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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05468320

Acronym

MAYARI

Enrollment

Registered

2022-07-21

Start date

2022-11-21

Completion date

2024-12-26

Last updated

2025-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Thrombotic Thrombocytopenic Purpura

Brief summary

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.

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).

Interventions

DRUGCaplacizumab

Lyophilized powder for solution for injection.

DRUGCorticosteroids

Solution for injection or Tablet

BIOLOGICALanti-CD20 antibody

Solution for injection

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks	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.
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)-Related Death During 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 iTTP-related death during on-treatment period are reported.
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura-Related Death During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	Percentage of participants with iTTP-related death during overall study period are reported.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)	From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks)	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.
Percentage of Participants Who Achieved Clinical Response During On-Treatment Period	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks	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.
Percentage of Participants Who Achieved Clinical Response During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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.
Percentage of Participants Who Achieved Remission During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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.
Percentage of Participants Refractory to Therapy During On-Treatment Period	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks	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.
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks	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.
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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.
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks	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%).
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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%).
Time to Platelet Count Response	From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)	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.

Countries

Belgium, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States

Participant flow

Recruitment details

The study was conducted at 27 centers in 11 countries. A total of 58 participants were screened between 21 November 2022 and 24 June 2024, of which 2 were screen failures, and 5 participants treated with at least 1 dose of caplacizumab were not enrolled due to not meeting study eligibility criteria.

Pre-assignment details

A total of 51 participants were enrolled in the study.

Participants by arm

Arm	Count
Caplacizumab and IST Without First-Line TPE Participants received open-label caplacizumab daily and IST (corticosteroid +/-anti-CD20 Ab therapy \[rituximab or biosimilar\]) without first-line TPE. Participant received caplacizumab 10 mg IV injection for a single dose followed by caplacizumab 10 mg SC injection 4 to 6 hours after the IV dose on Day 1. Then participants received caplacizumab 10 mg SC injection daily starting on Day 2 for a maximum treatment duration of 12 weeks. Participants also received corticosteroids (prednisone or prednisolone) 1 to 1.5 mg/kg/day, IV or oral for 1 week and taper over 3 to 4 weeks, along with anti-CD20 Ab therapy at the beginning of the study. Participants did not receive TPE as first-line therapy, however, they could receive TPE if it was determined that there was a lack of adequate response to study treatment or if there was any clinical deterioration at any time during the study, including during the first 24 hours.	51
Total	51

Arm

Count

Caplacizumab and IST Without First-Line TPE

Participants received open-label caplacizumab daily and IST (corticosteroid +/-anti-CD20 Ab therapy \[rituximab or biosimilar\]) without first-line TPE. Participant received caplacizumab 10 mg IV injection for a single dose followed by caplacizumab 10 mg SC injection 4 to 6 hours after the IV dose on Day 1. Then participants received caplacizumab 10 mg SC injection daily starting on Day 2 for a maximum treatment duration of 12 weeks. Participants also received corticosteroids (prednisone or prednisolone) 1 to 1.5 mg/kg/day, IV or oral for 1 week and taper over 3 to 4 weeks, along with anti-CD20 Ab therapy at the beginning of the study. Participants did not receive TPE as first-line therapy, however, they could receive TPE if it was determined that there was a lack of adequate response to study treatment or if there was any clinical deterioration at any time during the study, including during the first 24 hours.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Other	1

Baseline characteristics

Characteristic	Caplacizumab and IST Without First-Line TPE
Age, Continuous	46.7 years STANDARD_DEVIATION 14.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	7 Participants
Race (NIH/OMB) Black or African American	8 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants
Race (NIH/OMB) White	20 Participants
Sex: Female, Male Female	17 Participants
Sex: Female, Male Male	34 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 50
other Total, other adverse events	40 / 50
serious Total, serious adverse events	7 / 50

Outcome results

Primary

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.

Time frame: From first dose of study treatment (Day 1) up to end of follow-up (up to approximately 24 weeks)

Population: The modified intent-to-treat (mITT) population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Arm	Measure	Value (NUMBER)
Caplacizumab and IST Without First-Line TPE	Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period	93.5 percentage of participants

Secondary

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.

Time frame: From first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks)

Population: The safety population consisted of all enrolled participants who took at least 1 dose of the study treatment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Caplacizumab and IST Without First-Line TPE	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)	TEAEs	46 Participants
Caplacizumab and IST Without First-Line TPE	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)	TESAEs	7 Participants
Caplacizumab and IST Without First-Line TPE	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESI)	TEAESI	8 Participants

Secondary

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.

Time frame: From first dose of study treatment (Day 1) up to last dose of study treatment, approximately 12 weeks