Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ANX005 in Participants With Warm Autoimmune Hemolytic Anemia (wAIHA)

A Phase 2, Open-Label, Repeat Dose Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Intravenous ANX005 in Subjects With Warm Autoimmune Hemolytic Anemia (wAIHA)

This study will evaluate the safety and tolerability of ANX005 in participants with Warm Autoimmune Hemolytic Anemia (wAIHA).

Study Overview

• Status: Completed
• Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
• Intervention / Treatment: Drug: ANX005

Detailed Description

After being informed of study details and potential risks, all participants who provide written informed consent will undergo an up to 6-week screening period to determine eligibility. Participants who meet the eligibility criteria will receive two once-weekly intravenous (IV) infusions of ANX005. Participants will return to the clinic weekly through Week 10 for study assessments. The total duration of individual participation in this study will be up to 16 weeks.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Investigational Site 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or non-pregnant, non-lactating female ≥18 years of age (no maximum age).
• Diagnosis of wAIHA at least 3 months prior to screening with a direct antiglobulin test (DAT) ≥1 positive for immunoglobulin G (IgG)±C3, or a diagnosis of mixed autoimmune hemolytic anemia (AIHA) that is DAT positive for both IgG and C3, with a presence of a cold antibody with a thermal amplitude ≥30ºCelcius.
• Hemoglobin (Hgb) level ≤10.0 grams/deciliter (pre-transfusion).
• Evidence of classical complement pathway activation.
• Evidence of active hemolysis.
• Stable use of glucocorticoids and immunosuppressants are permitted.
• Vaccinations against encapsulated bacterial organisms within 5 years prior to screening or participant must be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination and/or the use of prophylactic antibiotics in accordance with local standards of practice and/or guidelines.

Exclusion Criteria:

• Elevated aspartate aminotransferase or alanine aminotransferase levels >2.5 times the upper limit of normal.
• Platelet count <30 X 10^9/liter.
• History of cold agglutinin disease.
• History of solid organ, bone marrow, or stem cell transplantation.
• History of splenectomy within the 3 months prior to screening.
• Received rituximab or other anti-CD20 monoclonal antibody <3 months prior to screening.
• Intravenous immunoglobulin (IVIg) treatment within 3 months prior to screening or plasmapheresis or immunoadsorption treatment within 60 days prior to screening.
• Clinically significant, recent, or ongoing illness or medical condition, including coexistent autoimmune disorder, malignancy, HIV, hepatitis B virus, and hepatitis C virus.
• History of meningitis or septicemia within the past 2 years.
• Treatment with an investigational therapeutic agent within 30 days prior to screening.
• Hypersensitivity to any drug product or excipients used in this study or to previous IV medication administration.
• Body weight less than 50 kilograms (kg) or greater than 100 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANX005; Participants will receive two once-weekly doses of ANX005 at specific time points	Drug: ANX005; ANX005 is provided as a solution for IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Treatment-emergent adverse events (TEAEs)	Number of participants with TEAEs, defined as any adverse event with an onset on or after the day of infusion through 16 weeks after the infusion	Up to Week 16
Change in disease activity biomarkers	Change in hemoglobin, lactate dehydrogenase, bilirubin, reticulocyte count and haptoglobin from baseline	Baseline to Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations	Plasma concentrations of ANX005 over time	Up to Day 71
Change in complement system biomarkers	Change in CH50 and C1q from baseline	Baseline to Day 71

Collaborators and Investigators

• Sponsor: Annexon, Inc.
• Investigators: Study Director: Study Director, Annexon, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: December 28, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: complement; AIHA; C1q; RBC lysis
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: ANX005-wAIHA-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No