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

Prospective Follow-up Study for Patients Who Completed Study ALX0681-C301 (HERCULES) to Evaluate Long-term Safety and Efficacy of Caplacizumab (Post-HERCULES)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02878603

Enrollment

104

Registered

2016-08-25

Start date

2016-10-06

Completion date

2020-10-23

Last updated

2022-03-28

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

Conditions

Acquired Thrombotic Thrombocytopenic Purpura

Brief summary

The objectives of this study were to evaluate long-term safety and efficacy of caplacizumab, to evaluate safety and efficacy of repeated use of caplacizumab and to characterize long-term impact of acquired thrombotic thrombocytopenic purpura (aTTP).

Interventions

BIOLOGICALCaplacizumab

OTHERStandard of Care

• PE with plasma (e.g., fresh frozen plasma, solvent detergent/viral-inactivated plasma, cryosupernatant), • Corticosteroid treatment and • Use of other immunosuppressive agents (e.g., rituximab).

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Completed the Final (28 day) follow-up visit in Study ALX0681-C301. 2. \>= 18 years of age at the time of signing the informed consent form. 3. Provided informed consent prior to initiation of any study specific activity/procedure.

Exclusion criteria

1. Not being able/willing to comply with the study protocol procedures. 2. Currently enrolled in a clinical study with another investigational drug or device.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) Related Events	From Baseline up to 36 months	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.
Number of Acquired Thrombotic Thrombocytopenic Purpura-related Events	From Baseline up to 36 months	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).
Time to First Acquired Thrombotic Thrombocytopenic Purpura-related Events	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.
Number of Participants With aTTP Related Deaths Reported During the Study	From Baseline up to 36 months	—
Percentage of Participants With Recurrence of Disease (aTTP)	From Baseline up to 36 months	Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Number of Disease (aTTP) Recurrence Reported During the Study	From Baseline up to 36 months	Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Time to Recurrence of Disease (aTTP)	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.
Percentage of Participants With Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura (TTP)	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.
Number of Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura	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.
Time to First Major Thromboembolic Event	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.
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, 36 Months follow-up visit	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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
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, 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.
Percentage of Participants With Drug-induced Treatment-emergent (TE) Anti-drug Antibodies (ADA) Positive Response	From Baseline up to 36 months	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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.

Countries

Austria, Belgium, Canada, Czechia, France, Hungary, Israel, Italy, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

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).

Pre-assignment details

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.

Participants by arm

Arm	Count
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.	29
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.	75
Total Title	104
Total	208

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	1	0
Overall Study	Lost to Follow-up	4	1
Overall Study	Physician Decision	0	3
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Caplacizumab (Treated in Study C301)	Total Title	Standard of Care (SoC) (Treated in Study C301)
Age, Continuous	46.0 years STANDARD_DEVIATION 11.9	47.5 years STANDARD_DEVIATION 12.9	51.5 years STANDARD_DEVIATION 14.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	3 Participants	3 Participants	0 Participants
Race (NIH/OMB) Black or African American	13 Participants	19 Participants	6 Participants
Race (NIH/OMB) More than one race	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants	7 Participants	2 Participants
Race (NIH/OMB) White	52 Participants	73 Participants	21 Participants
Sex: Female, Male Female	51 Participants	74 Participants	23 Participants
Sex: Female, Male Male	24 Participants	30 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 29	0 / 75
other Total, other adverse events	22 / 29	58 / 75
serious Total, serious adverse events	16 / 29	28 / 75

Outcome results

Primary

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

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	4.2 units on a scale	Standard Deviation 8.9
Caplacizumab (Treated in Study C301)	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	92.7 units on a scale	Standard Deviation 14.9
Caplacizumab (Treated in Study C301)	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	96.5 units on a scale	Standard Deviation 17

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	4.7 units on a scale	Standard Deviation 37.1
Caplacizumab (Treated in Study C301)	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	53.6 units on a scale	Standard Deviation 34.2
Caplacizumab (Treated in Study C301)	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	10.6 units on a scale	Standard Deviation 39
Caplacizumab (Treated in Study C301)	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	20.1 units on a scale	Standard Deviation 44

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	-1.5 units on a scale	Standard Deviation 19.3
Caplacizumab (Treated in Study C301)	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	70.1 units on a scale	Standard Deviation 20.7
Caplacizumab (Treated in Study C301)	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	-2.0 units on a scale	Standard Deviation 21.3
Caplacizumab (Treated in Study C301)	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	-2.5 units on a scale	Standard Deviation 21.1

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	3.9 units on a scale	Standard Deviation 18.7
Caplacizumab (Treated in Study C301)	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	52.4 units on a scale	Standard Deviation 20.9
Caplacizumab (Treated in Study C301)	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	0.6 units on a scale	Standard Deviation 21.7
Caplacizumab (Treated in Study C301)	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	2.0 units on a scale	Standard Deviation 20.7

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	3.6 units on a scale	Standard Deviation 17.3
Caplacizumab (Treated in Study C301)	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	53.1 units on a scale	Standard Deviation 19.3
Caplacizumab (Treated in Study C301)	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	4.8 units on a scale	Standard Deviation 20.9
Caplacizumab (Treated in Study C301)	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	4.9 units on a scale	Standard Deviation 19

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	3.7 units on a scale	Standard Deviation 25.6
Caplacizumab (Treated in Study C301)	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	68.0 units on a scale	Standard Deviation 23.5
Caplacizumab (Treated in Study C301)	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	5.0 units on a scale	Standard Deviation 24.9
Caplacizumab (Treated in Study C301)	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	0.3 units on a scale	Standard Deviation 33.6

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	-3.7 units on a scale	Standard Deviation 29.6
Caplacizumab (Treated in Study C301)	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	75.0 units on a scale	Standard Deviation 29.4
Caplacizumab (Treated in Study C301)	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	0.9 units on a scale	Standard Deviation 33.7
Caplacizumab (Treated in Study C301)	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	1.6 units on a scale	Standard Deviation 38

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	3.6 units on a scale	Standard Deviation 28.6
Caplacizumab (Treated in Study C301)	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	65.9 units on a scale	Standard Deviation 30.6
Caplacizumab (Treated in Study C301)	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	7.1 units on a scale	Standard Deviation 28
Caplacizumab (Treated in Study C301)	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	7.7 units on a scale	Standard Deviation 35.4

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	-2.6 units on a scale	Standard Deviation 31.9
Caplacizumab (Treated in Study C301)	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	74.0 units on a scale	Standard Deviation 28.5
Caplacizumab (Treated in Study C301)	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	-0.8 units on a scale	Standard Deviation 33.8
Caplacizumab (Treated in Study C301)	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	1.6 units on a scale	Standard Deviation 35.1

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	6.2 units on a scale	Standard Deviation 18.9
Caplacizumab (Treated in Study C301)	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	74.1 units on a scale	Standard Deviation 23.6
Caplacizumab (Treated in Study C301)	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	5.7 units on a scale	Standard Deviation 19.3
Caplacizumab (Treated in Study C301)	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	1.5 units on a scale	Standard Deviation 24.1

Primary

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

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Standard of Care (SoC) (Treated in Study C301)	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
Caplacizumab (Treated in Study C301)	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	1.4 units on a scale	Standard Deviation 7.5
Caplacizumab (Treated in Study C301)	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	48.2 units on a scale	Standard Deviation 9.9
Caplacizumab (Treated in Study C301)	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	-0.6 units on a scale	Standard Deviation 8.7
Caplacizumab (Treated in Study C301)	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	0.1 units on a scale	Standard Deviation 7

Primary

Number of Acquired Thrombotic Thrombocytopenic Purpura-related Events

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).