Clinical trial NCT05757570: An Open-label Study of Povetacicept in Participants 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Immune Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Warm Autoimmune Hemolytic Anemia
Cold Agglutinin Disease
Keywords: 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
ITP
wAIHA
AIHA
CAD
Lead sponsor: Alpine Immune Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-07
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability as Assessed by Adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: Study Day 1 through 30 days after last dose of study drug
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Investigational Site (230)
state: California
city: Washington
country: United States
facility: Investigational Site (401)
state: District of Columbia
city: Cooper City
country: United States
facility: Investigational Site (419)
state: Florida
city: Miami
country: United States
facility: Investigational Site (425)
state: Florida
city: Iowa City
country: United States
facility: Investigational Site (219)
state: Iowa
city: Columbia
country: United States
facility: Investigational Site (435)
state: Maryland
city: Bronx
country: United States
facility: Investigational Site (422)
state: New York
city: Lake Success
country: United States
facility: Investigational site (405)
state: New York
city: New Hyde Park
country: United States
facility: Investigational Site (423)
state: New York
city: New York
country: United States
facility: Investigational Site (421)
state: New York
city: New York
country: United States
facility: Investigational Site (404)
state: New York
city: Shirley
country: United States
facility: Investigational Site (420)
state: New York
city: Charlotte
country: United States
facility: Investigational Site (414)
state: North Carolina
city: Greenville
country: United States
facility: Investigational Site (402)
state: North Carolina
city: Seattle
country: United States
facility: Investigational Site (411)
state: Washington
city: Box Hill
country: Australia
facility: Investigational Site (410)
city: Concord
country: Australia
facility: Investigational Site (519)
city: Douglas
country: Australia
facility: Investigational Site (517)
city: Liverpool
country: Australia
facility: Investigational Site (413)
city: West Perth
country: Australia
facility: Investigational Site (407)
city: Westmead
country: Australia
facility: Investigational Site (409)
city: Vienna
country: Austria
facility: Investigational Site (434)
city: Greenfield Park
country: Canada
facility: Investigational Site (406)
city: Hamilton
country: Canada
facility: Investigational Site (403)
city: Toronto
country: Canada
facility: Investigational Site (444)
city: Essen
country: Germany
facility: Investigational Site (438)
city: Meldola
country: Italy
facility: Investigational Site (432)
city: Milan
country: Italy
facility: Investigational Site (428)
city: Novara
country: Italy
facility: Investigational Site (431)
city: Trieste
country: Italy
facility: Investigational Site (443)
city: Grålum
country: Norway
facility: Investigational Site (433)
city: Trondheim
country: Norway
facility: Investigational Site (437)
city: Barcelona
country: Spain
facility: Investigational Site (436)
city: Burgos
country: Spain
facility: Investigational Site (429)
city: Madrid
country: Spain
facility: Investigational Site (430)
city: Murcia
country: Spain
facility: Investigational Site (426)
city: Seville
country: Spain
facility: Investigational Site (427)
city: Ankara
country: Turkey
facility: Investigational Site (415)
city: Ankara
country: Turkey
facility: Investigational Site (416)
city: Istanbul
country: Turkey
facility: Investigational Site (418)
city: Leeds
country: United Kingdom
facility: Investigational Site (442)
city: London
country: United Kingdom
facility: Investigational Site (439)
city: London
country: United Kingdom
facility: Investigational Site (441)
city: London
country: United Kingdom
facility: Investigational Site (440)
Study officials:
affiliation: Alpine Immune Sciences, Inc.
name: Allison Naumovski
role: STUDY_DIRECTOR
References: