Phase 1 Dose Escalation, Single Dose Study to Assess Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)

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.