Phase 1 Dose Escalation, Single Dose Study to Assess Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
Phase 1 Dose Escalation, Single Dose Study to Assess Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
The purpose of this Phase 1, prospective, uncontrolled, open-label, multicenter,
 dose-escalation study is to evaluate the safety, including immunogenicity, and
 pharmacokinetics of BAX930 (rADAMTS13) in a total of 14 evaluable subjects diagnosed with
 severe hereditary thrombotic thrombocytopenic purpura (TTP) (plasma ADAMTS13 activity <6%)
 who are assigned to one of three dose cohorts.
Inclusion Criteria:

 -  Subject is between 12 and 65 years of age, inclusive. (The first 2 subjects in any
 cohort will be ≥ 18 years of age.)

 -  Subject and/or legally authorized representative has provided written informed
 consent.

 -  Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined
 as 1) confirmed by genetic testing, documented in patient history or at screening, and
 2) ADAMTS13 activity < 6%, documented in patient history or at screening. NOTE: In
 patients receiving prophylactic therapy with fresh frozen plasma (FFP) or other
 ADAMTS13 containing products, the levels of plasma ADAMTS13 activity may exceed 6% at
 screening.

 -  Cryoprecipitate, FFP, or other ADAMTS13 containing products interfering with ADAMTS13
 PK have to be paused at least 10 days prior to infusion of the investigational
 product.

 -  The subject is not displaying any severe TTP symptoms at screening. Patients
 presenting with minor, but stable laboratory abnormalities (LDH not higher than 3
 times the upper limit of normal; platelet count not lower than 100,000 per μl) at
 screening may be enrolled.

 -  Subjects ≥18 years of age have a Karnofsky score ≥ 60%, and subjects < 18 years of age
 have a Lansky score ≥ 70%.

 -  Subject is hepatitis C virus negative (HCV-) as confirmed by antibody or polymerase
 chain reaction (PCR) testing; HCV positive (HCV+) subjects are eligible for inclusion
 if their disease is chronic but stable.

 -  If female of childbearing potential, subject presents with a negative serum pregnancy
 test and agrees to employ adequate birth control measures for the duration of the
 study.

 -  Subject is willing and able to comply with the requirements of the protocol.

 Exclusion Criteria:

 -  Subject has been diagnosed with any other TTP-like disorder (for example,
 microangiopathic hemolytic anemia), including acquired TTP.

 -  Subject has known hypersensitivity to hamster proteins or other components of the
 investigational product.

 -  Subject has a medical history or presence of a functional neutralizing ADAMTS13
 inhibitor at screening.

 -  Subject has a medical history of immunological disorders, excluding seasonal allergic
 rhinitis/conjunctivitis/mild asthma, food allergies or animal allergies.

 -  Subject has a medical history of hematological disorders, in particular systemic lupus
 erythematosus, amyloidosis, antiphospholipid antibody syndrome, vasculitis, other
 hemolytic anemia, disseminated intravascular coagulation, and systemic scleroderma.

 -  Subject has a history of significant neurological events, such as major stroke,
 indicating that a relapse might have severe consequences, as judged by the
 investigator.

 -  Subject is HIV positive with an absolute CD4 count < 200/mm3.

 -  Subject has been diagnosed with a cardiovascular disease [New York Heart Association
 (NYHA) classes 3-4].

 -  Subject is scheduled to undergo elective surgery during study participation.

 -  Subject has been diagnosed with severe liver disease, as evidenced by, but not limited
 to, any of the following: serum ALT 3 times the upper limit of normal, international
 normalized ratio (INR) > 1.5, hypoalbuminemia, portal vein hypertension (e.g. presence
 of otherwise unexplained splenomegaly, history of esophageal varices).

 -  Subject has been diagnosed with severe glomerular disease, with gross proteinuria and
 a serum creatinine level ≥ 2.5 mg/dL.

 -  Subject has been treated with an immunomodulatory drug, in case of corticoids with an
 equivalent to hydrocortisone greater than 10 mg /day, excluding topical treatment
 (e.g. ointments, nasal spray), within 30 days prior to enrollment.

 -  Subject has a history of drug and/or alcohol abuse within the last 6 months prior to
 study enrollment.

 -  Subject has a life expectancy of less than 3 months.

 -  Subject is identified by the investigator as being unable or unwilling to cooperate
 with study procedures.

 -  Subject is a family member or employee of the investigator.

 -  Subject 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.

 -  If female, subject is pregnant or lactating at the time of study enrollment.

 -  Subject has participated in another clinical study involving an investigational
 product or device within 30 days prior to study enrollment.

 -  Subject is scheduled to participate in another clinical study involving an
 investigational product or device during the course of this study.