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

NCT06831058 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HOT-2024-32825
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune-mediated Thrombotic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (4)

• safety of efgartigimod by the incidence of relapse

  Relapse rate in the experimental arm compared with the historical rituximab arm

  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)

  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

  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%

  8 weeks post-intervention

Secondary Outcomes (2)

• the efficacy of efgartigimod to raise ADAMTS13 activity more rapidly than historically treated patients with rituximab

  Day 60 and day 90

• the efficacy of efgartigimod to deplete pathogenic ADAMTS13 antibodies

  8 weeks post-intervention

Study Arms (1)

iTTP patients

EXPERIMENTAL

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

Drug: efgartigimod

Interventions

efgartigimod DRUG

intravenous efgartigimod weekly with monitoring of ADAMTS13 activity for 8 weeks, followed by an observational period of 8 weeks or until treatment failure.

iTTP patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must provide a signed informed consent form
• Subject is 18 years or older at the time of screening
• 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)
• Subject is in clinical remission from iTTP (normal platelet count) for at least 90 days
• Subject has ADAMTS13 activity \< 70% and \> 30% on 2 separate occasions separate by at least 7 days
• Subject is at least 6 months from last dose of rituximab or other intravenous immunosuppression
• If taking other oral immunosuppressants, no change in dose for at least 60 days
• 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

You may not qualify if:

• Subject has been diagnosed with cTTP
• 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
• Subject is unable to understand the nature, scope, and possible consequences of the study.
• Subject is pregnant or lactating
• Subject has a known life-threatening hypersensitivity reaction to efgartigimod

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Interventions

efgartigimod alfa

Study Officials

• Marshall Mazepa, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diondra Howard

CONTACT

651-208-7476; howar709@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 17, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)