • Chu Edouard Herriot
        • Contact:
        • Principal Investigator:
          • Manon Marie, Dr
      • Marseille, France, 13005
        • Recruiting
        • Ap-Hm La Conception
        • Contact:
        • Principal Investigator:
          • Pascale Poullin, Dr
      • Montpellier, France, 34295
        • Recruiting
        • CHU Montpellier
        • Contact:
        • Principal Investigator:
          • Kada Klouche, Dr
      • Nancy, France, 54500
        • Recruiting
        • Chu Nancy
        • Contact:
        • Principal Investigator:
          • Pierre Perez, Dr
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes
        • Contact:
        • Principal Investigator:
          • Emmanuel Canet, Dr
        • Sub-Investigator:
          • Tanguy Le Scornet, Dr
        • Sub-Investigator:
          • Antoine Neel, Dr
      • Nice, France, 06200
        • Recruiting
        • CHU Nice
        • Contact:
        • Principal Investigator:
          • Lucas Morand, Dr
      • Nîmes, France, 30029
        • Recruiting
        • CHU Nimes
        • Contact:
        • Principal Investigator:
          • Olivier Moranne, Dr
      • Paris, France, 75010
        • Recruiting
        • Ap-Hp Saint Louis
        • Contact:
        • Principal Investigator:
          • Eric Mariotte, Dr
      • Paris, France, 75571
        • Recruiting
        • AP-HP St Antoine
        • Contact:
        • Principal Investigator:
          • Paul Coppo, Pr
      • Paris, France, 75651
        • Not yet recruiting
        • AP-HP Pitié Salpêtrière
        • Contact:
        • Principal Investigator:
          • Samir Saheb, Dr
      • Pau, France, 64046
        • Not yet recruiting
        • CH PAU
        • Contact:
        • Principal Investigator:
          • Laure Burguet, Dr
      • Reims, France, 51092
        • Recruiting
        • CHU Reims
        • Contact:
        • Principal Investigator:
          • Alain Wynckel, Dr
      • Rouen, France, 76031
        • Recruiting
        • CHU Rouen
        • Contact:
        • Principal Investigator:
          • Ygal Benhamou, Pr
      • Saint-Nazaire, France, 44606
        • Not yet recruiting
        • CH Saint-Nazaire
        • Contact:
        • Principal Investigator:
          • François Nazaire, Pr
      • Strasbourg, France, 67091
      • Toulouse, France, 31000
        • Recruiting
        • Chu Toulouse
        • Contact:
        • Principal Investigator:
          • Stanislas Faguer, Pr
      • Tours, France, 37044
        • Not yet recruiting
        • CHU Tours
        • Contact:
        • Principal Investigator:
          • Charlotte Salmon, Dr
      • Valenciennes, France, 59322
        • Recruiting
        • CH Valenciennes
        • Contact:
        • Principal Investigator:
          • Claire Cartery, Dr
  • Martinique
      • Fort-de-France, Martinique, 97261
        • Not yet recruiting
        • CHU Martinique
        • Contact:
        • Principal Investigator:
          • Christophe Deligny, Dr
  • Reunion
      • Saint-Denis, Reunion, 97400
        • Recruiting
        • Reunion Nord
        • Contact:
        • Principal Investigator:
          • Ludovic Di Ascia, Dr
      • Saint-Pierre, Reunion, 97448
        • Recruiting
        • Chu Reunion Sud
        • Contact:
        • Principal Investigator:
          • Patricia Zunic, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patient ≥ 18 years;
  • Clinical diagnosis of iTTP based on standard clinical and laboratory criteria (French Score ≥ 2): i.e., thrombotic microangiopathy syndrome with platelet count ≤ 30 G/L and serum creatinine ≤ 200 μmol/L; it is not necessary to have the laboratory result confirming the severe ADAMTS13 deficiency for inclusion of patient [32] (For patient with previous TTPflare, French score can be < 2);
  • Patient having read and understood the information letter and signed the Informed Consent Form. If the patient is unable to express his consent, the consent will be signed by his representative ((1) the trusted person, or failing that, (2) a family member, or (3) a close relative of the person concerned). In this case, consent to continue the study will subsequently be requested from the patient (article L1122-1-1 of the CSP);
  • Patient affiliated with, or beneficiary of a social security (national health insurance) plan;

  • For women:

    • Women of childbearing potential :

      • Effective contraception according to WHO definition (estrogen-progestin or intrauterine device or tubal ligation) since at least 1 month and;
      • Negative blood pregnancy test;
    • Women surgically sterile (absence of ovaries and/or uterus);
    • Postmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit).

Exclusion Criteria:

  • Platelet count > 100 G/L before plasma treatment;
  • Patients with a French score < 2 (a serum creatinine level > 200 μmol/L and/or with a platelet count > 30 G/L), in order to exclude possible cases of hemolytic uremic syndrome (except for patient with previous TTPflare, French score can be < 2);
  • Other known causes of cytopenias and/or organ failure including but not limited to: uncontrolled cancer, chemotherapy, transplant, drugs, HIV at AIDS stage;
  • Patients with a severe neurological disorder i.e. seizure, coma, focal deficiency, trouble of consciousness;
  • Pregnant women (positive result from a blood pregnancy test) or patients with an imminent project of pregnancy; breastfeeding women (due to lack of pharmacological data for caplacizumab during pregnancy and breastfeeding);
  • Weight > 100KG;
  • Congenital TTP;
  • Clinically significant active bleeding or high risk of bleeding (excluding thrombocytopenia);
  • Chronic treatment with anticoagulant that cannot be interrupted safely, including but not limited to: vitamin K antagonists, direct oral anticoagulant, low molecular weight heparin or heparin;
  • Malignant hypertension;
  • Contra-indication to CABLIVI 10 mg powder and solvent for solution for injection: hypersensitivity to caplacizumab or to any of the excipients;
  • Contra-indication to Plasma treatment;
  • Contra-indication to corticosteroid (= ((methyl)prednisone or (methyl)prednisolone)) or excipients;
  • Contra-indication to rituximab or excipients and to its premedication;
  • Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision);
  • Participation in another drug interventional clinical trial within 30 days prior to inclusion and during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PEX-FREE
Replacing daily PEX with daily plasma infusions (ie. Quarantine fresh frozen plasma (PFC-Se), solvent detergent/viral inactivated plasma (PFC-SD = OCTAPLASLG) or amotosalen-inactivated plasma (PFC-IA); volume 15mL/kg/day).
Procedure: PEX-FREE
The study/experimental procedure consists in replacing daily PEX with daily plasma infusions (ie. Quarantine fresh frozen plasma (PFC-Se), solvent detergent/viral inactivated plasma (PFC-SD = OCTAPLASLG) or amotosalen-inactivated plasma (PFC-IA); volume 15mL/kg/day).
Other Names:
  • PEX-FREE procedure

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of a PEX-FREE regimen in adults with iTTP as assessed by the proportion of participants day-30 post-plasma therapy death, refractoriness, exacerbation or an ADAMTS13 activity < 20%.
Time Frame: 30 days
Complete plasma infusion treatment and clinical remission at day 30 defined by both lack of occurrence of any of the four events during the 30 days post plasma infusion procedure
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Rouen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 10, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 26, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2021/0374/HP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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