Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Condition: Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
Intervention: Placebo; SHP655; Standard of Care
Intervention description: Participants will receive injection of placebo matched to SHP655.; Participants will receive injection of SHP655.; Participants will receive PEX as Standard of Care (SOC).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the pharmacokinetics, safety, and efficacy of
      rADAMTS-13 (SHP655) administered in addition to standard of care (SoC) treatment of acquired
      thrombotic thrombocytopenic purpura (aTTP) participants.
    

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.