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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT02878603

Collaborator

(none)

104

Enrollment

Locations

Arm

48.6

Actual Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acquired Thrombotic Thrombocytopenic Purpura	Biological: Caplacizumab Other: Standard of Care	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 6, 2016

Actual Primary Completion Date :

Oct 23, 2020

Actual Study Completion Date :

Oct 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: caplacizumab Participants who completed study ALX0681-C301 (NCT02553317) with standard of care (plasma exchange [PE], corticosteroid and other immunosuppressive agents) or 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 investigational medicinal product [IMP], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 milligrams (mg) intravenous dose followed by a daily 10 mg subcutaneous 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.	Biological: Caplacizumab Other: Standard 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).

Arm

Intervention/Treatment

Experimental: caplacizumab

Participants who completed study ALX0681-C301 (NCT02553317) with standard of care (plasma exchange [PE], corticosteroid and other immunosuppressive agents) or 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 investigational medicinal product [IMP], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 milligrams (mg) intravenous dose followed by a daily 10 mg subcutaneous 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.

Biological: Caplacizumab

Other: Standard 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).

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator site	Saint Louis	Missouri	United States	63110
2	Investigator site	Valhalla	New York	United States	10595
3	Investigator Site	Durham	North Carolina	United States	27710
4	Investigator Site	Columbus	Ohio	United States	43210
5	Investigator Site	Oklahoma City	Oklahoma	United States	73104
6	Investigator site	Pittsburgh	Pennsylvania	United States	15232
7	Investigator Site	Charleston	South Carolina	United States	29425
8	Investigator site	Greenville	South Carolina	United States	27834
9	Investigator site	Vienna		Austria
10	Investigator site	Antwerp		Belgium
11	Investigator site	Bruxelles		Belgium
12	Investigator site	La Louviere		Belgium
13	Investigator site	Leuven		Belgium
14	Investigator Site	Halifax		Canada
15	Investigator Site	Quebec		Canada
16	Investigator Site	Toronto		Canada
17	Investigator Site	Brno		Czechia
18	Investigator Site	Olomouc		Czechia
19	Investigator site	Caen		France
20	Investigator site	Lille		France
21	Investigator site	Marseille		France
22	Investigator site 1	Paris		France
23	Investigator site 2	Paris		France
24	Investigator Site	Budapest		Hungary
25	Investigator Site	Debrecen		Hungary
26	Investigator Site	Haifa		Israel
27	Investigator Site	Jerusalem Region		Israel
28	Investigator Site	Nahariya		Israel
29	Investigator Site	Catania		Italy
30	Investigator Site	Milan		Italy
31	Investigator site	Pesaro		Italy
32	Investigator Site	Rome		Italy
33	Investigator Site	Vicenza		Italy
34	Investigator Site 1	Barcelona		Spain
35	Investigator Site 2	Barcelona		Spain
36	Investigator site	Sevilla		Spain
37	Investigator Site 2	Valencia		Spain
38	Investyigator Site 1	Valencia		Spain
39	Investigator site	Bern		Switzerland
40	Investigator site	Ankara		Turkey
41	Investigator site	Istanbul		Turkey
42	Investigator site	Kayseri		Turkey
43	Investigator Site	Bristol		United Kingdom
44	Investigator site	Liverpool		United Kingdom
45	Investigator Site	London		United Kingdom

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Medical Director Ablynx, MD, Ablynx NV

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT02878603

Other Study ID Numbers:

LTS16371
2016-001503-23
ALX0681-C302

First Posted:

Aug 25, 2016

Last Update Posted:

Mar 28, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Purpura

Purpura, Thrombocytopenic

Purpura, Thrombotic Thrombocytopenic

Study Results

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 Detail	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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	29	75
COMPLETED	23	70
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)	Total Title
Arm/Group Description	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.	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 Participants	29	75	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (14.8)	46.0 (11.9)	47.5 (12.9)
Sex: Female, Male (Count of Participants)
Female	23 79.3%	51 68%	74 71.2%
Male	6 20.7%	24 32%	30 28.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	3 4%	3 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 20.7%	13 17.3%	19 18.3%
White	21 72.4%	52 69.3%	73 70.2%
More than one race	0 0%	2 2.7%	2 1.9%
Unknown or Not Reported	2 6.9%	5 6.7%	7 6.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) Related Events
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [percentage of participants]	37.9 130.7%	8.2 10.9%

2. Primary Outcome

Title	Number of Acquired Thrombotic Thrombocytopenic Purpura-related Events
Description	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 Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [aTTP-related events]	11	4

3. Primary Outcome

Title	Time to First Acquired Thrombotic Thrombocytopenic Purpura-related Events
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Median (95% Confidence Interval) [days]	NA	NA

4. Primary Outcome

Title	Number of Participants With aTTP Related Deaths Reported During the Study
Description
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Count of Participants [Participants]	1 3.4%	0 0%

5. Primary Outcome

Title	Percentage of Participants With Recurrence of Disease (aTTP)
Description	Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [percentage of participants]	27.6 95.2%	8.2 10.9%

6. Primary Outcome

Title	Number of Disease (aTTP) Recurrence Reported During the Study
Description	Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [aTTP recurrences]	8	4

7. Primary Outcome

Title	Time to Recurrence of Disease (aTTP)
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Median (95% Confidence Interval) [days]	NA	NA

8. Primary Outcome

Title	Percentage of Participants With Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura (TTP)
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [percentage of participants]	37.9 130.7%	8.2 10.9%

9. Primary Outcome

Title	Number of Major Thromboembolic Events Including Thrombotic Thrombocytopenic Purpura
Description	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 Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Number [major thromboembolic events]	11	4

10. Primary Outcome

Title	Time to First Major Thromboembolic Event
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Median (95% Confidence Interval) [days]	NA	NA

11. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	89.7 (20.3)	92.7 (14.9)
At 36 Months	98.0 (16.6)	96.5 (17.0)
Change at 36 Months	2.1 (8.7)	4.2 (8.9)

12. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	45.0 (10.0)	48.2 (9.9)
Change at 12 Months	0.9 (6.5)	0.1 (7.0)
Change at 24 Months	1.2 (8.2)	-0.6 (8.7)
Change at 36 Months	0.6 (7.9)	1.4 (7.5)

13. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	68.3 (28.9)	74.1 (23.6)
Change at 12 Months	1.3 (16.8)	1.5 (24.1)
Change at 24 Months	-0.8 (18.2)	5.7 (19.3)
Change at 36 Months	5.7 (17.4)	6.2 (18.9)

14. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	60.1 (31.9)	65.9 (30.6)
Change at 12 Months	-5.3 (19.3)	7.7 (35.4)
Change at 24 Months	4.1 (24.1)	7.1 (28.0)
Change at 36 Months	5.8 (20.0)	3.6 (28.6)

15. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	75.3 (25.6)	75.0 (29.4)
Change at 12 Months	-13.2 (31.0)	1.6 (38.0)
Change at 24 Months	-1.3 (32.5)	0.9 (33.7)
Change at 36 Month	-4.4 (20.6)	-3.7 (29.6)

16. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	50.9 (21.2)	52.4 (20.9)
Change at 12 Months	-0.3 (18.3)	2.0 (20.7)
Change at 24 Months	5.9 (21.4)	0.6 (21.7)
Change at 36 Months	7.5 (21.3)	3.9 (18.7)

17. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	72.1 (18.3)	70.1 (20.7)
Change at 12 Months	-9.3 (18.2)	-2.5 (21.1)
Change at 24 Months	-3.3 (18.9)	-2.0 (21.3)
Change at 36 Months	-0.7 (14.6)	-1.5 (19.3)

18. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	74.6 (25.3)	74.0 (28.5)
Change at 12 Months	-10.6 (26.7)	1.6 (35.1)
Change at 24 Months	0.0 (27.5)	-0.8 (33.8)
Change at 36 Months	0.8 (18.0)	-2.6 (31.9)

19. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	68.4 (31.7)	68.0 (23.5)
Change at 12 Months	-1.8 (30.4)	0.3 (33.6)
Change at 24 Months	-9.4 (32.5)	5.0 (24.9)
Change at 36 Months	-5.2 (21.5)	3.7 (25.6)

20. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	66.4 (18.5)	53.1 (19.3)
Change at 12 Months	-4.0 (19.8)	4.9 (19.0)
Change at 24 Months	-1.5 (17.9)	4.8 (20.9)
Change at 36 Months	-4.7 (11.1)	3.6 (17.3)

21. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	49
Baseline	45.7 (31.4)	53.6 (34.2)
Change at 12 Months	30.0 (40.2)	20.1 (44.0)
Change at 24 Months	21.3 (36.5)	10.6 (39.0)
Change at 36 Months	16.7 (33.6)	4.7 (37.1)

22. Primary Outcome

Title	Percentage of Participants With Drug-induced Treatment-emergent (TE) Anti-drug Antibodies (ADA) Positive Response
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	75
Number [percentage of participants]	0 0%	10.7 14.3%

23. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	From Baseline up to 36 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)	Caplacizumab (Treated in Study C301)
Arm/Group Description	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.	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.
Measure Participants	29	75
At least one AE	26 89.7%	68 90.7%
At least one SAE	16 55.2%	28 37.3%
At least one AE leading to death	1 3.4%	0 0%

Adverse Events

	Standard of Care (SoC) (Treated in Study C301)		Caplacizumab (Treated in Study C301)
Time Frame	From Baseline up to 36 months
Adverse Event Reporting Description	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.

Arm/Group Title	Standard of Care (SoC) (Treated in Study C301)		Caplacizumab (Treated in Study C301)
Arm/Group Description	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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/75 (0%)
Serious Adverse Events
	Standard of Care (SoC) (Treated in Study C301)		Caplacizumab (Treated in Study C301)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/29 (55.2%)		28/75 (37.3%)
Blood and lymphatic system disorders
Lymphadenitis	0/29 (0%)	0	1/75 (1.3%)	1
Thrombotic Thrombocytopenic Purpura	8/29 (27.6%)	9	11/75 (14.7%)	21
Cardiac disorders
Acute Myocardial Infarction	1/29 (3.4%)	1	0/75 (0%)	0
Angina Unstable	1/29 (3.4%)	1	0/75 (0%)	0
Pericarditis	1/29 (3.4%)	3	0/75 (0%)	0
Gastrointestinal disorders
Gastrointestinal Haemorrhage	0/29 (0%)	0	1/75 (1.3%)	1
Ileus	1/29 (3.4%)	1	0/75 (0%)	0
Infections and infestations
Appendicitis	0/29 (0%)	0	1/75 (1.3%)	1
Cellulitis	0/29 (0%)	0	1/75 (1.3%)	1
Hepatitis Viral	1/29 (3.4%)	1	0/75 (0%)	0
Localised Infection	1/29 (3.4%)	1	0/75 (0%)	0
Lower Respiratory Tract Infection	0/29 (0%)	0	1/75 (1.3%)	1
Meningitis Aseptic	0/29 (0%)	0	1/75 (1.3%)	1
Ophthalmic Herpes Zoster	0/29 (0%)	0	1/75 (1.3%)	1
Pneumonia	0/29 (0%)	0	2/75 (2.7%)	3
Pneumonia Pneumococcal	0/29 (0%)	0	1/75 (1.3%)	1
Upper Respiratory Tract Infection	1/29 (3.4%)	1	0/75 (0%)	0
Urinary Tract Infection	0/29 (0%)	0	1/75 (1.3%)	1
Injury, poisoning and procedural complications
Allergic Transfusion Reaction	0/29 (0%)	0	1/75 (1.3%)	1
Musculoskeletal and connective tissue disorders
Back Pain	2/29 (6.9%)	2	0/75 (0%)	0
Osteoarthritis	0/29 (0%)	0	1/75 (1.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/29 (0%)	0	1/75 (1.3%)	1
Invasive Ductal Breast Carcinoma	0/29 (0%)	0	1/75 (1.3%)	1
Plasma Cell Myeloma	0/29 (0%)	0	1/75 (1.3%)	1
Renal Cell Carcinoma	1/29 (3.4%)	1	0/75 (0%)	0
Transitional Cell Carcinoma	1/29 (3.4%)	1	0/75 (0%)	0
Nervous system disorders
Haemorrhage Intracranial	0/29 (0%)	0	1/75 (1.3%)	1
Ischaemic Stroke	0/29 (0%)	0	1/75 (1.3%)	1
Migraine	1/29 (3.4%)	1	0/75 (0%)	0
Seizure	1/29 (3.4%)	1	0/75 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/29 (0%)	0	2/75 (2.7%)	2
Pre-Eclampsia	0/29 (0%)	0	1/75 (1.3%)	1
Psychiatric disorders
Psychotic Disorder	0/29 (0%)	0	1/75 (1.3%)	1
Renal and urinary disorders
Glomerulonephritis Membranous	1/29 (3.4%)	1	0/75 (0%)	0
Haematuria	0/29 (0%)	0	1/75 (1.3%)	1
Haemorrhage Urinary Tract	0/29 (0%)	0	1/75 (1.3%)	1
Renal Infarct	1/29 (3.4%)	1	0/75 (0%)	0
Reproductive system and breast disorders
Colpocele	0/29 (0%)	0	1/75 (1.3%)	1
Hysterocele	0/29 (0%)	0	1/75 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/29 (3.4%)	1	0/75 (0%)	0
Surgical and medical procedures
Abortion Induced	0/29 (0%)	0	2/75 (2.7%)	2
Cholecystectomy	0/29 (0%)	0	1/75 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Standard of Care (SoC) (Treated in Study C301)		Caplacizumab (Treated in Study C301)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/29 (75.9%)		58/75 (77.3%)
Gastrointestinal disorders
Abdominal Pain	2/29 (6.9%)	2	3/75 (4%)	3
Abdominal Pain Upper	3/29 (10.3%)	3	4/75 (5.3%)	4
Constipation	1/29 (3.4%)	1	5/75 (6.7%)	5
Diarrhoea	5/29 (17.2%)	5	5/75 (6.7%)	5
Nausea	1/29 (3.4%)	1	7/75 (9.3%)	7
Toothache	2/29 (6.9%)	2	1/75 (1.3%)	1
General disorders
Asthenia	2/29 (6.9%)	2	0/75 (0%)	0
Fatigue	1/29 (3.4%)	1	7/75 (9.3%)	7
Pyrexia	3/29 (10.3%)	3	3/75 (4%)	3
Immune system disorders
Drug Hypersensitivity	2/29 (6.9%)	2	4/75 (5.3%)	5
Hypersensitivity	2/29 (6.9%)	2	1/75 (1.3%)	1
Infections and infestations
Bronchitis	0/29 (0%)	0	5/75 (6.7%)	5
Herpes Zoster	2/29 (6.9%)	2	2/75 (2.7%)	2
Influenza	3/29 (10.3%)	3	7/75 (9.3%)	7
Lower Respiratory Tract Infection	2/29 (6.9%)	2	4/75 (5.3%)	4
Nasopharyngitis	6/29 (20.7%)	6	6/75 (8%)	6
Rhinitis	2/29 (6.9%)	2	2/75 (2.7%)	2
Tonsillitis	2/29 (6.9%)	2	1/75 (1.3%)	1
Tooth Abscess	2/29 (6.9%)	2	0/75 (0%)	0
Upper Respiratory Tract Infection	3/29 (10.3%)	3	7/75 (9.3%)	7
Urinary Tract Infection	3/29 (10.3%)	3	4/75 (5.3%)	5
Injury, poisoning and procedural complications
Contusion	2/29 (6.9%)	2	2/75 (2.7%)	2
Investigations
Adamts13 Activity Decreased	0/29 (0%)	0	13/75 (17.3%)	13
Blood Cholesterol Increased	0/29 (0%)	0	4/75 (5.3%)	4
Metabolism and nutrition disorders
Hypercholesterolaemia	2/29 (6.9%)	2	2/75 (2.7%)	2
Hypokalaemia	2/29 (6.9%)	2	2/75 (2.7%)	2
Iron Deficiency	1/29 (3.4%)	1	5/75 (6.7%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	2/29 (6.9%)	2	8/75 (10.7%)	8
Back Pain	2/29 (6.9%)	2	4/75 (5.3%)	4
Nervous system disorders
Dizziness	2/29 (6.9%)	2	10/75 (13.3%)	10
Headache	9/29 (31%)	9	16/75 (21.3%)	17
Paraesthesia	5/29 (17.2%)	5	4/75 (5.3%)	4
Seizure	2/29 (6.9%)	2	1/75 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/29 (10.3%)	3	7/75 (9.3%)	7
Skin and subcutaneous tissue disorders
Erythema	2/29 (6.9%)	2	0/75 (0%)	0
Pruritus	1/29 (3.4%)	1	6/75 (8%)	7
Rash	0/29 (0%)	0	5/75 (6.7%)	5
Urticaria	1/29 (3.4%)	1	4/75 (5.3%)	4
Vascular disorders
Hypertension	3/29 (10.3%)	3	1/75 (1.3%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	Trial Transparency Team
Organization	Sanofi aventis recherche & développement
Phone	800-633-1610 ext 6#
Email	Contact-US@sanofi.com

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT02878603

Other Study ID Numbers:

LTS16371
2016-001503-23
ALX0681-C302

First Posted:

Aug 25, 2016

Last Update Posted:

Mar 28, 2022

Last Verified:

Mar 1, 2022

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

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