phase 1 dose escalation, single dose study to assess safety and pharmacokinetics of bax930 in hereditary thrombotic thrombocytopenic purpura (ttp)

Conditions: Hereditary Thrombotic Thrombocytopenic Purpura (TTP)

Summary: 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.


Eligibility criteria:
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.