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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

131

Phase

  • 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 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 Salpetrière
        • 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

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
Intervention / Treatment
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

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

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)

April 10, 2024

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

March 1, 2024

First Posted (Actual)

March 4, 2024

Study Record Updates

Last Update Posted (Actual)

February 17, 2026

Last Update Submitted That Met QC Criteria

February 13, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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