Trial Outcomes & Findings for Follow-up Study for Patients Who Completed Study ALX0681-C301 (Post-HERCULES) (NCT NCT02878603)

Last Updated: 2022-03-28

Results Overview

aTTP-related events were defined as: aTTP-related death, recurrence of aTTP (defined as recurrent thrombocytopenia requiring initiation of daily PE) or at least one major thromboembolic event (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis). Percentage of participants with at least one aTTP-related events during the study were reported in this outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

104 participants

Primary outcome timeframe

From Baseline up to 36 months

Results posted on

2022-03-28

Participant Flow

Study was conducted at 43 active sites in 13 countries. A total of 104 participants who completed Study ALX0681-C301 (HERCULES; NCT02553317) were enrolled between 06-October-2016 and 27-October-2017 in this current study: LTS16371 (ALX0681-C302).

Participants who were randomized to caplacizumab/placebo and received caplacizumab for recurrence of acquired thrombotic thrombocytopenic purpura (aTTP) in ALX0681-C301 were enrolled in Caplacizumab group, and participants randomized to placebo in ALX0681-C301 were enrolled under Standard of Care (SoC) group in the current study LTS16371.

Participant milestones

Participant milestones
Measure	Standard of Care (SoC) (Treated in Study C301) Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Overall Study STARTED	29	75
Overall Study COMPLETED	23	70
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard of Care (SoC) (Treated in Study C301) Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Overall Study Lost to Follow-up	4	1
Overall Study Withdrawal by Subject	1	1
Overall Study Death	1	0
Overall Study Physician Decision	0	3

Baseline Characteristics

Follow-up Study for Patients Who Completed Study ALX0681-C301 (Post-HERCULES)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=75 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Total Title n=104 Participants
Age, Continuous	51.5 years STANDARD_DEVIATION 14.8 • n=5 Participants	46.0 years STANDARD_DEVIATION 11.9 • n=7 Participants	47.5 years STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	51 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	24 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	52 Participants n=7 Participants	73 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Population: Analysis was performed on efficacy intention-to-observe (efficacy ITO) population which included participants who were enrolled in LTS16371 and did not experience an aTTP recurrence in previous study ALX0681-C301 or prior to the beginning of LTS16371.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Percentage of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) Related Events	37.9 percentage of participants	8.2 percentage of participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Population: Analysis was performed on efficacy ITO population which included participants who were enrolled in LTS16371 and did not experience an aTTP recurrence in previous study ALX0681-C301 or prior to the beginning of LTS16371.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Number of Acquired Thrombotic Thrombocytopenic Purpura-related Events	11 aTTP-related events	4 aTTP-related events

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Time to first aTTP-related events was defined as the duration of time (in days) from Baseline up to first aTTP-related event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Time to First Acquired Thrombotic Thrombocytopenic Purpura-related Events	NA days Interval 845.0 to Median and upper limit of 95% confidence interval (CI) were not calculated due to very few participants with events.	NA days Median, upper and lower limit of 95% CI were not calculated due to very few participants with events.

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Number of Participants With aTTP Related Deaths Reported During the Study	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Percentage of Participants With Recurrence of Disease (aTTP)	27.6 percentage of participants	8.2 percentage of participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Number of Disease (aTTP) Recurrence Reported During the Study	8 aTTP recurrences	4 aTTP recurrences

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Time to first recurrence of disease (aTTP) was defined as the duration of time (in days) from Baseline up to first recurrence of aTTP event in LTS16371. Recurrence of aTTP: defined as recurrent thrombocytopenia requiring initiation of daily PE. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Time to Recurrence of Disease (aTTP)	NA days Interval 1280.0 to Median and upper limit of 95% CI were not calculated due to very few participants with events.	NA days Median, upper and lower limit of 95% CI were not calculated due to very few participants with events.

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Reported major thromboembolic events included TTP recurrences.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Percentage of Participants With Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura (TTP)	37.9 percentage of participants	8.2 percentage of participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on SMQ. Reported major thromboembolic events included TTP recurrences.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Number of Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura	11 major thromboembolic events	4 major thromboembolic events

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Time to first major thromboembolic event was defined as the duration of time (in days) from Baseline up to first major thromboembolic event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Time to First Major Thromboembolic Event	NA days Interval 845.0 to Median, upper limit of 95% CI were not calculated due to very few participants with events.	NA days Median, upper and lower limit of 95% CI were not calculated due to very few participants with events.

PRIMARY outcome

Timeframe: Baseline, 36 Months follow-up visit

Population: Analyzed on efficacy ITO population: participants who were enrolled in LTS16371 and did not experience aTTP recurrence in previous study ALX0681-C301 or prior to beginning of LTS16371. Here, 'number analyzed'=participants with available data for each specified category.

The RBANS is a 30-minute comprehensive screening test with five individual domains (immediate memory, delayed memory, attention, language, and visuospatial ability) to examine the cognitive mental status of a participant. Scores from all individual domain were aggregated into a total score and thus RBANS total score ranged from 40 to 160, where higher scores reflected better performance.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Cognitive Function: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Absolute Scores at Baseline, 36 Months Follow-up Visit, and Change From Baseline in RBANS Total Score at 36 Months Follow-up Visit Baseline	89.7 units on a scale Standard Deviation 20.3	92.7 units on a scale Standard Deviation 14.9
Cognitive Function: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Absolute Scores at Baseline, 36 Months Follow-up Visit, and Change From Baseline in RBANS Total Score at 36 Months Follow-up Visit At 36 Months	98.0 units on a scale Standard Deviation 16.6	96.5 units on a scale Standard Deviation 17.0
Cognitive Function: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Absolute Scores at Baseline, 36 Months Follow-up Visit, and Change From Baseline in RBANS Total Score at 36 Months Follow-up Visit Change at 36 Months	2.1 units on a scale Standard Deviation 8.7	4.2 units on a scale Standard Deviation 8.9

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

HIT-6 is an easy to administer assessment that was used as a clinical evaluation of the impact of headache on a participant's QoL in both clinical practice and clinical research. The questionnaire included 6 questions covering the 6 areas of functioning most impacted in headache sufferers including pain, role functioning (the ability to carry out usual activities), social functioning, vitality (energy/ fatigue), cognitive functioning, and psychological/emotional distress. Total HIT-6 scores (sum of all individual questions) ranged from 36 (best outcome) to 78 (worst outcome), where higher scores indicated worse condition.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life (HRQoL): Change From Baseline in Headache Impact Test (HIT-6) Total Scores at Month 12, 24, and 36 Follow-up Visits Baseline	45.0 units on a scale Standard Deviation 10.0	48.2 units on a scale Standard Deviation 9.9
Health-Related Quality of Life (HRQoL): Change From Baseline in Headache Impact Test (HIT-6) Total Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	0.9 units on a scale Standard Deviation 6.5	0.1 units on a scale Standard Deviation 7.0
Health-Related Quality of Life (HRQoL): Change From Baseline in Headache Impact Test (HIT-6) Total Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	1.2 units on a scale Standard Deviation 8.2	-0.6 units on a scale Standard Deviation 8.7
Health-Related Quality of Life (HRQoL): Change From Baseline in Headache Impact Test (HIT-6) Total Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	0.6 units on a scale Standard Deviation 7.9	1.4 units on a scale Standard Deviation 7.5

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Physical functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in physical functioning domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire (SF-36) Health Survey - Physical Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	68.3 units on a scale Standard Deviation 28.9	74.1 units on a scale Standard Deviation 23.6
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire (SF-36) Health Survey - Physical Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	1.3 units on a scale Standard Deviation 16.8	1.5 units on a scale Standard Deviation 24.1
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire (SF-36) Health Survey - Physical Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	-0.8 units on a scale Standard Deviation 18.2	5.7 units on a scale Standard Deviation 19.3
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire (SF-36) Health Survey - Physical Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	5.7 units on a scale Standard Deviation 17.4	6.2 units on a scale Standard Deviation 18.9

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role Functioning/Physical domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/physical domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Physical Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	60.1 units on a scale Standard Deviation 31.9	65.9 units on a scale Standard Deviation 30.6
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Physical Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-5.3 units on a scale Standard Deviation 19.3	7.7 units on a scale Standard Deviation 35.4
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Physical Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	4.1 units on a scale Standard Deviation 24.1	7.1 units on a scale Standard Deviation 28.0
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Physical Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	5.8 units on a scale Standard Deviation 20.0	3.6 units on a scale Standard Deviation 28.6

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role functioning/emotional domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/emotional domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Emotional Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	75.3 units on a scale Standard Deviation 25.6	75.0 units on a scale Standard Deviation 29.4
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Emotional Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-13.2 units on a scale Standard Deviation 31.0	1.6 units on a scale Standard Deviation 38.0
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Emotional Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	-1.3 units on a scale Standard Deviation 32.5	0.9 units on a scale Standard Deviation 33.7
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Role Functioning/Emotional Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Month	-4.4 units on a scale Standard Deviation 20.6	-3.7 units on a scale Standard Deviation 29.6

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Energy/fatigue domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in energy/fatigue domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Energy/Fatigue Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	50.9 units on a scale Standard Deviation 21.2	52.4 units on a scale Standard Deviation 20.9
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Energy/Fatigue Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-0.3 units on a scale Standard Deviation 18.3	2.0 units on a scale Standard Deviation 20.7
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Energy/Fatigue Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	5.9 units on a scale Standard Deviation 21.4	0.6 units on a scale Standard Deviation 21.7
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Energy/Fatigue Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	7.5 units on a scale Standard Deviation 21.3	3.9 units on a scale Standard Deviation 18.7

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Emotional well-being domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in emotional well-being domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Emotional Well-being Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	72.1 units on a scale Standard Deviation 18.3	70.1 units on a scale Standard Deviation 20.7
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Emotional Well-being Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-9.3 units on a scale Standard Deviation 18.2	-2.5 units on a scale Standard Deviation 21.1
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Emotional Well-being Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	-3.3 units on a scale Standard Deviation 18.9	-2.0 units on a scale Standard Deviation 21.3
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Emotional Well-being Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	-0.7 units on a scale Standard Deviation 14.6	-1.5 units on a scale Standard Deviation 19.3

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Social functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in social functioning domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Social Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	74.6 units on a scale Standard Deviation 25.3	74.0 units on a scale Standard Deviation 28.5
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Social Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-10.6 units on a scale Standard Deviation 26.7	1.6 units on a scale Standard Deviation 35.1
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Social Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	0.0 units on a scale Standard Deviation 27.5	-0.8 units on a scale Standard Deviation 33.8
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Social Functioning Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	0.8 units on a scale Standard Deviation 18.0	-2.6 units on a scale Standard Deviation 31.9

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Pain domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in pain domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Pain Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	68.4 units on a scale Standard Deviation 31.7	68.0 units on a scale Standard Deviation 23.5
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Pain Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-1.8 units on a scale Standard Deviation 30.4	0.3 units on a scale Standard Deviation 33.6
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Pain Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	-9.4 units on a scale Standard Deviation 32.5	5.0 units on a scale Standard Deviation 24.9
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Pain Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	-5.2 units on a scale Standard Deviation 21.5	3.7 units on a scale Standard Deviation 25.6

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. General Health domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in general health domain score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - General Health Domain Scores at Month 12, 24, and 36 Follow-up Visits Baseline	66.4 units on a scale Standard Deviation 18.5	53.1 units on a scale Standard Deviation 19.3
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - General Health Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	-4.0 units on a scale Standard Deviation 19.8	4.9 units on a scale Standard Deviation 19.0
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - General Health Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	-1.5 units on a scale Standard Deviation 17.9	4.8 units on a scale Standard Deviation 20.9
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - General Health Domain Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	-4.7 units on a scale Standard Deviation 11.1	3.6 units on a scale Standard Deviation 17.3

PRIMARY outcome

Timeframe: Baseline, Month 12, 24, and 36 Follow-up visits

The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Change in health status scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in change in health status score at months 12, 24, and 36 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=49 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Change in Health Status Scores at Month 12, 24, and 36 Follow-up Visits Baseline	45.7 units on a scale Standard Deviation 31.4	53.6 units on a scale Standard Deviation 34.2
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Change in Health Status Scores at Month 12, 24, and 36 Follow-up Visits Change at 12 Months	30.0 units on a scale Standard Deviation 40.2	20.1 units on a scale Standard Deviation 44.0
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Change in Health Status Scores at Month 12, 24, and 36 Follow-up Visits Change at 24 Months	21.3 units on a scale Standard Deviation 36.5	10.6 units on a scale Standard Deviation 39.0
Health-Related Quality of Life: Change From Baseline in 36-Item Short Form Questionnaire Health Survey - Change in Health Status Scores at Month 12, 24, and 36 Follow-up Visits Change at 36 Months	16.7 units on a scale Standard Deviation 33.6	4.7 units on a scale Standard Deviation 37.1

PRIMARY outcome

Timeframe: From Baseline up to 36 months

Population: Analysis was performed on overall ITO population which included participants who were enrolled in LTS16371, grouped by whether they received caplacizumab during previous study ALX0681-C301 versus those who never received caplacizumab before enrollment in LTS16371.

Drug-induced TE ADA positive was based on the outcome of a tiered assay approach that included a modified ADA (mADA) method to eliminate the effects of pre-existing antibodies (pre-Ab). TE ADA responses reported here included both pre-Ab positive and negative responses. A participant was considered as drug-induced TE ADA positive if post-dose samples were positive, regardless of the status of pre-dose samples in the ADA and modified ADA assay.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=75 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Percentage of Participants With Drug-induced Treatment-emergent (TE) Anti-drug Antibodies (ADA) Positive Response	0 percentage of participants	10.7 percentage of participants

PRIMARY outcome

Timeframe: From Baseline up to 36 months

An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was 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, was a congenital anomaly/birth defect, was a medically important event.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) (Treated in Study C301) n=29 Participants Participants who completed study ALX0681-C301 with SoC (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) treatment were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg intravenous (IV) dose followed by a daily 10 milligrams (mg) subcutaneous (SC) injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.	Caplacizumab (Treated in Study C301) n=75 Participants Participants who completed study ALX0681-C301 and received caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to IMP, withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 mg IV dose followed by a daily 10 mg SC injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) At least one AE	26 Participants	68 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) At least one SAE	16 Participants	28 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) At least one AE leading to death	1 Participants	0 Participants

Adverse Events

Standard of Care (SoC) (Treated in Study C301)

Serious events: 16 serious events

Other events: 22 other events

Deaths: 1 deaths

Caplacizumab (Treated in Study C301)

Serious events: 28 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER