congenital Thrombotic thrombocytopenic purpura (TTP)
Conditions
Interventions
Product Name: Recombinant A Disintegrin and Metalloproteinase Thrombospondin Type-1 Motifs 13
Product Code: TAK-755 or BAX930 or SHP655
Pharmaceutical Form: Powder and solvent for solution for injecti
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who have completed TAK-755 Phase 3 pivotal study (281102) and who meet ALL of the following criteria are eligible for this study: 1. Subject or legally authorized representative has provided signed informed consent (=18 years of age) and/or assent form (2 × upper limit of normal [ULN]) at screening (prophylactic cohort only). 5. Subjects =16 years of age must have a Karnofsky score =70% and subjects 2 × ULN) at screening (prophylactic cohort only). 7. Subjects =16 years of age must have a Karnofsky score =70% and subjects <16 years of age must have a Lansky score =80%. 8. Subject is hepatitis C virus negative (HCV) as confirmed by antibody or polymerase chain reaction testing OR HCV positive (HCV+) if their disease is chronic but stable. 9. If female of childbearing potential, subject presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the dur
Exclusion criteria
Exclusion criteria: The subject will be excluded from the study if any of the following exclusion criteria are met. For both subjects who have completed TAK-755 Phase 3 pivotal study (281102) and TAK 755 naïve subjects: 1. Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including immune-mediated TTP. 2. Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of TAK-755. 3. Subject has a medical history or presence of a functional ADAMTS-13 inhibitor at screening. 4. Subject has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including subjects who are human immunodeficiency virus positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who are receiving chronic immunosuppressive drugs. 5. 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. 6. Subject has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4). 7. Subject with end stage renal disease requiring chronic dialysis. 8. Subject has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following: a. Serum alanine aminotransferase =2 × ULN b. Severe hypoalbuminemia <24 g/L c. Portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices). 9. In the opinion of the investigator, the subject has another clinically significant concomitant disease that may pose additional risks for the subject. 10. Subject has been treated with an immunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma to prevent allergic manifestations is permitted. 11. Subject has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylactic cohort only). 12. Subject is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment. 13. Subject has a history of drug and/or alcohol abuse within the last 2 years. 14. Subject has a progressive fatal disease and/or life expectancy of =3 months. 15. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures 16. 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. 17. Subject is a family member or employee of the sponsor or investigator. 18. If female, subject is pregnant or lactating at the time of enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of TAK-755 (rADAMTS-13) in terms of related adverse events (AEs) and serious adverse events (SAEs) in both the prophylactic and the on-demand cohorts.;Secondary Objective: 1. To evaluate the efficacy of TAK-755 in the treatment of acute thrombotic thrombocytopenic purpura (TTP) episodes as measured by the a) number of acute TTP events responding to treatment and b) time to resolution of the acute TTP in either the prophylactic or the on-demand cohorts. 2. To evaluate the incidence of isolated TTP manifestations including thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction, neurologic signs and symptoms, and abdominal pain in the prophylactic cohort. 3. To evaluate the proportion of subjects that require dose modification and supplemental dose in the prophylactic cohort. 4. To evaluate the incidence of subacute manifestations in subjects receiving prophylactic treatment. For more secondery objectives please refer to Protocol pages 10,11.;Primary end point(s): There is no primary efficacy endpoint for this study, as the primary objective of the study is long-term safety.;Timepoint(s) of evaluation of this end point: Various timepoints throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Prophylactic cohort: Efficacy analysis for the prophylactic cohort will provide the number and incidence rate of acute TTP events in total and by enrollment status (“Naïve” or having completed the Phase 3 pivotal study [281102]), with the corresponding 95%, 2-sided confidence intervals (CIs). 2. Prophylactic and on-demand cohorts: For acute TTP events, the number and proportion of acute events responding to treatment will be summarized, along with the 2-sided 95% CIs for the pooled prophylactic and on-demand cohort data as well as by cohort. ;Timepoint(s) of evaluation of this end point: Various timepoints throughout the study | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Russian Federation, Serbia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactEmily Skelton
Baxalta US Inc.
Outcome results
None listed