Hereditary Thrombotic Thrombocytopenic Purpura (TTP) Clinical Trial
Official title:
BAX930 (rADAMTS13): A Phase 1 Prospective, Uncontrolled, Open-Label, Multicenter, Dose-Escalation Study Evaluating the Safety and Pharmacokinetics in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
| Verified date | May 2021 |
| Source | Takeda |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 16 |
| Est. completion date | February 22, 2016 |
| Est. primary completion date | February 22, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 12 Years to 65 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Austria | General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien) | Vienna | |
| Germany | Universitätsklinikum Hamburg-Eppendorf | Hamburg | |
| Germany | Universitätsklinikum Jena | Jena | |
| Japan | • Tokyo Medical and Dental University Hospital, Faculty of Medicine | Bunkyo-ku, Tokyo | |
| Japan | Hyogo College of Medicine Hospital, Department of Hematology | Nishinomiya-shi | |
| Poland | Institute of Hematology and Transfusion Medicine | Warsaw | |
| Switzerland | Inselspital - Universitaetsspital Bern | Bern | |
| United Kingdom | University College London Hospital NHS Foundation Trust | London | |
| United States | Ohio State University Medical Center | Dublin | Ohio |
| United States | The Methodist Hospital Research Institute | Houston | Texas |
| United States | Oregon Health & Science University | Portland | Oregon |
| Lead Sponsor | Collaborator |
|---|---|
| Baxalta now part of Shire |
United States, Austria, Germany, Japan, Poland, Switzerland, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation | Up to 28 (± 3) days after investigational product infusion | ||
| Secondary | Pharmacokinetic [PK] parameter 'incremental recovery [IR]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'maximum concentration following infusion [Cmax]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'minimum time to reach Cmax [T max]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'terminal or disposition half-life [T1/2]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'mean residence time [MRT]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'systemic clearance [Cl]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'area under the plasma/time curve [AUC]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | PK parameter 'steady state volume of distribution [Vss]' | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion | |
| Secondary | Plasma von Willebrand factor: Ristocetin cofactor activity [VWF:RCo], von Willebrand factor antigen [VWF:Ag] and VWF structure analysis | Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3 | Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion |