Immune-mediated Thrombotic thrombocytopenic purpura (iTTP) is a rare, autoimmune disorder characterized by life-threatening episodes of thrombocytopenia, microangiopathic hemolytic anemia and organ damage. Patients have an unpredictable course punctuated by relapses associated with autoantibody-mediated (primarily IgG) depletion of ADAMTS13, a key regulator of coagulation. ADAMTS13 deficiency during remission has been associated with increased risk of relapse, but also, and potentially more devastating, ischemic stroke. Until recently, it was presumed that rituximab (a monoclonal antibody targeting B cells) improved relapse-free survival in most patients, but this was based on findings from very small studies. Given concern about stroke and relapse risk, preventive immunosuppression with rituximab has also recently come into practice for patients with falling ADAMTS13 activity (ADAMTS13-relapse). It is expected that following efgartigimod therapy, there will be a rise in ADAMTS13 activity to the normal range that will be sustained during the treatment period. Following withdrawal of therapy, it is expected that most participants will experience a fall in ADAMTS13 activity, demonstrating the safety and efficacy in efgartigimod to reliably but temporarily reduce pathogenic antibodies. This would demonstrate the potential efficacy for efgartigimod as a maintenance therapy to safely prevent relapse of iTTP to be further explored in a larger efficacy study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
intravenous efgartigimod weekly with monitoring of ADAMTS13 activity for 8 weeks, followed by an observational period of 8 weeks or until treatment failure.
University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGsafety of efgartigimod by the incidence of relapse
Relapse rate in the experimental arm compared with the historical rituximab arm
Time frame: 8 weeks post-intervention
safety and tolerability of efgartigimodhistorical rituximab arm
Incidence and severity of adverse events (AEs), AEs of special interest (AESIs) and serious AEs (SEAs)
Time frame: 8 weeks post-intervention
efficacy of efgartigimod to achieve a normal ADAMTS13 activity by Day 60 of the study
Compare the mean ADAMTS13 activity and proportion with normal ADAMTS13 activity at Day 60 and 90 between the experimental and historical cohorts
Time frame: 60 days
efficacy of efgartigimod to prevent the need for other preemptive therapy to rescue severe ADAMTS13 deficiency
Compare the rate use of rescue therapy between the experimental and historical cohort treated with preemptive rituximab, as required by the lack of ADAMTS13 activity increase by 20%
Time frame: 8 weeks post-intervention
the efficacy of efgartigimod to raise ADAMTS13 activity more rapidly than historically treated patients with rituximab
Compare the mean slope of ADAMTS13 rise at the end of treatment (Day 60) and at 90 days between cohorts
Time frame: Day 60 and day 90
the efficacy of efgartigimod to deplete pathogenic ADAMTS13 antibodies
Compare the mean ADAMTS13 antibody titers and proportion with \>50% reduction in antibody titer between cohorts
Time frame: 8 weeks post-intervention
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