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

NCT06291025 | Recruiting

• 1 other identifier: 2021/0374/HP
• Study Type: interventional
• Target: 131
• Locations: 3 countries
• Sites: 30

Brief Summary

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.

Conditions

Thrombotic Microangiopathies

Outcome Measures

Primary Outcomes (1)

• 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%.

  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

Study Arms (1)

PEX-FREE

EXPERIMENTAL

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

Interventions

PEX-FREE PROCEDURE

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).

Also known as: PEX-FREE procedure

PEX-FREE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient ≥ 18 years;
• 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);

You may not qualify if:

• 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);

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (30)

Chu Amiens

Amiens, 80054, France

RECRUITING

Chu Angers

Angers, 49933, France

RECRUITING

Chru Besanon

Besançon, 25030, France

RECRUITING

Chu Bobigny

Bobigny, 93000, France

RECRUITING

Hopital Jean Verdie

Bondy, 93140, France

RECRUITING

Chu Bordeaux

Bordeaux, 33076, France

RECRUITING

Chu Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

Chu Lille

Lille, 59037, France

RECRUITING

Chu Limoges

Limoges, 87042, France

NOT YET RECRUITING

Chu Edouard Herriot

Lyon, 69003, France

RECRUITING

Ap-Hm La Conception

Marseille, 13005, France

RECRUITING

Chu Montpellier

Montpellier, 34295, France

RECRUITING

Chu Nancy

Nancy, 54500, France

RECRUITING

Chu Nantes

Nantes, 44093, France

RECRUITING

CHU NICE

Nice, 06200, France

RECRUITING

Chu Nimes

Nîmes, 30029, France

RECRUITING

Ap-Hp Saint Louis

Paris, 75010, France

RECRUITING

Ap-Hp St Antoine

Paris, 75571, France

RECRUITING

Ap-Hp Pitie Salpetriere

Paris, 75651, France

NOT YET RECRUITING

CH PAU

Pau, 64046, France

NOT YET RECRUITING

Chu Reims

Reims, 51092, France

RECRUITING

Chu Rouen

Rouen, 76031, France

RECRUITING

Ch Saint-Nazaire

Saint-Nazaire, 44606, France

NOT YET RECRUITING

Chu Strasbourg

Strasbourg, 67091, France

RECRUITING

Chu Toulouse

Toulouse, 31000, France

RECRUITING

Chu Tours

Tours, 37044, France

NOT YET RECRUITING

Ch Valenciennes

Valenciennes, 59322, France

RECRUITING

Chu Martinique

Fort-de-France, 97261, Martinique

NOT YET RECRUITING

Reunion Nord

Saint-Denis, 97400, Reunion

RECRUITING

Chu Reunion Sud

Saint-Pierre, 97448, Reunion

RECRUITING

MeSH Terms

Conditions

Thrombotic Microangiopathies

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Central Study Contacts

Ygal Benhamou, Pr

CONTACT

02 32 88 90 03; ygal.benhamou@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial is prospective, non-comparative, non-inferiority, single-arm, multicentric, national.

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: April 10, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (27); MA (1); RE (2)