severe congenital thrombotic thrombocytopenic purpura (cTTP, Upshaw-Schulman Syndrome [USS], hereditary thrombotic thrombocytopenic purpura [hTTP]) MedDRA version: 20.0 Level: LLT Classification code 10043562 Term: Thrombocytopenic purpura, thrombotic System Organ Class: 100000004851
Conditions
Interventions
Product Name: Recombinant A Disintegrin and Metalloproteinase with Thrombospondin Type-1 Motifs 13
Product Code: BAX930 or SHP655
Pharmaceutical Form: Powder and solvent for solution for injection
INN
Sponsors
Baxalta Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject or legally authorized representative has provided signed informed consent (=18 years of age) and/or assent form (signed by legal representative if subject is 2×ULN) at screening. Subjects presenting with minor, but stable laboratory abnormalities at the time of screening may be enrolled (prophylactic cohort only). 5. Subject is currently on a prophylactic dosing regimen or has a documented history of at least 1 TTP event and an ability to tolerate SoC prophylactic dosing (prophylactic cohort only). 6. Subjects =16 years of age must have a Karnofsky score =70% and subjects =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including acquired TTP. 2. Subject has known hypersensitivity to hamster proteins. 3. Subject has experienced an acute TTP episode less than 30 days prior to screening (prophylactic cohort only). 4. Subject has a medical history or presence of a functional ADAMTS13 inhibitor at screening. 5. 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 (HIV)-positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who are receiving chronic immunosuppressive drugs. 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 (ALT) =2xULN b. Severe hypoalbuminemia <24 g/L c. Portal vein hypertension (e.g., 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 (e.g., ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of FFP to prevent allergic manifestations is permitted. 11. Subject has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylaxis 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 less than 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 enrolment. 19. Any contraindication to standard of care medicinal product(s) as per local prescribing information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine the incidence of acute TTP episodes in subjects with severe cTTP receiving either standard of care (SoC) or BAX 930 as a prophylactic treatment;Secondary Objective: 1. To evaluate the efficacy of BAX 930 in the treatment of acute TTP episodes as measured by the 1) number of acute TTP events responding to treatment and 2) time to resolution in both the prophylactic and the on-demand cohorts 2. To evaluate the safety and tolerability of BAX 930 in terms of related AEs and SAEs in both the prophylactic and the on-demand cohorts 3. To evaluate the pharmacokinetics (PK) of ADAMTS13 for up to 288 hours post-infusion in each treatment arm (BAX 930 and SoC) in the prophylactic cohort 4. 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 5. To assess the immunogenicity of BAX 930 as measured by the incidence of binding and inhibitory antibodies to ADAMTS13 in both the prophylactic and the on-demand cohorts. for full information on objectives reference is made to the protocol.;Primary end point(s): 1. Incidence of acute TTP episodes among subjects receiving either BAX 930 or SoC prophylactically during the corresponding treatment periods;Timepoint(s) of evaluation of this end point: Interim analysis performed after all adult subjects complete Period 3 in the prophylaxis cohort and at the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy 1. Number and incidence of acute TTP episodes responding to BAX 930, defined as not requiring the use of another ADAMTS13 containing agent 2. Time to resolution of clinical symptomatology, if present, and normalization of laboratory parameters (platelet count =150,000/µL; LDH =1.5×ULN) following initiation of treatment in acute TTP episodes with BAX 930 or SoC agent 3. Incidence of thrombocytopenia defined as a drop in platelet count =25% of baseline or a platelet count 1.5×ULN 5. Incidence of neurological symptoms (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures) 6. Incidence of renal dysfunction defined as an increase in serum creatinine >1.5×baseline 7. Incidence of abdominal pain 8. Incidence of supplemental doses prompted by subacute manifestations 9. Incidence of dose modification not prompted by an acute event 10. Incidence of acute TTP episodes while subjects are on their final dose and dosing regimen Safety/Immunogenicity 1. Incidence of product-related and unrelated AEs and SAEs during each treatment period 2. Incidence of binding and inhibitory antibodies to ADAMTS13 3. Clinically relevant changes in vital signs, clinical chemistry, and hematology 4. Estimated total quantity of ADAMTS13 administered during the treatment of acute events Pharmacokinetics/Pharmacodynamics 1. Assessment of the PK parameters (incremental recovery [IR], area under the plasma curve [AUC], terminal half-life [t1/2], mean residence time [MRT], systemic clearance [CL], steady state volume of distribution [Vss], and maximum concentration following infusion [Cmax]) for ADMATS13 activity and ADMATS13 antigen for both the SoC agent and BAX 930 2. Assessment of PD markers, including VWF:Ag, VWF:RCo, and VWF multimer pattern at baseline and following infusion of the SoC agent and BAX 930 treatment during the initial PK assessment 3. Assessment of ADAMTS13 activity (trough levels) and VWF parameters prior to e | — |
Countries
Austria, Canada, France, Germany, Italy, Japan, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactArchana Salva
Baxalta Innovation GmbH
Outcome results
None listed