Acquired thrombotic thrombocytopenic purpura (TTP) MedDRA version: 16.0 Level: PT Classification code 10043648 Term: Thrombotic thrombocytopenic purpura System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Anti-von Willebrand Factor Nanobody, INN = Caplacizumab
Product Code: ALX-0081
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Caplacizumab
CAS Number: 915810- 67-2
Curr
Sponsors
Ablynx
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years of age or older (adults) or aged 12 to =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Platelet count greater or equal to 100,000/µL 2. Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) 3. Clinical evidence of enteric infection with E. coli 0157 or related organism 4. Anti-phospholipid syndrome 5. Diagnosis of disseminated intravascular coagulation (DIC) 6. Pregnancy or breast-feeding 7. Haematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy 8. Known congenital TTP 9. Active bleeding or high risk of bleeding 10. Uncontrolled arterial hypertension 11. Known chronic treatment with anticoagulant treatment that can not be stopped safely, including but not limited to: •vitamin K antagonists •heparin or low molecular weight heparin (LMWH) •non-acetyl salicylic acid non-steroidal anti-inflammatory molecules 12. Severe or life threatening clinical condition other than TTP that would impair participation in the trial 13. Subjects with malignancies resulting in a life expectation of less than 3 months 14. Subjects with known or suspected bone marrow carcinosis 15. Subjects who cannot comply with study protocol requirements and procedures. 16. Known hypersensitivity to the active substance or to excipients of the study drug 17. Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows: •bilirubin > 3 x ULN •alanine aminotransferase/aspartate aminotransferase (ALT/AST) > 5 x ULN •alkaline phosphatase (AP) > 5 x ULN •gamma glutamyl transpeptidase (GGT) > 5 x ULN 18. Severe chronic renal impairment, as defined by GFR < 30 mL/min
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Reduction of time-to-response, defined by the achievement of laboratory blood marker response, confirmed at 48 hours after the initial reporting of this response;Secondary Objective: •Improvement in number of subjects responding to therapy •Reduction PE procedure-related items •Reduction time to resolution or improvement of signs and symptoms typical of TTP, incl. blood markers •Reduction of number of exacerbations (defined as recurrent thrombocytopenia following a response and requiring a re-initiation of daily PE treatment after = 1 day but = 30 days after last daily PE) and relapses (defined as de novo event of TTP occurring later than 30 days after last daily PE) •Improvement of cognitive level at steady state post acute phase (adults only) •Improvement of clinical symptoms and organ function •Reduction in mortality within PE treatment period and within subsequent study drug treatment period (incl. tapering) •Reduction of concomitant treatment-related complications •Safety and immunogenicity evaluation of adjunctive treatment with ALX-0081 •Determination of pharmacokinetic and pharmacodynamic characteristics of ALX 0081 in patients with acquired TTP;Primary end point(s): Time-to-response, based on the following criteria: - Recovery of platelets = 150,000/µL - This response must be confirmed at 48 hours after the initial reporting of platelet recovery equal to or above 150,000/µL by a de novo measure of platelets = 150,000/µL and lactate dehydrogenase (LDH) = 2 X upper limit of normal (ULN) (i.e. “confirmed platelet response”) ;Timepoint(s) of evaluation of this end point: - initial timepoint: time when platelets have recovered to = 150,000/µL - this is to be confirmed at 48 hrs after initial timepoint | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Number of subjects with complete remission (defined as confirmed platelet response and absence of exacerbation) • Number of (subjects with) exacerbations of TTP (defined as recurrent thrombocytopenia following a confirmed platelet response and requiring a re-initiation of daily PE treatment after = 1 day but = 30 days after the last daily PE) and time to first exacerbation of TTP • Number of subjects relapsing of TTP (defined as de novo event of TTP that occurs later than 30 days after the last daily PE) • Number of daily PE sessions, number of plasma units administered and number of days of daily PE • Resolution of non-focal neurological symptoms as defined by neurocognitive function at complete remission, measured by a neurocognitive test battery (adults only) Resolution or improvement (improvement of = 1 grade in the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scale) of TTP-related signs and symptoms as captured on physical examination and as adverse events, at complete remission and at end of the study drug treatment period (including tapering)(by number of unique subjects and by total number of adverse events (AEs)) Total mortality within the PE treatment period and within the subsequent study drug treatment period (including tapering) • Incidence of PE treatment-related AEs, such as, but not restricted to: haemorrhage from catheter insertion, sepsis, catheter thrombosis, pneumothorax, fluid overload, hypoxia, hypotension, anaphylactoid reactions and transfusion related acute lung injury (TRALI) • Incidence and severity of ALX-0081 treatment-emergent AEs and relationship to study drug • Development of anti-drug antibodies (ADA) = 30 days post-last study drug treatment • PK and PD profile;Timepoint(s) of evaluation of this end point: All secondary endpoints achieved within 30 day period after end of study drug treatment | — |
Countries
Australia, Austria, Belgium, Germany, Israel, Italy, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactDominique Tersago
Ablynx
Outcome results
None listed