Clinical trial NCT06831058: A Pilot Study of Efgartigimod for Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
Official title: A Pilot Study of Efgartigimod for Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Immune-mediated Thrombotic Thrombocytopenic Purpura
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2025-02-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: safety of efgartigimod by the incidence of relapse
timeFrame: 8 weeks post-intervention
measure: safety and tolerability of efgartigimodhistorical rituximab arm
timeFrame: 8 weeks post-intervention
measure: efficacy of efgartigimod to achieve a normal ADAMTS13 activity by Day 60 of the study
timeFrame: 60 days
measure: efficacy of efgartigimod to prevent the need for other preemptive therapy to rescue severe ADAMTS13 deficiency
timeFrame: 8 weeks post-intervention
Secondary outcomes:
measure: the efficacy of efgartigimod to raise ADAMTS13 activity more rapidly than historically treated patients with rituximab
timeFrame: Day 60 and day 90
measure: the efficacy of efgartigimod to deplete pathogenic ADAMTS13 antibodies
timeFrame: 8 weeks post-intervention
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Marshall Mazepa, MD
role: PRINCIPAL_INVESTIGATOR
References: