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

• ClinicalTrials.gov Identifier: NCT05757570
• Recruitment Status: Recruiting
• First Posted: March 7, 2023
• Last Update Posted: April 29, 2024
• Sponsor: Alpine Immune Sciences, Inc.
• Information provided by (Responsible Party): Alpine Immune Sciences, Inc.

Tracking Information

• First Submitted Date: February 24, 2023
• First Posted Date: March 7, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: July 3, 2023
• Estimated Primary Completion Date: November 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 24, 2023)

Adverse Events [ Time Frame: Study Day 1 through 30 days after last dose of study drug ]

Type, incidence, severity, and seriousness of AEs

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open-label Study of Povetacicept in Subjects With Autoimmune Cytopenias
• Official Title: Open-Label Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Povetacicept in Subjects With Autoimmune Cytopenias (RUBY-4)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

If 2 doses are used in Part 2, it will be randomized, parallel group assignment.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

Drug: povetacicept

Administered by subcutaneous injection every 4 weeks

Other Name: ALPN-303

Study Arms

• Experimental: Part 1: povetacicept 240mg
  Intervention: Drug: povetacicept
• Experimental: Part 2: povetacicept Dose A
  Intervention: Drug: povetacicept
• Experimental: Part 2: povetacicept Dose B
  Intervention: Drug: povetacicept

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 27, 2023): 126
• Original Estimated Enrollment (submitted: February 24, 2023): 42
• Estimated Study Completion Date: November 2027
• Estimated Primary Completion Date: November 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sarah Murphy; 919-786-8898; sarah.murphy@iconplc.com

• Listed Location Countries: Australia, Canada, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05757570
• Other Study ID Numbers: AIS-D04
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alpine Immune Sciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alpine Immune Sciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Allison Naumovski; Alpine Immune Sciences, Inc.

• PRS Account: Alpine Immune Sciences, Inc.
• Verification Date: April 2024