Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (MAYARI)

An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura

This is a single group, treatment, Phase 3, open-label, single-arm study to evaluate the efficacy and safety of caplacizumab and immunosuppressive therapy (IST) without firstline therapeutic plasma exchange (TPE) with primary endpoint of remission in male and female participants aged 18 to 80 years with immune-mediated thrombotic thrombocytopenic purpura (iTTP).

The anticipated study duration per participant without a recurrence while on therapy is maximum 24 weeks (ie, approximately 1 day for screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up). Participants will have daily assessments during hospitalization and weekly visits for assessments during ongoing treatment with caplacizumab and IST. There will be 3 outpatient visits for assessments during the follow-up period. There will be two additional follow-up visits for participants who do not have ADAMTS13 activity levels of ≥50% at the time of caplacizumab discontinuation.

Study Overview

• Status: Completed
• Conditions: Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Caplacizumab; Drug: Corticosteroids; Biological: anti-CD20 antibody

Detailed Description

The anticipated study duration per participant with the presenting episode therefore is a maximum of about 24 weeks (ie, 1 day of screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up).

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Yvoir, Belgium, 5530
    • Investigational Site Number : 0560003
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Investigational Site Number : 1240001
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number : 2030001
  • Prague, Czechia, 128 00
    • Investigational Site Number : 2030003
• France
  • Bois-Guillaume, France, 76230
    • Investigational Site Number : 2500002
  • Lille, France, 59037
    • Investigational Site Number : 2500005
  • Paris, France, 75010
    • Investigational Site Number : 2500003
  • Paris, France, 75012
    • Investigational Site Number : 2500001
• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number : 2760006
  • Cologne, Germany, 50937
    • Investigational Site Number : 2760002
  • Frankfurt am Main, Germany, 60590
    • Investigational Site Number : 2760001
  • Hanover, Germany, 30625
    • Investigational Site Number : 2760004
• Italy
  • Genova, Italy, 16132
    • Investigational Site Number : 3800006
  • Verona, Italy, 37134
    • Investigational Site Number : 3800005
  • Vicenza, Italy, 36100
    • Investigational Site Number : 3800004
  • Campania
    • Avellino, Campania, Italy, 83100
      • Investigational Site Number : 3800003
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Investigational Site Number : 3800001
• Japan
  • Okayama-ken
    • Kurashiki-shi, Okayama-ken, Japan, 710-8602
      • Investigational Site Number : 3920003
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Investigational Site Number : 3920001
• Netherlands
  • Amersfoort, Netherlands, 3818 TZ
    • Investigational Site Number : 5280002
• Spain
  • Madrid, Comunidad de
    • Madrid / Madrid, Madrid, Comunidad de, Spain, 28007
      • Investigational Site Number : 7240001
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Investigational Site Number : 8260002
  • London, City of
    • London, London, City of, United Kingdom, NW1 2PG
      • Investigational Site Number : 8260001
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama- Site Number : 8400011
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University- Site Number : 8400007
  • North Carolina
    • Durham, North Carolina, United States, 27710-4000
      • Duke University Medical Center Site Number : 8400022
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center - Site Number : 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by ADAMTS13 testing within 48 hours (2 days).

Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or 2.

A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a woman of nonchildbearing potential (WONCBP), OR
• Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration.

Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.

Exclusion Criteria:

Platelet count ≥100 x 10^9/L. Serum creatinine level >2.26 mg/dL (200 µmol/L) in case platelet count is >30 x 10^9/L (to exclude possible cases of atypical HUS).

Known other causes of thrombocytopenia including but not limited to:

• Clinical evidence of enteric infection with E. coli 0157 or related organism.
• Atypical HUS.
• Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy.
• Known or suspected sepsis.
• Diagnosis of disseminated intravascular coagulation. Congenital TTP (known at the time of study entry). Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia).

Inherited or acquired coagulation disorders. Malignant arterial hypertension. Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.).

Those presenting with severe neurological or cardiac disease. Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy.

Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to:

• vitamin K antagonists.
• direct-acting oral anticoagulants.
• heparin or low molecular weight heparin (LMWH).
• non-steroidal anti-inflammatory molecules other than acetyl salicylic acid. Participants who were previously enrolled in this clinical study (study EFC16521).

Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer.

Positive result on COVID test.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caplacizumab & immunosuppressive therapy without 1st-line TPE; All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody [rituximab or biosimilar]) without first line TPE	Drug: Caplacizumab; Lyophilized powder for solution for injection.; Other Names: Cablivi®; Drug: Corticosteroids; Solution for injection or Tablet; Other Names: Prednisone® /Prednisolone®; Biological: anti-CD20 antibody; Solution for injection; Other Names: rituximab or biosimilar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period	Remission was defined as sustained clinical response with either no TPE and no anti- von Willebrand factor (vWF) therapy for >=30 days (clinical remission) or with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) activity level >=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count >=150 × 10^9/liter (L) and lactate dehydrogenase (LDH) <1.5 × upper limit of normal (ULN) and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Remission During Overall Study Period	Remission was defined as sustained clinical response with either no TPE and no anti- vWF therapy for >=30 days (clinical remission) or with ADAMTS13 activity level >=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count >=150 × 10^9/L and LDH <1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period	TPE was a procedure in which blood of the participant was passed through a medical device which separated out plasma from other components of blood and the participant's plasma was removed and replaced with a replacement solution such as colloid solution (example, albumin and/or plasma) or a combination of crystalloid/colloid solution. TPE replenishes the ADAMTS13 enzyme and removes anti-ADAMTS13 antibodies, and ultra-large von Willebrand factor multimers gradually from the circulation.	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period. SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect, or any other situation where medical or scientific judgment of investigator were exercised. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.	From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks)
Percentage of Participants Who Achieved Clinical Response During On-Treatment Period	Clinical response was defined as sustained platelet count >=150 × 10^9/L and LDH <1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Percentage of Participants Who Achieved Clinical Response During Overall Study Period	Clinical response was defined as sustained platelet count >=150 × 10^9/L and LDH <1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Time to Platelet Count Response	Time to platelet count response was defined as time from start of study treatment to initial platelet count >=150 × 10^9/L that was sustained for >=2 days.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Percentage of Participants Refractory to Therapy During On-Treatment Period	Refractory to therapy was defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts <50 × 10^9/L and persistently elevated LDH (>1.5 × ULN) despite 5 days of treatment during the on-treatment period.	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)-Related Death During On-Treatment Period	Percentage of participants with iTTP-related death during on-treatment period are reported.	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura-Related Death During Overall Study Period	Percentage of participants with iTTP-related death during overall study period are reported.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	Clinical exacerbation was defined as after a clinical response and before a clinical remission, platelet count decreased to <150 × 10^9/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping TPE or anti-vWF therapy.	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	Clinical exacerbation was defined as after a clinical response and before a clinical remission, platelet count decreased to <150 × 10^9/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping TPE or anti-vWF therapy.	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	Clinical relapse was defined as after a clinical remission, platelet count decreased to <150 × 10^9/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A clinical relapse had to be confirmed by documentation of severe ADAMTS13 deficiency (<10%).	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	Clinical relapse was defined as after a clinical remission, platelet count decreased to <150 × 10^9/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A clinical relapse had to be confirmed by documentation of severe ADAMTS13 deficiency (<10%).	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Volker LA, Brinkkotter PT. Tailored treatment of acute immune-mediated thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2025 Dec 5;2025(1):614-620. doi: 10.1182/hematology.2025000757.

Helpful Links

• EFC16521 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Actual): December 26, 2024
• Study Completion (Actual): December 26, 2024

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Thrombophilia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombotic Thrombocytopenic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Proteins; Polycyclic Compounds; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Antibodies, Monoclonal, Murine-Derived; Biological Products; Complex Mixtures; Rituximab; Prednisone; Prednisolone; Biosimilar Pharmaceuticals; Adrenal Cortex Hormones; caplacizumab
• Other Study ID Numbers: EFC16521; U1111-1244-0426 (Registry Identifier: ICTRP); 2022-001177-31 (EudraCT Number); 2024-513262-19 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No