A Pilot Study of Efgartigimod for Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

Phase 2

Not yet recruiting

• Conditions: Immune-mediated Thrombotic Thrombocytopenic Purpura
• Interventions: Drug: efgartigimod

• Registration Number: NCT06831058
• Lead Sponsor: University of Minnesota

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-13
• Study First Submitted QC: 2025-02-13
• Last Update Submitted: 2025-02-13
• Study First Posted: 2025-02-17
• Last Update Posted: 2025-02-17
• Study Start: 2025-05-01
• Primary Completion: 2028-05-01
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Subject must provide a signed informed consent form
2. Subject is 18 years or older at the time of screening
3. Subject has a prior history of iTTP as defined by the presence of ADAMTS13 activity < 10% with ADAMTS13 antibodies or inhibitor, thrombocytopenia (platelet count < 100) and microangiopathic hemolytic anemia (defined by the presence of schistocytes on blood smear)
4. Subject is in clinical remission from iTTP (normal platelet count) for at least 90 days
5. Subject has ADAMTS13 activity < 70% and > 30% on 2 separate occasions separate by at least 7 days
6. Subject is at least 6 months from last dose of rituximab or other intravenous immunosuppression
7. If taking other oral immunosuppressants, no change in dose for at least 60 days
8. Female subjects of childbearing potential must present with a negative pregnancy test and agree to employ highly effective birth control measures for duration of study.

Sexually active male subjects must agree to use an effective method of contraception for the duration of the study

Exclusion Criteria

1. Subject has been diagnosed with cTTP
2. Subject has been exposed to another investigational product within 30 days prior to enrollment or is scheduled to participate in another clinical study involving investigational product or investigational device during the course of the study
3. Subject is unable to understand the nature, scope, and possible consequences of the study.
4. Subject is pregnant or lactating
5. Subject has a known life-threatening hypersensitivity reaction to efgartigimod

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
iTTP patients	efgartigimod	participants with a history of iTTP in clinical remission but with ADAMTS13 deficiency (\>30% but \< 70% activity)

Primary Outcome Measures

Name	Time	Method
safety of efgartigimod by the incidence of relapse	8 weeks post-intervention	Relapse rate in the experimental arm compared with the historical rituximab arm
safety and tolerability of efgartigimodhistorical rituximab arm	8 weeks post-intervention	Incidence and severity of adverse events (AEs), AEs of special interest (AESIs) and serious AEs (SEAs)
efficacy of efgartigimod to achieve a normal ADAMTS13 activity by Day 60 of the study	60 days	Compare the mean ADAMTS13 activity and proportion with normal ADAMTS13 activity at Day 60 and 90 between the experimental and historical cohorts
efficacy of efgartigimod to prevent the need for other preemptive therapy to rescue severe ADAMTS13 deficiency	8 weeks post-intervention	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%

Secondary Outcome Measures

Name	Time	Method
the efficacy of efgartigimod to raise ADAMTS13 activity more rapidly than historically treated patients with rituximab	Day 60 and day 90	Compare the mean slope of ADAMTS13 rise at the end of treatment (Day 60) and at 90 days between cohorts
the efficacy of efgartigimod to deplete pathogenic ADAMTS13 antibodies	8 weeks post-intervention	Compare the mean ADAMTS13 antibody titers and proportion with \>50% reduction in antibody titer between cohorts