An Open-label Study of Povetacicept in Subjects With Autoimmune Cytopenias

Overview

The goal of this clinical study is to evaluate povetacicept in adults with autoimmune cytopenias of immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease to determine if povetacicept is safe and potentially beneficial in treating these diseases. During the study treatment period participants will receive povetacicept approximately every 4 weeks for 6 months, with the possibility of participating in a 6-month study treatment extension period.

Eligibility

Summary of Key Inclusion Criteria:

1. Indication-specific Criteria
   1. Immune Thrombocytopenia (ITP)
      • Documented primary ITP of at least 12 weeks duration
      • History of failure or relapse to at least 2 treatment regimens for ITP
      • History of exposure to a TPO-RA unless otherwise contraindicated or unavailable
      • Documented history of platelets <30 × 10^9/L
   2. Warm Autoimmune Hemolytic Anemia (wAIHA)
      • Diagnosis of primary wAIHA of at least 12 weeks duration documented with a current or prior positive direct antiglobulin test (DAT) for anti-IgG (±C3d)
      • Documented history of anemia with hemoglobin ≤9 g/dL
      • At least one of the following: (i) haptoglobin <LLN (ii) indirect bilirubin >ULN (iii) lactate dehydrogenase>ULN
      • History of failure or relapse to at least 2 treatment regimens for wAIHA
   3. Cold Agglutinin Disease (CAD)
      • Diagnosis of primary CAD of at least 12 weeks duration with all of the following: (i) chronic hemolysis (ii) polyspecific DAT positive (iii) monospecific DAT strongly positive for C3d (iv) cold agglutinin titer ≥64 at 4°C (v) IgG DAT ≤1+ (vi) no overt malignant disease
      • Documented history of anemia with hemoglobin ≤9 g/dL
      • At least one of the following: (i) haptoglobin <LLN (ii) indirect bilirubin >ULN (iii) lactate dehydrogenase>ULN
      • History of failure or relapse to at least 1 treatment regimen for CAD
2. (All indications) If receiving protocol-specified standard-of-care medications, doses

   must be stable for protocol-specified durations

Summary of Key Exclusion Criteria:

1. Secondary AIHA, CAD, or ITP
2. Treatment with any of the following within the noted period prior to study entry
   1. rituximab: <12 weeks
   2. IVIg: <4 weeks
   3. sutimlimab, other marketed biologic therapeutics: <8 weeks
   4. plasmapheresis, plasma exchange, or double-filtration plasmapheresis: <8 weeks
   5. transfusions with blood, blood products or other rescue medications: <2 weeks
   6. splenectomy: <12 weeks
   7. other immunomodulatory or investigational agents, except for investigational agents for COVID-19 that have been granted emergency use authorization or approved by the applicable national health authority: <5 half-lives and requires agreement of the Medical Monitor
3. Recent serious or ongoing infection; risk or history of serious infection