Study of rADAMTS-13 (SHP655) in the Treatment of Participants With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
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.
- Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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 greater than or equal to (>=) 50% or platelet count lesser than (<) 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) greater than (>) 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.
- 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 lesser than or equal to (<=) 200 cells/mm3 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.
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Double (Participant, Investigator)
Standard of Care (SoC) + Placebo Twice Daily
|Participants will receive SoC daily plasma exchange (PEX) immediately followed by placebo (0.9% saline) and after 12 +/- 1 hours until remission is achieved.||
SoC + SHP655 Once Daily + Placebo 12 Hours Later
|Participants will receive SoC daily PEX and intravenous (i.v.) injection of 40 +/- 4 International units per kilogram (IU/kg) of SHP655 once daily immediately after PEX and placebo 12 +/- 1 hours after completion of PEX until remission is achieved.||
SoC + SHP655 Twice Daily
|Participants will receive SoC daily plasma exchange and i.v. injection of 40 +/- 4 IU/kg of SHP655 twice daily (BID) immediately after PEX and 12 +/- 1 hours after completion of PEX until remission is achieved.||
Study ContactShire Contact
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