Trial Outcomes & Findings for Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (NCT NCT05468320)

Last Updated: 2025-12-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

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

Results posted on

2025-12-30

Participant Flow

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.

A total of 51 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Caplacizumab and IST Without First-Line TPE Participants received open-label caplacizumab daily and immunosuppressive therapy (IST) (corticosteroid +/-anti-CD20 antibodies \[Ab\] therapy \[rituximab or biosimilar\]) without first-line therapeutic plasma exchange (TPE). Participant received caplacizumab 10 milligram (mg) intravenous (IV) injection for a single dose followed by caplacizumab 10 mg subcutaneous (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/kilogram (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.
Overall Study STARTED	51
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Caplacizumab and IST Without First-Line TPE Participants received open-label caplacizumab daily and immunosuppressive therapy (IST) (corticosteroid +/-anti-CD20 antibodies \[Ab\] therapy \[rituximab or biosimilar\]) without first-line therapeutic plasma exchange (TPE). Participant received caplacizumab 10 milligram (mg) intravenous (IV) injection for a single dose followed by caplacizumab 10 mg subcutaneous (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/kilogram (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.
Overall Study Other	1
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Caplacizumab and IST Without First-Line TPE n=51 Participants 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.
Age, Continuous	46.7 years STANDARD_DEVIATION 14.8 • n=174 Participants
Sex: Female, Male Female	17 Participants n=174 Participants
Sex: Female, Male Male	34 Participants n=174 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=174 Participants
Race (NIH/OMB) Asian	7 Participants n=174 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=174 Participants
Race (NIH/OMB) Black or African American	8 Participants n=174 Participants
Race (NIH/OMB) White	20 Participants n=174 Participants
Race (NIH/OMB) More than one race	0 Participants n=174 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=174 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Who Achieved Remission Without Requirement of Therapeutic Plasma Exchange During Overall Study Period	93.5 percentage of participants Interval 82.5 to 97.8

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Who Achieved Remission During Overall Study Period	95.7 percentage of participants Interval 85.5 to 98.8

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Who Required Therapeutic Plasma Exchange During On-Treatment Period	4.3 percentage of participants Interval 1.2 to 14.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=50 Participants 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.
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
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
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 outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Who Achieved Clinical Response During On-Treatment Period	97.8 percentage of participants Interval 88.7 to 99.6

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Who Achieved Clinical Response During Overall Study Period	97.8 percentage of participants Interval 88.7 to 99.6

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Time to Platelet Count Response	4 days Interval 3.0 to 5.0

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants Refractory to Therapy During On-Treatment Period	2.2 percentage of participants Interval 0.4 to 11.3

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Percentage of participants with iTTP-related death during on-treatment period are reported.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)-Related Death During On-Treatment Period	0 percentage of participants Interval 0.0 to 7.7

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Percentage of participants with iTTP-related death during overall study period are reported.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With Immune-mediated Thrombotic Thrombocytopenic Purpura-Related Death During Overall Study Period	0 percentage of participants Interval 0.0 to 7.7

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	0 percentage of participants Interval 0.0 to 7.7

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With a Clinical Exacerbation of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	0 percentage of participants Interval 0.0 to 7.7

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

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%).

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During On-Treatment Period	0 percentage of participants Interval 0.0 to 7.7

SECONDARY outcome

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

Population: The mITT population consisted of all enrolled participants who received at least 1 dose of the study treatment with an evaluable primary endpoint.

Outcome measures

Outcome measures
Measure	Caplacizumab and IST Without First-Line TPE n=46 Participants 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.
Percentage of Participants With a Clinical Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura During Overall Study Period	0 percentage of participants Interval 0.0 to 7.7

Adverse Events

Caplacizumab and IST Without First-Line TPE

Serious events: 7 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Caplacizumab and IST Without First-Line TPE n=50 participants at risk 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.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Immune system disorders Anaphylactic Reaction	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Metabolism and nutrition disorders Steroid Diabetes	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Renal and urinary disorders Acute Kidney Injury	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Reproductive system and breast disorders Heavy Menstrual Bleeding	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Investigations Platelet Count Decreased	2.0% 1/50 • Number of events 1 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.

Other adverse events

Other adverse events
Measure	Caplacizumab and IST Without First-Line TPE n=50 participants at risk 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.
Nervous system disorders Hypoaesthesia	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Vascular disorders Haematoma	8.0% 4/50 • Number of events 7 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Vascular disorders Hypertension	6.0% 3/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.0% 7/50 • Number of events 8 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Gastrointestinal disorders Constipation	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Gastrointestinal disorders Gingival Bleeding	14.0% 7/50 • Number of events 8 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Petechiae	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Rash	6.0% 3/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Back Pain	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
General disorders Fatigue	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
General disorders Injection Site Bruising	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
General disorders Oedema Peripheral	14.0% 7/50 • Number of events 7 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
General disorders Pyrexia	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Investigations Alanine Aminotransferase Increased	16.0% 8/50 • Number of events 8 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Investigations Blood Bilirubin Increased	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Investigations Blood Creatinine Increased	6.0% 3/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Investigations Troponin Increased	6.0% 3/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Injury, poisoning and procedural complications Contusion	10.0% 5/50 • Number of events 6 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Metabolism and nutrition disorders Hyperglycaemia	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Metabolism and nutrition disorders Hypokalaemia	6.0% 3/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Metabolism and nutrition disorders Steroid Diabetes	6.0% 3/50 • Number of events 3 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Psychiatric disorders Middle Insomnia	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Nervous system disorders Dizziness	8.0% 4/50 • Number of events 4 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.
Nervous system disorders Headache	36.0% 18/50 • Number of events 21 • Adverse events collected from first dose of study treatment (Day 1) up to last dose of study treatment + 28 days (approximately 16 weeks). All-cause mortality (death) was assessed from signing of the informed consent form to end of follow-up, approximately 109 weeks. Analysis was performed on safety population.

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