As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

Modified Full Analysis Set(mFAS): all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 because TAK-755 was unavailable.For participants enrolled prior to Nov 2017,only first 6 months of SoC treatment in period 1 was included in analysis.Overall number of participants analyzed:number of participants with data available for analyses.

Percentage of acute TTP events responding to TAK-755, was defined as not requiring the use of another human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.

mFAS:all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov.2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov 2017,only first 6 months of SoC treatment in period 1 was included in analysis.Overall number of participants: participants with acute TTP events that were confirmed by central lab data treated with TAK-755.

Time to resolution of acute TTP events following initiation of treatment with TAK-755 or SoC agent was assessed. Acute TPP events were considered resolved when: (a) Platelet count was >150,000 per microliter (μL) or drop of platelet count was within 25 percent (%) of baseline, whichever occurred first, and (b) Elevation of lactate dehydrogenase (LDH) <1.5 x baseline or <1.5 x upper limit of normal (ULN). As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the prophylaxis treatment Periods, partitioned per treatment received (TAK-755 and SoC) for the on demand and prophylactic cohorts.

mFAS: all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017,only first 6 months of SoC treatment in period 1 was included in analysis.Overall number of participants analyzed:number of participants with acute TTP events that were confirmed by central lab data.

Thrombocytopenia was defined as a decrease in platelet count ≥25 % of baseline or a platelet count <150,000/μL, reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Microangiopathic hemolytic anemia was defined as an elevation of LDH >1.5* of baseline or >1.5*ULN (with a possible evidence of schistocytes on blood smear) and was reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Neurological symptoms (TTP related) (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures), were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Renal dysfunction was defined as an increase in serum creatinine >1.5*baseline. Number of participants with renal dysfunction were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Number of participants with abdominal pain (TTP related) were reported by treatment arm for the prophylaxis cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Number of supplemental doses prompted by subacute TTP events were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Number of participants with dose modification not prompted by an acute TTP event were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort were reported. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.

mFAS included all FAS participants who were treated according to their randomized treatment sequence with exclusion of those enrolled prior to Nov. 2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 as TAK-755 was unavailable. For participants enrolled prior to Nov. 2017, only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.

AE: Any untoward medical occurrence in participants administered IP that does not necessarily have a causal relationship with treatment. TEAE: AE that has start date-time on/after start date-time of first dose of treatment participant is taking on that assessment/period or if it has start date-time before start date-time of first dose but increases in severity on/after start date-time of the first dose of treatment. SAE: An untoward medical occurrence that at any dose meets 1 or more of following criteria: death; initial/prolonged in-patient hospitalization; life threatening experience; persistent/significant disability/incapacity; congenital anomaly, medically important event (may not be immediately life threatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes). Vital signs, clinical chemistry, hematology as assessed by the investigator were reported as AE.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the on demand and prophylaxis cohorts.

Number of participants with inhibitory antibodies to ADAMTS13 were reported. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the prophylaxis cohorts only.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. Overall number of participants analyzed is the number of participants with at least one assessment of the targeted parameter in the specified treatment.

Total quantity of ADAMTS13 administered during the treatment of acute TTP events (all acute TTP events irrespective of central lab confirmation were included) was assessed. Acute TTP events typically require 3 to 4 days of intensified treatment. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. Overall number of participants analyzed is the number of participants with at least one assessment of the targeted parameter in the specified treatment.

ADAMTS13 activity was measured by the fluorescent resonance energy transfer (FRETS) assay. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 activity level. IR of ADAMTS13 activity for SoC agent and TAK-755 in plasma was assessed. (IU/mL)/(IU/kg) stands for (International units per milliliter)/(International units per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

ADAMTS13 antigen was measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 antigen. IR of ADAMTS13 antigen for SoC agent and TAK-755 in plasma was assessed. (µg/mL)/ (µg/kg) stands for (microgram per milliliter)/(microgram per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

h*IU/mL denotes for hours*international units per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

h*µg/mL denotes for hours*microgram per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

IU/mL stands for International units per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth,Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

µg/mL stands for microgram per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

VWF:Ag is a measure of total VWF protein and was assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment were reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The Pharmacodynamic (PD) Analysis Set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

VWF:RCo provides a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo at baseline and following infusion of the SoC agent and TAK-755 treatment during the initial PK assessment was reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD Analysis Set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria [TAK-755 ORT], rADAMTS13 manufactured in Singapore [TAK-755 SIN], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.

The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.

Total binding antibodies to ADAMTS13 were measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. 2 participants randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II and are presented per actual treatment arm.

Neutralizing antibodies were measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. 2 participants randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II and are presented per actual treatment arm.

Total immunoglobulin antibodies (Immunoglobulin G [IgG], A [IgA], and M [IgM]) against CHO protein were analyzed using ELISA assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.

The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. 2 participants randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II and are presented per actual treatment arm.

The cTTP-PEQ consists of 26 questions designed to assess the participant's experience of fatigue, joint, muscle, abdominal &chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and participant's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PEQ is focused on measuring the symptoms and impacts of disease. The total scores range from 0 to 162. A higher score indicates greater burden and poor quality of life. As per planned analysis,for the prophylaxis cohorts the data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups,≥12 years,12 to 18 years,≥18 years for both on demand(OD) and prophylaxis cohorts. No participants in the OD Cohorts had cTTP-PEQ data available for analysis at scheduled post-baseline visits.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category.

SF-36v2 is questionnaire that evaluated participant's health related quality of life. It included 36 questions related to 8 health dimensions: physical functioning, role-physical(role limitations due to physical health problems), bodily pain, general health, vitality(energy/fatigue),social functioning, role-emotional(role limitations due to emotional problems),& mental health. Based on these 4 scales(physical functioning, role-physical, bodily pain, general health), physical component score was generated which ranges between 0 &100, with higher scores indicating a better quality of life. Based on these 4 scales(vitality, social functioning, role-emotional,&mental health), mental component score was generated ranging between 0&100, with higher scores=better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected&reported by categorizing as per Prophylaxis Periods and per component scores for both on demand&prophylaxis cohorts.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category. No participants in the OD Cohorts had SF-36v2 data available for analysis at scheduled post-baseline visits.

TSQM is a treatment satisfaction measure used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are treatment effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicates greater satisfaction in that domain. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category. No participants in the OD Cohorts had TSQM-9 data available for analysis at scheduled post-baseline visits.

EQ-5D-3L health questionnaire is a participant-answered questionnaire scoring 5 dimensions(domains) - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. Lower scores for the domains in the EQ-5D-3L indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category. No participants in the OD Cohorts had EQ-5D-3L data available for analysis at scheduled post-baseline visits.

EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions (domains) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed in participants aged from 8 to 16 years. The EQ-5D-Y descriptive system includes 5 descriptive items: Mobility, self-care, doing usual activities, having pain or discomfort, and feeling anxiety or depressed. Each dimension is scored at 3 levels: 1=No problems, 2=some problems, and 3=a lot of problems. Lower scores for the domains in the EQ-5D-Y indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category. No participants in the OD Cohorts had EQ-5D-Y data available for analysis at scheduled post-baseline visits.

The PedsQL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consists of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups, 2 to < 5 years, 5 to < 8 years, 8 to < 13 years, and 13 to < 18 years, for both on demand and prophylaxis cohorts.

Modified FAS. Overall number of participants analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for specified category. No participants in the OD Cohorts had Peds QL data available for analysis at scheduled post-baseline visits.

The annualized number of days participants stayed in hospital for acute TTP events were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.

Modified FAS included all FAS participants who were treated according to their randomized treatment sequence with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.

Annualized number of acute care visits was calculated as the number of acute care visits × 365.25/(End date - treatment start date + 1). As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.

Modified FAS included all FAS participants who were treated according to their randomized treatment sequence with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.

Annualized number of days missed from school or work were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.

Modified FAS included all FAS participants who were treated according to their randomized treatment sequence with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.