An Open-label Study of Povetacicept in Participants With Autoimmune Cytopenias (RUBY-4)

Alpine Immune Sciences

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: povetacicept

Study type: Interventional

Funder types: Industry

Identifiers

NCT05757570

AIS-D04

2023-507067-19-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Indication-specific Criteria

   1. Immune Thrombocytopenia (ITP)

      • Documented persistent or chronic primary ITP of at least 12 weeks duration from diagnosis to Cycle 1 Day 1
      • 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 ≤10 g/dL
      • At least one of the following: (i) haptoglobin < lower limit of normal (LLN) (ii) indirect bilirubin > upper limit of normal (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 ≤10 g/dL
      • Evidence of hemolysis during screening: (i) indirect bilirubin >ULN and (ii) lactate dehydrogenase>ULN or haptoglobin <LLN
      • 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

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, any use after initiation of screening is exclusionary
   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

Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Part 1: Povetacicept 240mg

Experimental group

Description:

Participants grouped in 3 cohorts by diagnosis will be administered Povetacicept

Treatment:

Drug: povetacicept

Part 2: Povetacicept Dose A

Experimental group

Description:

Based on the findings of Part 1, one or two dose levels may be assessed in Part 2; if two dose levels are assessed participants will be randomized to receive one of the two dose levels of Povetacicept

Treatment:

Drug: povetacicept