Currently, caplacizumab is being developed for treatment of acquired thrombotic thrombocytopenic purpura (TTP). TTP is a rare and potentially life-threatening thrombotic microangiopathy, in which accumulation of ULvWF multimers leads to an increased…
ID
Source
Brief title
Condition
- Red blood cell disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate efficacy of caplacizumab in more rapidly restoring normal platelet
counts as measure of prevention of further microvascular thrombosis
Secondary outcome
- to evaluate the effect of study drug on a composite endpoint consisting of
TTP-related mortality, recurrence of TTP and major thromboembolic events during
study drug treatment
- to evaluate the effect of study drug on prevention of recurrence of TTP over
the entire study period
- to evaluate the effect of study drug on refractoriness to treatment
- to evaluate the effect of study drug on biomarkers of organ damage: lactate
dehydrogenase (LDH), cardiac troponin I (cTnI), and serum creatinine
- to evaluate the effect of study drug on PE parameters (days of PE and
volume), days in intensive care unit (ICU), days in hospital
- adverse events (AEs)
- pharmacodynamic (PD) markers: von Willebrand factor (vWF), coagulation factor
VIII (FVIII), ristocetin cofactor activity (RICO)
- pharmacokinetic (PK) parameters
- immunogenicity (anti-drug antibodies [ADA])
Background summary
Caplacizumab (Sponsor code: ALX-0081) is intended to inhibit the interaction
between von Willebrand factor (vWF) and platelets, by targeting the A1 domain
of vWF. Caplacizumab selectively prevents thrombus formation in high-shear
blood vessels, blocks ultra-large (UL) vWF mediated platelet interactions, and
is expected not to interact with hemostasis in normal, healthy blood vessels.
Study objective
Currently, caplacizumab is being developed for treatment of acquired thrombotic
thrombocytopenic purpura (TTP). TTP is a rare and potentially life-threatening
thrombotic microangiopathy, in which accumulation of ULvWF multimers leads to
an increased risk of thrombus formation in small blood vessels due to excessive
platelet aggregation.
Study design
This is a phase III, double blind, placebo-controlled, randomized study to
evaluate the efficacy and safety of caplacizumab treatment when administered in
addition to standard of care treatment in subjects with an acute episode of
acquired TTP. The study will evaluate the efficacy of caplacizumab in more
rapidly restoring normal platelet counts and the effect of treatment with
caplacizumab on a composite endpoint of TTP-related mortality, prevention of
recurrence of the presenting TTP episode and prevention of major thromboembolic
events during study drug treatment.
After confirmation of eligibility to study participation and after the start of
PE treatment*, subjects will be randomized in a ratio of 1:1 to either receive
caplacizumab or placebo in addition to standard of care therapy. Randomization
will be stratified by severity of neurological symptoms (Glasgow coma scale
[GCS]).
Intervention
Screening
- Obtain informed consent
- Review of eligibility criteria
- Medical history, including TTP history (and ADAMTS-13 activity levels at
admission, if available)
- GCS
- Bleeding assessment
- Platelet count, blood smear, serum creatinine (local lab)
- Pregnancy test (urine or blood)
- Demographics
- Concomitant medication
- AEs
Day 1
- Randomization
- Study drug administration and PE + corticosteroids
- Platelet count, blood smear
- LDH, serum creatinine, cTnI, ADAMTS13 activity
- Complement factors C5a and C5b-9
- Assessment of the neurological system (including coma, stupor, seizures,
disorientation/confusion, hemiparesis/-plegia, focal deficit, agitation,
dysarthria)
- Cognitive assessment (standardized mini mental state examination [SMMSE])
- Clinically significant TTP event
- AEs, safety laboratory parameters, physical examination, electrocardiogram
(ECG), vital signs
- Concomitant medication
- Bleeding assessment
- PK, PD parameters (vWF, FVIII and RICO)
- Immunogenicity (ADA)
Study drug treatment period (including exacerbation during 30-day post daily PE
period and relapse during treatment extension period), the possible treatment
extension period and FU period - see Schedules of Assessments.
Study burden and risks
The following items are not part of the standard of care for this condition and
are an additional burden for the study subjects associated with participation
in the study: urine pregnancy test, 30 days follow up after the end of the
plasma exchange with daily subcutaneous injections and weekly visits to the
hospital & 2 follow-up visits after last dosing.
Technologiepark 21
Zwijnaarde 9052
BE
Technologiepark 21
Zwijnaarde 9052
BE
Listed location countries
Age
Inclusion criteria
1.Adult male or female * 18 years of age at the time of signing the informed consent form (ICF)
2.Clinical diagnosis of acquired TTP (initial or recurrent), which includes thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g. schistocytes)
3.Requires initiation of daily PE treatment and has received 1 PE treatment prior to randomization .
Exclusion criteria
* Platelet count *100×109/L
* Serum creatinine level >200 *mol/L in case platelet count is > 30×109/L (to exclude possible cases of atypical Hemolytic Uremic Syndrome [aHUS])
* Known other causes of thrombocytopenia including but not limited to:
- Clinical evidence of enteric infection with E. coli 0157 or related organism
- Atypical HUS
- Hematopoietic stem cell, bone marrow or organ transplantation-associated thrombotic microangiopathy
- Known or suspected sepsis
- Diagnosis of disseminated intravascular coagulation
* Congenital TTP (known at the time of study entry)
* Pregnancy or breast-feeding
* Clinically significant active bleeding or high risk of bleeding (excluding thrombocytopenia)
* Known chronic treatment with anticoagulant treatment that cannot be stopped (interrupted) 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
* Malignant arterial hypertension
* Clinical condition other than that associated with TTP, with life expectancy < 6 months, such as end-stage malignancy
* Subjects who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001098-42-NL |
| ClinicalTrials.gov | NCT02553317 |
| CCMO | NL54235.058.15 |