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

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 = 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.