Study of rADAMTS-13 (SHP655) in the Treatment of Particip... | NCT03922308

ID	Type	Description	Link
2018-003775-35	EudraCT Number

Name	Class
Takeda Development Center Americas, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Standard of Care (SoC) + Placebo	Placebo Comparator	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).	Other: Placebo Other: Standard of Care
SoC + SHP655 + Placebo	Experimental	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).	Other: Placebo Drug: SHP655 Other: Standard of Care
SoC + SHP655	Experimental	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).	Drug: SHP655 Other: Standard of Care

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Other	Participants will receive injection of placebo matched to SHP655.	SoC + SHP655 + Placebo Standard of Care (SoC) + Placebo

Measure	Description	Time Frame
ADAMTS-13 Activity Levels	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).	Up to Days 11 or 12
Platelet Count	The platelet counts are reported in units of 10^9 per liter blood.	Baseline and end of study (EOS) (up to approximately 15 months)
Lactate Dehydrogenase (LDH) Levels	The lactate dehydrogenase levels are reported.	Baseline and EOS (up to approximately 15 months)

Measure	Description	Time Frame
Dose(s) of SHP655 Needed to Achieve and Maintain Adequate Plasma Levels of rADAMTS-13	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.	From start of study drug administration up to 13 weeks (following remission up to 6 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant or legally authorized representative voluntarily signs informed consent. For participants unable to provide consent, a fully recognized medical proxy may be used according to local laws.
Participant is 18 to 75 years old at the time of screening.
Participant has been diagnosed with primary or secondary autoimmune acquired thrombotic thrombocytopenic purpura (aTTP) based on the following criteria:

a) Thrombocytopenia [drop in platelet count >=50% or platelet count <100,000/microlitre (μL)] i) No more than 3 participants per arm may be enrolled with a screening platelet count >= 50,000/μL.

b) Microangiopathic hemolytic anemia [elevation of lactate dehydrogenase (LDH) >2-fold or by presence or increase of schistocytes in peripheral blood smear].
Willingness to fully comply with study procedures and requirements, and intention to initiate plasma exchange (PEX). Participants may be provisionally entered into the trial and undergo randomization pending the results of the ADAMTS-13 activity, anti-ADAMTS-13 antibody, and genetic testing for congenital thrombotic thrombocytopenic purpura (cTTP).
If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered.

Exclusion Criteria:

Participant has been diagnosed with congenital TTP.
Participant has plasma ADAMTS-13 activity > 10% of normal at the central lab; if screening samples are not taken until after the first PEX, ADAMTS-13 activity from the local lab is permitted to determine eligibility.
Participant has been diagnosed with another cause of thrombotic microangiopathy (TMA) including: DIC, disseminated malignancy, malignant hypertension, hematopoietic stem cell transplantation, shiga toxin related and atypical HUS, drug toxicity (e.g. gemcitabine, mitomycin C, clopidogrel) and pregnancy-related thrombocytopenia syndromes (e.g. HELLP, eclampsia).
Participant has been exposed to another IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving IP or investigational device during the course of the study.
Participant has received caplacizumab within 1 month prior to study enrollment.
Participant is human immunodeficiency virus positive (HIV+) with unstable disease or CD4+ count <=200 cells/mm^3 within 3 months screening.
Participants with conditions of severe immunodeficiency.
Participant has had a previous aTTP event in the past 30 days.
Participant has another underlying progressive fatal disease and/or life expectancy of less than 3 months.
Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures
Participant suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude. However, a fully recognized medical proxy will be permitted to provide consent.
If female, participant is pregnant or lactating.
Participant is a family member or employee of the Sponsor or investigator.
Any contraindication to PEX, methylprednisolone and/or rituximab as per prescribing information.
Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of SHP655.

Name	Affiliation	Role
Study Director	Shire	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The University of Alabama at Birmingham		Birmingham	Alabama	35249	United States
Brigham and Women's Hospital

Label	URL
To obtain more information on the study, click here/on this link	View source

ID	Title	Description
FG000	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).
FG001	SoC + SHP655 + Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Original	Oct 3, 2018	Jul 22, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

ADAMTS-13 Activity Levels

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).

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.

Posted

Mean

Standard Deviation

international units(IU)/ml

Up to Days 11 or 12

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Units	Counts
Participants	OG00010 OG0018 OG0029

Title

Denominators

Categories

FRETS: Day 1: ≤15 min Pre-PEX

- ParticipantsOG0008
- ParticipantsOG0017
- ParticipantsOG0028

Title	Measurements

Primary

Platelet Count

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

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.

Posted

Mean

Standard Deviation

10^9 platelets/L

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Primary

Lactate Dehydrogenase (LDH) Levels

The lactate dehydrogenase levels are reported.

Posted

Mean

Standard Deviation

international units (IU)/L

Baseline and EOS (up to approximately 15 months)

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Dose(s) of SHP655 Needed to Achieve and Maintain Adequate Plasma Levels of rADAMTS-13

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.

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

Posted

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

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

PK/PD Temporal Relationship of Safety and Efficacy Parameter as a Function of ADAMTS-13 Activity

Parameters included platelet and LDH counts.

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

Posted

Up to 6 months

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Number of Participants With ADAMTS-13 Binding Antibodies Per Titer

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.

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.

Posted

Count of Participants

Participants

Baseline and EOS (up to approximately 15 months)

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 international 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).
OG002	SoC + SHP655

Secondary

Inhibitory Autoantibodies (Nab) Titer Levels

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).

Posted

Median

Full Range

BU/mL

Baseline and EOS (up to approximately 15 months)

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

ADAMTS-13 Activity Levels in Participants Receiving Additional SHP655 for up to 30 Days After Resolution by Using FRETS

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).

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.

Posted

Mean

Standard Deviation

IU/mL

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

ID	Title	Description
OG000	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).
OG001	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).

Secondary

Relationship Between ADAMTS-13 Activity and End-organ Disease Status

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

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

Posted

Up to 6 months

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Predose Concentration (Cpre) to Maximum Plasma Concentration (Cmax) Ratio

Posted

Mean

Standard Deviation

ratio

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

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

AUC Overall: Area Under the Plasma Concentration Time Curve ADAMTS13 Activity by Using FRETS

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.

Posted

Mean

Standard Deviation

h*IU/mL

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Systemic and Antibody Induced Clearance

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

Posted

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)

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Cmax: Maximum ADAMTS-13 Activity Between PEX or SHP655 Infusions by Using FRETS

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.

Posted

Mean

Standard Deviation

IU/mL

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

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Trough Levels of ADAMTS-13 Prior PEX ADAMTS13 Activity by Using FRETS

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.

Posted

Mean

Standard Deviation

IU/mL

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Percentage of Participants With ADAMTS-13 Activity Trough Levels >10%

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants Who Achieved Remission Following Normalization of Platelet Count

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Percentage of Participants Achieving Remission

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	SoC + SHP655

Secondary

Time to First Exacerbation

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).

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.

Posted

Median

50% Confidence Interval

days

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	SoC + SHP655

Secondary

Time to Relapse

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).

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.

Posted

Median

50% Confidence Interval

days

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

ID	Title	Description
OG000	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).
OG001	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).
OG002	SoC + SHP655

Secondary

Percentage of Participants With Exacerbation

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).

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).

Secondary

Percentage of Participants With Relapse

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).

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	SoC + SHP655

Secondary

Percentage of Participants With Major Clinical Events Related to Thrombotic Thrombocytopenic Purpura (TTP)

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.

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants With Major Clinical Events Related to PEX

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.

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.

Posted

Count of Participants

Participants

Up to 6 months

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants With Anti-drug Antibody (ADA) Titer of Binding Relative to Baseline

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.

Posted

Count of Participants

Participants

Baseline and EOS (at approximately Month 15)

ID	Title	Description
OG000	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).
OG001	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).
OG002	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).

Secondary

Number of Participants With Inhibitory Antibodies Relative to Baseline

Posted

Count of Participants

Participants

Baseline and EOS (at approximately Month 15)

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Percentage of Participants With at Least One Positive Identification of Antibodies to SHP655

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

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.

Posted

Number

percentage of participants

Up to 6 months

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Specifically Product-Related TEAEs and Serious TEAEs

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo

Secondary

Number of Participants With Clinically Relevant Changes in Vital Signs

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

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants With Clinically Relevant Changes in Clinical Chemistry

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

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Number of Participants With Clinically Relevant Changes in Hematology

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	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).

Secondary

Percentage of Participants Receiving Rescue Therapy

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.

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002	SoC + SHP655

Secondary

Percentage of Participants Meeting Rescue Criteria

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.

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	Standard of Care (SoC) + Placebo	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).
OG001	SoC + SHP655 + Placebo	Participants received SoC daily PEX and SHP655 40 +/- 4 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).
OG002

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Abnormal weight gain	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0012 affected9 at risk EG0021 affected9 at risk
Anal injury	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Anxiety	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0021 affected9 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Autonomic nervous system imbalance	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Blood creatinine increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Blood glucose increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Blood pressure increased	Investigations	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Bradycardia	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Catheter site bruise	General disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Catheter site pain	General disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Catheter site related reaction	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Chest discomfort	General disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Chest pain	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Citrate toxicity	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Confusional state	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Constipation	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0013 affected9 at risk EG0021 affected9 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Delirium	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Depressed mood	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0012 affected9 at risk EG0020 affected9 at risk
Dizziness	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0003 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Dysuria	Renal and urinary disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Extrasystoles	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Eye pain	Eye disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Fatigue	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Feeling abnormal	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Feeling cold	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Flushing	Vascular disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Gastroenteritis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Headache	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0011 affected9 at risk EG0021 affected9 at risk
Heart rate increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0012 affected9 at risk EG0020 affected9 at risk
Hot flush	Vascular disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Hyperlactacidaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Hypertension	Vascular disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0021 affected9 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0012 affected9 at risk EG0020 affected9 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Insomnia	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Lymphocyte count decreased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Medical device site discomfort	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Nasopharyngitis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Nausea	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0003 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Neutrophil count increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Neutrophilia	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Non-cardiac chest pain	General disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Oral herpes	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Orthopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Oxygen saturation decreased	Investigations	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Palpitations	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Panic attack	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Papule	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Paraesthesia	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0012 affected9 at risk EG0020 affected9 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Peripheral swelling	General disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Procedural anxiety	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0003 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Pyrexia	General disorders	MedDRA 24	Systematic Assessment	EG0003 affected10 at risk EG0011 affected9 at risk EG0021 affected9 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0021 affected9 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Restlessness	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Sensory disturbance	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Skin tightness	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Skin weeping	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Suffocation feeling	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Swelling face	General disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Syncope	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Taste disorder	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Tooth infection	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Transfusion related complication	Injury, poisoning and procedural complications	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Tremor	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Vision blurred	Eye disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Weight decreased	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
White blood cell count abnormal	Investigations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Post PEX + Placebo 12H Post PEX	Placebo Post PEX + Placebo 12H Post PEX	10	4	10	10	10
EG001	SHP655 40 IU/kg Post PEX + Placebo 12H Post PEX	SHP655 40 IU/kg Post PEX + Placebo 12H Post PEX	9	1	9	9	9
EG002	SHP655 40 IU/kg Post PEX + SHP655 40 IU/kg 12H Post PEX	SHP655 40 IU/kg Post PEX + SHP655 40 IU/kg 12H Post PEX	9	3	9	6	9

ID	Term
D011696	Purpura, Thrombocytopenic
D011693	Purpura
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D057049	Thrombotic Microangiopathies
D013921	Thrombocytopenia
D001791	Blood Platelet Disorders
D000095542	Cytopenia
D019851	Thrombophilia
D006470	Hemorrhage
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D012877	Skin Manifestations
D012816	Signs and Symptoms

ID	Term
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation

ID	Title	Description
BG000	Standard of Care (SoC) + Placebo	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).
BG001	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).
BG002	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).
BG003	Total	Total of all reporting groups

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cholecystitis	Hepatobiliary disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Pneumonia	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected9 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected9 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected9 at risk
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0003 affected10 at risk EG0010 affected9 at risk EG0022 affected9 at risk