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

• ClinicalTrials.gov Identifier: NCT04691570
• Recruitment Status: Not yet recruiting
• First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Sponsor: Annexon, Inc.
• Information provided by (Responsible Party): Annexon, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Warm Autoimmune Hemolytic Anemia (wAIHA)	Drug: ANX005	Phase 2

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Estimated Study Start Date: January 2021
• Estimated Primary Completion Date: November 15, 2021
• Estimated Study Completion Date: February 15, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety: Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to Week 16 ]
   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

Secondary Outcome Measures :

1. Plasma concentrations [ Time Frame: Up to Day 71 ]
   Plasma concentrations of ANX005 over time
2. Change in complement system biomarkers [ Time Frame: Baseline to Day 71 ]
   Change in CH50 and C1q from baseline
3. Change in disease activity biomarkers [ Time Frame: Baseline to Day 71 ]
   Change in hemoglobin, lactate dehydrogenase, bilirubin, and haptoglobin from baseline

Eligibility Criteria

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

Criteria

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.
• Hemoglobin (Hgb) level <10.0 g /dL (pre-transfusion).
• Positive direct antiglobulin test (DAT) ≥ 1+ for C3d and immunoglobulin G (IgG).
• Evidence of classical complement pathway activation.
• CH50 below the lower limit of normal.
• 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 complete vaccinations at least 2 weeks prior to dosing with ANX005.

Exclusion Criteria:

• Elevated aspartate aminotransferase or alanine aminotransferase levels >2.5 times the upper limit of normal.
• Platelet count < 30 X 10^9/L.
• 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 kg or greater than 100 kg.

Contacts and Locations

Contacts

Contact: Study Coordinator; 650-822-5500; clinicaltrials@annexonbio.com

Sponsors and Collaborators

Annexon, Inc.

Investigators

• Principal Investigator: Morie Gertz, MD; Mayo Clinic, Rochester, MN

More Information

• Responsible Party: Annexon, Inc.
• ClinicalTrials.gov Identifier: NCT04691570
• Other Study ID Numbers: ANX005-wAIHA-02
• First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Annexon, Inc.:

AIHA; C1q; complement; RBC lysis

Additional relevant MeSH terms:

Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Hemolysis; Hematologic Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases