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

Study Overview
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Brief Summary
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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.

Official Title
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Open-Label Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Povetacicept in Subjects With Autoimmune Cytopenias (RUBY-4)

Conditions
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Immune Thrombocytopenia, Idiopathic Thrombocytopenic Purpura, Warm Autoimmune Hemolytic Anemia, Cold Agglutinin Disease

Intervention / Treatment
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* Drug: povetacicept


Participation Criteria
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Eligibility Criteria
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Summary of Key Inclusion Criteria: Indication-specific Criteria 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 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 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 (All indications) If receiving protocol-specified standard-of-care medications, doses must be stable for protocol-specified durations Summary of Key Exclusion Criteria: Secondary AIHA, CAD, or ITP Treatment with any of the following within the noted period prior to study entry rituximab: <12 weeks IVIg: <4 weeks sutimlimab, other marketed biologic therapeutics: <8 weeks plasmapheresis, plasma exchange, or double-filtration plasmapheresis: <8 weeks transfusions with blood, blood products or other rescue medications: <2 weeks splenectomy: <12 weeks 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 Recent serious or ongoing infection; risk or history of serious infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: If 2 doses are used in Part 2, it will be randomized, parallel group assignment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: povetacicept 240mg<br> | Drug: povetacicept<br>* Administered by subcutaneous injection every 4 weeks<br>* Other names: ALPN-303;|
| Experimental: Part 2: povetacicept Dose A<br> | Drug: povetacicept<br>* Administered by subcutaneous injection every 4 weeks<br>* Other names: ALPN-303;|
| Experimental: Part 2: povetacicept Dose B<br> | Drug: povetacicept<br>* Administered by subcutaneous injection every 4 weeks<br>* Other names: ALPN-303;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Type, incidence, severity, and seriousness of AEs | Study Day 1 through 30 days after last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ITP, Immune Thrombocytopenia, Warm Autoimmune Hemolytic Anemia, Cold Agglutinin Disease, Autoimmune Cytopenia, Idiopathic Thrombocytopenic Purpura, Immune Thrombocytopenic Purpura, Hemolytic Anemia, RUBY4, RUBY-4, Povetacicept, ALPN-303, ALPN303, Autoimmune Hemolytic Anemia, wAIHA, AIHA, CAD