Trial Outcomes & Findings for Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP) (NCT NCT03922308)

Last Updated: 2022-12-01

Results Overview

ADAMTS-13 Activity Levels was assessed by fluorescence resonance energy transfer (FRETS) ADAMTS13 activity, with or without SHP655 Supplementation. Schedule A (Days 1, 2, 3, 4, 6, 8, 11, and every 3 days thereafter) or Schedule B (Days 1, 2, 3, 5, 7, 9, 12, and every 3 days thereafter). Data is reported for multiple timepoints as Within 15 minutes pre-PEX and post-PEX; Within 15 minutes, 0.5-3 hours, 4-6 hours post end of investigational product (IP) infusion 1; Within 15 minutes, 0.5-3 hours post end IP infusion 2; 30 minutes pre-IP infusion 2 of Schedule A and Schedule B (up to Day 11 or 12).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Up to Days 11 or 12

Results posted on

2022-12-01

Participant Flow

Participants took part in the study at 12 investigative sites in Canada, France, Great Britain, Spain and United States from 09 October 2019 to 05 August 2021.

Participants with a diagnosis of acquired thrombotic thrombocytopenic purpura (aTTP) were enrolled to receive placebo, SHP655 once daily (QD) and twice daily (BID) in a ratio of 1:1:1 in this study .

Participant milestones

Participant milestones
Measure	Standard of Care (SoC) + Placebo Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Overall Study STARTED	10	9	9
Overall Study Pharmacokinetic Population	10	8	9
Overall Study COMPLETED	9	6	8
Overall Study NOT COMPLETED	1	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard of Care (SoC) + Placebo Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Overall Study Not Meeting Confirmatory Inclusion Criteria	0	1	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Reason not Specified	0	2	1

Baseline Characteristics

Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily PEX followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	Total n=28 Participants Total of all reporting groups
Age, Continuous	41.2 years STANDARD_DEVIATION 10.80 • n=5 Participants	51.9 years STANDARD_DEVIATION 14.81 • n=7 Participants	48.4 years STANDARD_DEVIATION 14.93 • n=5 Participants	47.0 years STANDARD_DEVIATION 13.82 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Days 11 or 12

Population: Pharmacokinetic (PK) Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analyses at the given timepoint.

Outcome measures

PRIMARY outcome

Timeframe: Baseline and end of study (EOS) (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants with data evaluable for analyses. Number analyzed is the number of participants available for analysis.

The platelet counts are reported in units of 10\^9 per liter blood.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Platelet Count Baseline	35.80 10^9 platelets/L Standard Deviation 32.076	27.67 10^9 platelets/L Standard Deviation 17.571	15.38 10^9 platelets/L Standard Deviation 7.463
Platelet Count EOS	278.89 10^9 platelets/L Standard Deviation 79.592	267.00 10^9 platelets/L Standard Deviation 86.906	286.22 10^9 platelets/L Standard Deviation 109.264

PRIMARY outcome

Timeframe: Baseline and EOS (up to approximately 15 months)

The lactate dehydrogenase levels are reported.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Lactate Dehydrogenase (LDH) Levels Baseline	634.6 international units (IU)/L Standard Deviation 378.37	616.3 international units (IU)/L Standard Deviation 478.14	787.8 international units (IU)/L Standard Deviation 188.39
Lactate Dehydrogenase (LDH) Levels EOS	197.3 international units (IU)/L Standard Deviation 42.00	208.8 international units (IU)/L Standard Deviation 75.20	220.4 international units (IU)/L Standard Deviation 69.93

SECONDARY outcome

Timeframe: From start of study drug administration up to 13 weeks (following remission up to 6 months)

Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.

Dose(s) of SHP655 needed to achieve and maintain adequate plasma levels of rADAMTS-13 in order to support induction of remission and to reduce the number of PEX procedures needed for the treatment of acute aTTP episodes was assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months

Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.

Parameters included platelet and LDH counts.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and EOS (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants are ADA positive participants. Number analyzed is the number of participants available for analysis.

Antibody titer indicates the level of the antibodies in a blood sample, defined as the greatest dilution (or lowest concentration) of the blood sample at which an antibody assay (such as ELISA for e.g.), still produces a detectable positive result. Data is presented per titer for ADA positive participants only.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=7 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:20	2 Participants	3 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:40	3 Participants	2 Participants	2 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:80	2 Participants	0 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:160	0 Participants	1 Participants	2 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:320	0 Participants	2 Participants	0 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:640	0 Participants	0 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer Baseline- 1:1280	0 Participants	0 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:20	0 Participants	1 Participants	0 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:40	2 Participants	0 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:80	1 Participants	0 Participants	2 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:2560	0 Participants	1 Participants	0 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:5120	0 Participants	0 Participants	1 Participants
Number of Participants With ADAMTS-13 Binding Antibodies Per Titer EOS- 1:81920	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and EOS (up to approximately 15 months)

NAb titers were summarized (median, minimum and maximum) at baseline and EOS per treatment arms, in those subjects with NAb positive results (NAb positive is defined as titer value \>=0.6 BU/mL).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Inhibitory Autoantibodies (Nab) Titer Levels Baseline	1.25 BU/mL Interval 0.6 to 3.4	1.25 BU/mL Interval 1.0 to 1.8	1.80 BU/mL Interval 0.6 to 4.0
Inhibitory Autoantibodies (Nab) Titer Levels EOS	0.60 BU/mL Interval 0.6 to 0.6	0.70 BU/mL Interval 0.7 to 1.7	4.00 BU/mL Interval 4.0 to 4.0

SECONDARY outcome

Timeframe: At Days 3, 7, 10, 21, 28, 42, 56 and 84

Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed is the number of participants with data available for analyses at given time point.

ADAMTS-13 activity levels in participants receiving additional SHP655 for up to 30 days after the resolution of the thrombotic thrombocytopenic purpura (TTP) episode were assessed. Resolution was defined as a normal platelet count and LDH \<2 ULN for at least 48 hours following initial normalization of platelet count (acute episode period).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=7 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=7 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=6 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 3	0.4602 IU/mL Standard Deviation 0.14328	NA IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	0.1171 IU/mL Standard Deviation 0.28688
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 7	0.3037 IU/mL Standard Deviation 0.26921	0.3180 IU/mL Standard Deviation 0.34714	NA IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 10	0.9021 IU/mL Standard Deviation 0.20520	0.5518 IU/mL Standard Deviation 0.33962	0.4904 IU/mL Standard Deviation 0.46441
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 21	0.8102 IU/mL Standard Deviation 0.52773	0.6264 IU/mL Standard Deviation 0.60971	0.5320 IU/mL Standard Deviation 0.51432
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 28	0.8830 IU/mL Standard Deviation 0.51516	0.8931 IU/mL Standard Deviation 0.41323	0.8632 IU/mL Standard Deviation 0.62848
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 42	0.9968 IU/mL Standard Deviation 0.36745	0.8842 IU/mL Standard Deviation 0.39784	1.055 IU/mL Standard Deviation 0.36080
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 56	1.088 IU/mL Standard Deviation 0.25524	0.9923 IU/mL Standard Deviation 0.33663	1.092 IU/mL Standard Deviation 0.19961
ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS Day 84	0.9708 IU/mL Standard Deviation 0.43831	1.021 IU/mL Standard Deviation 0.65715	0.6051 IU/mL Standard Deviation 0.48113

SECONDARY outcome

Timeframe: Up to 6 months

Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.

End-organ disease status were evaluated for renal, cardiac and neurological diseases.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=7 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=7 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 1	2.744 ratio Standard Deviation 3.3837	NA ratio Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA ratio Standard Deviation NA Mean and SD was not estimable for 1 participant.
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 2	2.587 ratio Standard Deviation 0.92176	3.534 ratio Standard Deviation 2.4373	3.675 ratio Standard Deviation 2.3380
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 3	1.669 ratio Standard Deviation 0.34045	2.134 ratio Standard Deviation 0.45392	2.268 ratio Standard Deviation 1.0679
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 4 or 5	NA ratio Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	2.543 ratio Standard Deviation 0.59576	1.972 ratio Standard Deviation 0.91248
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 6 or 7	NA ratio Standard Deviation NA Mean and SD was not estimable for 1 participant.	NA ratio Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA ratio Standard Deviation NA Mean and SD was not estimable for 1 participant.
Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio FRETS: Day 8 or 9	—	NA ratio Standard Deviation NA Mean and SD was not estimable for 1 participant.	—

SECONDARY outcome

Timeframe: Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 1, 2, 3, 4 or 5 and 6 or 7

Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Number analyzed are the number of participants available for analysis at the specific time point.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS Day 1	3.563 h*IU/mL Standard Deviation 2.5551	19.87 h*IU/mL Standard Deviation 9.1150	12.80 h*IU/mL Standard Deviation 8.4633
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS Day 2	4.461 h*IU/mL Standard Deviation 3.9480	24.16 h*IU/mL Standard Deviation 9.0323	21.97 h*IU/mL Standard Deviation 11.135
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS Day 3	5.590 h*IU/mL Standard Deviation 4.7232	22.75 h*IU/mL Standard Deviation 5.6549	23.49 h*IU/mL Standard Deviation 9.2589
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS Day 4 or 5	9.507 h*IU/mL Standard Deviation 11.592	24.10 h*IU/mL Standard Deviation 11.357	22.05 h*IU/mL Standard Deviation 14.192
AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS Day 6 or 7	NA h*IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA h*IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA h*IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.

SECONDARY outcome

Timeframe: 15 minutes pre-PEX,15 minutes post-PEX,15 minutes, 0.5-3 hours, 4-6 hours post end of IP infusion 1,30 minutes pre-IP infusion 2,15 minutes, 0.5-3 hours post-IP infusion 2 of Schedule A or Schedule B (up to 6 months)

Population: Data could not be analyzed due to sparse sample collections and confounding dosing inputs with daily sequential PEX + SHP655 dosing.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-PEX and post-PEX at multiple timepoints at Days 1, 2, 3, 4 or 5, 6 or 7, 8 or 9, and 11 or 12

Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Number analyzed is the number of participants available for analyses at given time point.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 1	0.4157 IU/mL Standard Deviation 0.17075	2.011 IU/mL Standard Deviation 0.79036	1.653 IU/mL Standard Deviation 1.0655
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 2	0.4951 IU/mL Standard Deviation 0.27178	2.153 IU/mL Standard Deviation 1.1404	2.458 IU/mL Standard Deviation 1.4369
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 3	0.4307 IU/mL Standard Deviation 0.28420	2.228 IU/mL Standard Deviation 0.93968	2.222 IU/mL Standard Deviation 1.5080
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 4 or 5	0.6438 IU/mL Standard Deviation 0.97767	2.633 IU/mL Standard Deviation 1.4955	2.377 IU/mL Standard Deviation 1.5934
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 6 or 7	0.1362 IU/mL Standard Deviation 0.095283	1.625 IU/mL Standard Deviation 1.0126	NA IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS Day 8 or 9	—	NA IU/mL Standard Deviation NA Mean and SD was not estimable for 1 participant.	—

SECONDARY outcome

Timeframe: Within 15 min pre-PEX and at multiple timepoints Post PEX at Days 2, 3, 4 or 5 and 6 or 7

Population: PK Set included all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value (ADAMTS-13 antigen and ADAMTS-13 activity). Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analysis at the specific time point.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=7 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS Day 2	0.1667 IU/mL Standard Deviation 0.17308	0.8493 IU/mL Standard Deviation 0.62139	0.9274 IU/mL Standard Deviation 0.93426
Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS Day 3	0.2579 IU/mL Standard Deviation 0.26836	1.110 IU/mL Standard Deviation 0.52612	1.174 IU/mL Standard Deviation 0.93910
Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS Day 4 or 5	0.3138 IU/mL Standard Deviation 0.38416	1.180 IU/mL Standard Deviation 0.65905	1.378 IU/mL Standard Deviation 1.1976
Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS Day 6 or 7	0.1660 IU/mL Standard Deviation 0.28752	1.070 IU/mL Standard Deviation 0.98879	NA IU/mL Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.

SECONDARY outcome

Timeframe: Pre-dose at Days 2, 3 4 or 5, 6 or 7, 8 or 9, and 11 or 12

Population: PK Set:all enrolled participants with confirmed aTTP diagnosis who received at least 1 dose of investigational product and who had at least 1 evaluable post-dose PK value.Overall number:particiapnts from PK set,included number of participants available for analysis.Number analyzed:number of participants available with ADAMTS activity absolute Ctrough values at given time point.Percentages are calculated based on total number of participants available for corresponding stratification per day.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=7 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 8 or 9	—	100.0 percentage of participants	—
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 11 or 12	—	100.0 percentage of participants	—
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 2	57.1 percentage of participants	100.0 percentage of participants	77.8 percentage of participants
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 3	57.1 percentage of participants	100.0 percentage of participants	85.7 percentage of participants
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 4 or 5	50.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With ADAMTS-13 Activity Trough Levels >10% Day 6 or 7	33.3 percentage of participants	66.7 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: From the start of study drug administration up to 6 months post remission

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Remission was defined as the time taken to achieve platelet count ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN 48 hours following initial normalization.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants Who Achieved Remission Following Normalization of Platelet Count	9 Participants	8 Participants	8 Participants

SECONDARY outcome

Timeframe: From the start of study drug administration up to 6 months post remission

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample. Overall number analyzed are the number of participants with data evaluable for analyses.

Remission was defined as a normal platelet count and LDH \<2 upper limit of normal (ULN) for at least 48 hours following initial normalization of platelet count (acute episode period). Normalization of platelet count was defined ≥150,000/μL, which was confirmed by a second normal platelet count ≥150,000/μL and LDH \<2 ULN.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants Achieving Remission	100.0 percentage of participants Interval 69.15 to 100.0	100.0 percentage of participants Interval 63.06 to 100.0	88.9 percentage of participants Interval 51.75 to 99.72

SECONDARY outcome

Timeframe: From start of study drug administration up to EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Exacerbation was defined as recurrent thrombocytopenia following a response and requiring a reinitiation of daily plasma exchange treatment after ≥1 day but ≤30 days of no plasma exchange treatment. Data is reported based on Kaplan-Meier estimates. Data was reported for time to first exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Time to First Exacerbation From Study Start up to 11 Months	NA days Interval 2.0 to The median and upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	8.0 days Interval 5.0 to The upper limit of CI was not estimable due to insufficient number of participants with events.
Time to First Exacerbation From 11 Months up to EOS (up to approximately 15 months)	NA days Interval 4.0 to The median and upper limit of CI was not estimable due to insufficient number of participants with events.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	NA days Interval 6.0 to The median and upper limit of CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From start of study drug administration up to EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for time to relapse in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Time to Relapse From Study Start up to 11 Months	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.
Time to Relapse From 11 Months up to EOS (up to approximately 15 months)	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.	NA days The median, lower and upper limit of CI was not evaluable due to no events in participants.

SECONDARY outcome

Timeframe: From start of study drug administration up to EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample. Overall number of participants analyzed are number of participants achieving remission. Number analyzed are the number of participants with data available for analyses at the given timepoint.

Exacerbation was determined by platelet count or the occurrence after remission of a major clinical event (e.g., myocardial infarction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants With Exacerbation From Study Start up to 11 Months	50.0 percentage of participants Interval 6.76 to 93.24	0.0 percentage of participants Interval 0.0 to 60.24	60.0 percentage of participants Interval 14.66 to 94.73
Percentage of Participants With Exacerbation From 11 Months up to EOS (up to approximately 15 months)	33.3 percentage of participants Interval 4.33 to 77.72	0.0 percentage of participants Interval 0.0 to 60.24	33.3 percentage of participants Interval 0.84 to 90.57

SECONDARY outcome

Timeframe: From start of study drug administration up to EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Relapse was determined by platelet count or the occurrence after remission of a major clinical event (e.g., Myocardial Infraction (MI), stroke, death) deemed by the investigator to be related to aTTP. Data was reported for percentage of participants with exacerbation in categories for participants enrolled before protocol amendment 4 (from study start up to 11 months) and after protocol amendment 4 (from 11 months up to the EOS).

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants With Relapse From Study Start up to 11 Months	0.0 percentage of participants Interval 0.0 to 60.24	0.0 percentage of participants Interval 0.0 to 60.24	0.0 percentage of participants Interval 0.0 to 52.18
Percentage of Participants With Relapse From 11 Months up to EOS (up to approximately 15 months)	0.0 percentage of participants Interval 0.0 to 45.93	0.0 percentage of participants Interval 0.0 to 60.24	0.0 percentage of participants Interval 0.0 to 70.76

SECONDARY outcome

Timeframe: From start of study drug administration up to EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Major clinical events related to TTP included Death, Stroke, MI and organ dysfunction not normalized within the 90-day observation period which consisted of chronic renal insufficiency, neurologic impairment and neurocognitive deficits.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) Renal Insufficiency	90.0 percentage of participants	100.0 percentage of participants	88.9 percentage of participants
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) Neurologic Deficits	60.0 percentage of participants	100.0 percentage of participants	77.8 percentage of participants
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) Brain Injury	50.0 percentage of participants	62.5 percentage of participants	66.7 percentage of participants
Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP) Death, Stroke and MI	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Major clinical events included clinically relevant bleeding (modified ITP score) or thrombosis at the site of line insertion, adverse reactions to plasma, including citrate reactions, allergic reactions, and transfusion-related acute lung injury (TRALI). Data is reported by summarizing the data for all parameters.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Major Clinical Events Related to PEX	6 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and EOS (at approximately Month 15)

Population: SAS included all participants randomized, who received any dose of investigational product. Overall number analyzed are the number of participants available for analyses. Number analyzed are the number of participants with data available for analysis at the specific time point.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline Baseline	7 Participants	8 Participants	8 Participants
Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline EOS at Month 15	3 Participants	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline and EOS (at approximately Month 15)

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Inhibitory Antibodies Relative to Baseline Baseline	6 Participants Interval 0.6 to 3.4	4 Participants Interval 1.0 to 1.8	7 Participants Interval 0.6 to 4.0
Number of Participants With Inhibitory Antibodies Relative to Baseline EOS at Month 15	3 Participants Interval 0.6 to 0.6	3 Participants Interval 0.7 to 1.7	2 Participants Interval 4.0 to 4.0

SECONDARY outcome

Timeframe: Up to 6 months

Population: Full Analysis Set (FAS) included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Percentages are based on the total number of participants per treatment group that have at least one ADA sample analyzed.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 ADA Positive: up to 3 Months	80.0 percentage of participants	62.5 percentage of participants	88.9 percentage of participants
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 ADA Positive: up to 6 Months	20.0 percentage of participants	75.0 percentage of participants	33.3 percentage of participants
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 Nab Positive: up to 3 Months	40.0 percentage of participants	37.5 percentage of participants	33.3 percentage of participants
Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655 Nab Positive: up to 6 Months	30.0 percentage of participants	37.5 percentage of participants	22.2 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product.

AE=any untoward medical occurrence in a participants administered IP that does not necessarily have a causal relationship with the treatment. TEAE=an adverse event with an onset that occurs after receiving study drug. SAE=an AE with any untoward clinical manifestation of signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, important medical event, bronchospasm associated with anaphylaxis, reviewed and confirmed seroconversion for human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), or parvovirus B19 (B19V). A product related AE is any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsens.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs Any TEAEs	10 Participants	9 Participants	8 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs Specifically Product-Related TEAEs	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs Serious TEAEs	4 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product.

Vital signs were assessed based on blood pressure, pulse rate, respiratory rate and body temperature.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Clinically Relevant Changes in Vital Signs	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product.

Clinical chemistry assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Clinically Relevant Changes in Clinical Chemistry	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: SAS included all participants randomized, who received any dose of investigational product.

Hematology consisted of complete blood count and leukocytes with differential (basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and platelet count.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Number of Participants With Clinically Relevant Changes in Hematology	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Rescue therapy was defined as any product with a known interruption to the pharmacokinetic/ pharmacodynamic (PK/PD) relationship between ADAMTS-13 activity, von Willebrand factor (VWF) activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence of receiving rescue therapy was assessed.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants Receiving Rescue Therapy	20.0 percentage of participants	0 percentage of participants	22.2 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until the EOS (up to approximately 15 months)

Population: FAS included all enrolled participants with confirmed aTTP diagnosis who were treated with a study product and had an ADAMTS-13 activity reading from at least one post infusion sample.

Rescue therapy was defined as any product with a known interruption to the PK/PD relationship between ADAMTS-13 activity, VWF activity, and platelet count. If rescue therapy was initiated, the administration of IP (SHP655 or placebo) was suspended for the duration of the study. Number of participants experiencing occurrence in meeting rescue therapy criteria was assessed. Percentage of participants with rescue therapy initiated are based on laboratory criteria and adverse events.

Outcome measures

Outcome measures
Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
Percentage of Participants Meeting Rescue Criteria	10.0 percentage of participants	0.0 percentage of participants	11.1 percentage of participants

Adverse Events

Placebo Post PEX + Placebo 12H Post PEX

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

SHP655 40 IU/kg Post PEX + Placebo 12H Post PEX

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

SHP655 40 IU/kg Post PEX + SHP655 40 IU/kg 12H Post PEX

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Post PEX + Placebo 12H Post PEX n=10 participants at risk Placebo Post PEX + Placebo 12H Post PEX	SHP655 40 IU/kg Post PEX + Placebo 12H Post PEX n=9 participants at risk SHP655 40 IU/kg Post PEX + Placebo 12H Post PEX	SHP655 40 IU/kg Post PEX + SHP655 40 IU/kg 12H Post PEX n=9 participants at risk SHP655 40 IU/kg Post PEX + SHP655 40 IU/kg 12H Post PEX
Hepatobiliary disorders Cholecystitis	0.00% 0/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.1% 1/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholelithiasis	10.0% 1/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Immune system disorders Drug hypersensitivity	10.0% 1/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	0.00% 0/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.1% 1/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	10.0% 1/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.1% 1/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	30.0% 3/10 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	22.2% 2/9 • From start of study drug administration up to end of the study (up to approximately 15 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER

Measure	Standard of Care (SoC) + Placebo n=10 Participants Participants received SoC daily plasma exchange (PEX) followed by placebo immediately and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 + Placebo n=8 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 international units per kilogram (IU/kg), IV injection, QD, immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).	SoC + SHP655 n=9 Participants Participants received SoC daily PEX and SHP655 40 +/- 4 IU/kg, IV injection, BID, immediately after PEX and 12 +/- 1 hours after completion of PEX until remission was achieved (up to approximately 6 months).
ADAMTS-13 Activity Levels FRETS: Day 1: ≤15 min Pre-PEX	0.1439 international units(IU)/ml Standard Deviation 0.19247	NA international units(IU)/ml Standard Deviation NA Mean and Standard Deviation (SD) was not evaluable as the samples were below the lower limit of quantitation (LLOQ).	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 1: ≤15 min Post-PEX	0.5418 international units(IU)/ml Standard Deviation 0.18345	0.5011 international units(IU)/ml Standard Deviation 0.19236	0.3029 international units(IU)/ml Standard Deviation 0.29020
ADAMTS-13 Activity Levels FRETS: Day 1: ≤15 min Post End of IP 1	0.4571 international units(IU)/ml Standard Deviation 0.19125	2.012 international units(IU)/ml Standard Deviation 0.82832	1.352 international units(IU)/ml Standard Deviation 0.93502
ADAMTS-13 Activity Levels FRETS: Day 1: 0.5-3 Hour (hr) Post End of IP 1	0.4420 international units(IU)/ml Standard Deviation 0.20895	1.905 international units(IU)/ml Standard Deviation 0.83349	1.266 international units(IU)/ml Standard Deviation 0.98904
ADAMTS-13 Activity Levels FRETS: Day 1: 4-6 hr Post End of IP 1	0.3197 international units(IU)/ml Standard Deviation 0.20545	1.163 international units(IU)/ml Standard Deviation 0.61343	0.7912 international units(IU)/ml Standard Deviation 0.69403
ADAMTS-13 Activity Levels FRETS: Day 1: ≤30 min Pre-IP 2	0.2108 international units(IU)/ml Standard Deviation 0.19731	1.027 international units(IU)/ml Standard Deviation 0.55951	0.4949 international units(IU)/ml Standard Deviation 0.54891
ADAMTS-13 Activity Levels FRETS: Day 1: ≤15 min Post End of IP 2	0.2267 international units(IU)/ml Standard Deviation 0.18660	1.022 international units(IU)/ml Standard Deviation 0.52060	1.545 international units(IU)/ml Standard Deviation 1.0854
ADAMTS-13 Activity Levels FRETS: Day 1: 0.5-3 hr Post End of IP 2	0.2007 international units(IU)/ml Standard Deviation 0.20012	1.015 international units(IU)/ml Standard Deviation 0.56462	1.300 international units(IU)/ml Standard Deviation 1.1114
ADAMTS-13 Activity Levels FRETS: Day 2: ≤15 min Pre-PEX	0.1691 international units(IU)/ml Standard Deviation 0.15909	0.7650 international units(IU)/ml Standard Deviation 0.61929	0.9482 international units(IU)/ml Standard Deviation 0.99771
ADAMTS-13 Activity Levels FRETS: Day 2: ≤15 min Post-PEX	0.5801 international units(IU)/ml Standard Deviation 0.16107	0.7808 international units(IU)/ml Standard Deviation 0.36544	0.8426 international units(IU)/ml Standard Deviation 0.54317
ADAMTS-13 Activity Levels FRETS: Day 2: ≤15 min Post End of IP 1	0.5433 international units(IU)/ml Standard Deviation 0.20267	1.965 international units(IU)/ml Standard Deviation 0.72122	1.977 international units(IU)/ml Standard Deviation 0.98427
ADAMTS-13 Activity Levels FRETS: Day 2: 0.5-3 hr Post End of IP 1	0.5281 international units(IU)/ml Standard Deviation 0.24842	2.105 international units(IU)/ml Standard Deviation 1.0656	2.153 international units(IU)/ml Standard Deviation 1.3856
ADAMTS-13 Activity Levels FRETS: Day 2: 4-6 hr Post End of IP 1	0.4170 international units(IU)/ml Standard Deviation 0.25202	1.622 international units(IU)/ml Standard Deviation 0.78046	1.411 international units(IU)/ml Standard Deviation 0.75100
ADAMTS-13 Activity Levels FRETS: Day 2: ≤30 min Pre-IP 2	0.3117 international units(IU)/ml Standard Deviation 0.24934	1.309 international units(IU)/ml Standard Deviation 0.48787	1.044 international units(IU)/ml Standard Deviation 0.55923
ADAMTS-13 Activity Levels FRETS: Day 2: ≤15 min Post End of IP 2	0.2998 international units(IU)/ml Standard Deviation 0.24960	1.283 international units(IU)/ml Standard Deviation 0.52550	1.960 international units(IU)/ml Standard Deviation 0.99952
ADAMTS-13 Activity Levels FRETS: Day 2: 0.5-3 hr Post End of IP 2	0.2833 international units(IU)/ml Standard Deviation 0.23999	1.398 international units(IU)/ml Standard Deviation 0.47591	2.129 international units(IU)/ml Standard Deviation 1.4547
ADAMTS-13 Activity Levels FRETS: Day 3: ≤15 min Pre-PEX	0.2468 international units(IU)/ml Standard Deviation 0.23669	1.044 international units(IU)/ml Standard Deviation 0.54178	1.129 international units(IU)/ml Standard Deviation 1.0570
ADAMTS-13 Activity Levels FRETS: Day 3: ≤15 min Post-PEX	0.5342 international units(IU)/ml Standard Deviation 0.22251	0.7786 international units(IU)/ml Standard Deviation 0.16455	0.7020 international units(IU)/ml Standard Deviation 0.40432
ADAMTS-13 Activity Levels FRETS: Day 3: ≤15 min Post End of IP 1	0.5215 international units(IU)/ml Standard Deviation 0.23522	2.210 international units(IU)/ml Standard Deviation 0.96057	1.911 international units(IU)/ml Standard Deviation 1.6633
ADAMTS-13 Activity Levels FRETS: Day 3: 0.5-3 hr Post End of IP 1	0.4970 international units(IU)/ml Standard Deviation 0.23979	2.086 international units(IU)/ml Standard Deviation 0.85567	1.785 international units(IU)/ml Standard Deviation 1.1566
ADAMTS-13 Activity Levels FRETS: Day 3: 4-6 hr Post End of IP 1	0.4670 international units(IU)/ml Standard Deviation 0.30646	1.680 international units(IU)/ml Standard Deviation 0.46457	1.271 international units(IU)/ml Standard Deviation 0.71567
ADAMTS-13 Activity Levels FRETS: Day 3: ≤30 min Pre-IP 2	0.3424 international units(IU)/ml Standard Deviation 0.29275	1.196 international units(IU)/ml Standard Deviation 0.44550	1.041 international units(IU)/ml Standard Deviation 0.84152
ADAMTS-13 Activity Levels FRETS: Day 3: ≤15 min Post End of IP 2	0.3514 international units(IU)/ml Standard Deviation 0.31264	1.263 international units(IU)/ml Standard Deviation 0.38468	1.478 international units(IU)/ml Standard Deviation 1.0343
ADAMTS-13 Activity Levels FRETS: Day 3: 0.5-3 hr Post End of IP 2	0.3227 international units(IU)/ml Standard Deviation 0.28191	1.267 international units(IU)/ml Standard Deviation 0.43580	1.902 international units(IU)/ml Standard Deviation 1.4522
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: ≤15 min Pre-PEX	0.2378 international units(IU)/ml Standard Deviation 0.30513	1.094 international units(IU)/ml Standard Deviation 0.67793	1.378 international units(IU)/ml Standard Deviation 1.1964
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: ≤15 min Post-PEX	0.4554 international units(IU)/ml Standard Deviation 0.26405	0.8222 international units(IU)/ml Standard Deviation 0.21072	0.8725 international units(IU)/ml Standard Deviation 0.57834
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: ≤15 min Post End of IP 1	0.7599 international units(IU)/ml Standard Deviation 1.0062	2.257 international units(IU)/ml Standard Deviation 0.95791	1.679 international units(IU)/ml Standard Deviation 1.3803
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 1	0.6699 international units(IU)/ml Standard Deviation 0.76875	2.425 international units(IU)/ml Standard Deviation 1.4869	1.405 international units(IU)/ml Standard Deviation 1.0118
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: 4-6 hr Post End of IP 1	0.5663 international units(IU)/ml Standard Deviation 0.69581	1.741 international units(IU)/ml Standard Deviation 0.84171	1.214 international units(IU)/ml Standard Deviation 1.0280
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: ≤30 min Pre-IP 2	0.5045 international units(IU)/ml Standard Deviation 0.60730	1.290 international units(IU)/ml Standard Deviation 0.64745	1.255 international units(IU)/ml Standard Deviation 0.98796
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: ≤15 min Post End of IP 2	0.4596 international units(IU)/ml Standard Deviation 0.58498	1.288 international units(IU)/ml Standard Deviation 0.63801	2.306 international units(IU)/ml Standard Deviation 1.6006
ADAMTS-13 Activity Levels FRETS: Day 4 or 5: 0.5-3 hr Post End of IP 2	0.4129 international units(IU)/ml Standard Deviation 0.49574	1.106 international units(IU)/ml Standard Deviation 0.59034	2.009 international units(IU)/ml Standard Deviation 1.4354
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: ≤15 min Pre-PEX	0.1246 international units(IU)/ml Standard Deviation 0.24910	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: ≤15 min Post-PEX	0.2587 international units(IU)/ml Standard Deviation 0.30131	0.7311 international units(IU)/ml Standard Deviation 0.48855	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: ≤15 min Post End of IP 1	0.2150 international units(IU)/ml Standard Deviation 0.26924	1.481 international units(IU)/ml Standard Deviation 0.89773	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 1	0.2194 international units(IU)/ml Standard Deviation 0.24929	1.673 international units(IU)/ml Standard Deviation 1.0721	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: 4-6 hr Post End of IP 1	0.1443 international units(IU)/ml Standard Deviation 0.24485	1.467 international units(IU)/ml Standard Deviation 1.1232	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: ≤30 min Pre-IP 2	0.1272 international units(IU)/ml Standard Deviation 0.25440	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: ≤15 Minutes Post End of IP 2	0.1422 international units(IU)/ml Standard Deviation 0.28435	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.
ADAMTS-13 Activity Levels FRETS: Day 6 or 7: 0.5-3 hr Post End of IP 2	0.1336 international units(IU)/ml Standard Deviation 0.26710	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: ≤15 min Pre-PEX	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: ≤15 min Post-PEX	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not evaluable as the samples were below LLOQ.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: ≤15 min Post End of IP 1	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: 0.5-3 hr Post End of IP 1	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: 4-6 hr Post End of IP 1	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: ≤30 Minutes Pre-IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: ≤15 min Post End of IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 8 or 9: 0.5-3 hr Post End of IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 11 or 12: ≤15 min Pre-PEX	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 11 or 12: ≤15 min Post-PEX	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 11 or 12: ≤30 min Pre-IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 11 or 12: ≤15 min Post End of IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—
ADAMTS-13 Activity Levels FRETS: Day 11 or 12: 0.5-3 hr Post End of IP 2	—	NA international units(IU)/ml Standard Deviation NA Mean and SD was not estimable for 1 participant.	—