Obexelimab for Autoimmune Hemolytic Anemia

Recruiting at 49 trial locations

Overseen By Zenas Patient Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Zenas BioPharma (USA), LLC

Must not be taking: B cell-depleting, Biologic immunomodulators

Disqualifiers: Cold AIHA, Transfusion, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

134 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests obexelimab, an injectable medication, in patients with Warm Autoimmune Hemolytic Anemia who haven't responded to other treatments. It aims to manage the immune system's attack on red blood cells.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot be on more than 2 medications for wAIHA treatment. Also, certain treatments like B cell-targeted agents or IV Ig should not have been used recently.

What evidence supports the effectiveness of the drug Obexelimab for treating autoimmune hemolytic anemia?

Obexelimab has shown promise in treating systemic lupus erythematosus (SLE), another autoimmune condition, by inhibiting B cells, which are part of the immune system. This suggests it might also help in autoimmune hemolytic anemia, as both conditions involve the immune system attacking the body's own cells. ^{1 2 3 4 5}

What safety data exists for Obexelimab in humans?

There is no specific safety data available for Obexelimab in the provided research articles. ^{1 2 6 7 8}

How is the drug Obexelimab unique in treating autoimmune hemolytic anemia?

Obexelimab is unique because it is a bifunctional monoclonal antibody that targets CD19 and FcyRIIb to inhibit B cells, which are involved in the immune response causing the anemia. This mechanism is different from other treatments like rituximab, which targets CD20, making Obexelimab a novel approach for autoimmune hemolytic anemia. ^{1 2 3 5 9}

Eligibility Criteria

Adults diagnosed with Warm Autoimmune Hemolytic Anemia (wAIHA) who have tried at least one treatment without success can join. They must show symptoms of anemia and have had wAIHA for over three months. People can't join if they've had recent blood transfusions, used certain immune therapies in the past six months, or are on more than two wAIHA medications.

Inclusion Criteria

I have tried at least one treatment for wAIHA that didn't work.

Other inclusion criteria apply

I am 18 years old or older.

Exclusion Criteria

I am taking more than 2 medications for warm autoimmune hemolytic anemia.

I haven't used any B cell-targeting treatments in the last 6 months.

I have not received IV Ig or epoetin alfa in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Safety and Dose Confirmation Run-in Period (SRP)

Participants receive obexelimab administered as subcutaneous injections for 24 weeks

24 weeks

5 visits (in-person) in the first 5 weeks, then every 2 weeks

Randomized Control Period (RCP)

Participants are randomized to receive either obexelimab or placebo administered as subcutaneous injections for 24 weeks

24 weeks

5 visits (in-person) in the first 5 weeks, then every 2 weeks

Open Label Extension (OLE)

Participants have the opportunity to receive obexelimab for up to 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Obexelimab
• Placebo

Trial Overview The trial is testing Obexelimab's effectiveness and safety against a placebo in treating wAIHA. Participants will be randomly assigned to receive either Obexelimab or a placebo to compare outcomes between the two groups.

Participant Groups

Group I: Safety and Dose Confirmation Run-in Period (SRP): Obexelimab Experimental Treatment 1 Intervention

Obexelimab will be administered as an SC injection for 24 weeks.

Group II: Randomized Control Period (RCP): Obexelimab Experimental Treatment 1 Intervention

Obexelimab will be administered as an SC injection for 24 weeks.

Group III: Randomized Control Period (RCP): Placebo Placebo Group 1 Intervention

Placebo will be administered as an SC injection for 24 weeks

Who Is Running the Clinical Trial?

Zenas BioPharma (USA), LLC

Lead Sponsor

Trials

8

Recruited

760+

Findings from Research

In a study of 7 patients with refractory and recurrent autoimmune hemolytic anemia, the combination of rituximab and cyclophosphamide resulted in a complete response in 6 out of 7 patients, demonstrating high efficacy.

The treatment was well-tolerated with only mild side effects, and all patients remained in remission during a 12-month follow-up, indicating both safety and long-term effectiveness of the regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The long-term efficacy and safety of rituximab combined with cyclophosphamide in treatment of seven patients with refractory and recurrent autoimmune hemolytic anemia]. Liu, H., Xing, LM., Wang, HQ., et al.[2015]

In a trial involving 104 patients with systemic lupus erythematosus (SLE), obexelimab treatment did not meet the primary endpoint of significantly reducing the proportion of patients experiencing loss of improvement (LOI) compared to placebo, but it did show a significant increase in time to LOI for those treated with obexelimab.

Obexelimab was generally safe and well-tolerated, although it caused infusion reactions; it effectively reduced B cell levels by about 50%, suggesting a potential mechanism for its action in treating SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial. Merrill, JT., Guthridge, J., Smith, M., et al.[2023]

Obexelimab, an engineered anti-CD19 antibody, effectively suppresses B cell activation by co-engaging the B cell receptor (BCR) and Fcγ receptor IIb (FcγRIIb), demonstrating its potential as a therapeutic target in autoimmune diseases like systemic lupus erythematosus (SLE).

In studies with genetically modified mice, the treatment maintained B cell numbers while rendering them less responsive to activation signals for at least 14 days, indicating a promising safety profile and efficacy for future clinical trials in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of B cell activation following in vivo co-engagement of B cell antigen receptor and Fcγ receptor IIb in non-autoimmune-prone and SLE-prone mice. Chu, SY., Pong, E., Bonzon, C., et al.[2021]

Monoclonal antibodies (mAbs) and IgG Fc fusion proteins are promising treatments for chronic inflammatory conditions and autoimmune diseases due to their high specificity, potency, and long half-life, allowing for effective and prolonged therapy.

However, their use carries risks of significant immunosuppression and adverse immune reactions, necessitating thorough nonclinical safety assessments and risk mitigation strategies to ensure patient safety during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized nonclinical safety assessment strategies supporting clinical development of therapeutic monoclonal antibodies targeting inflammatory diseases. Brennan, FR., Cauvin, A., Tibbitts, J., et al.[2014]

Therapeutic antibodies are highly effective due to their specific binding capabilities and the long half-life provided by the Fc portion interacting with the FcRn receptor, which enhances their therapeutic potential.

Engineering the Fc portion of antibodies can improve their efficacy by increasing their binding to FcRn or enhancing their ability to trigger immune responses, potentially leading to better patient outcomes and more convenient dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methods to engineer and identify IgG1 variants with improved FcRn binding or effector function. Kelley, RF., Meng, YG.[2012]

References

1. China pubmed.ncbi.nlm.nih.gov

[The long-term efficacy and safety of rituximab combined with cyclophosphamide in treatment of seven patients with refractory and recurrent autoimmune hemolytic anemia]. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic anemia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of B cell activation following in vivo co-engagement of B cell antigen receptor and Fcγ receptor IIb in non-autoimmune-prone and SLE-prone mice. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Optimized nonclinical safety assessment strategies supporting clinical development of therapeutic monoclonal antibodies targeting inflammatory diseases. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Methods to engineer and identify IgG1 variants with improved FcRn binding or effector function. [2012]

9. England pubmed.ncbi.nlm.nih.gov

Antibody based therapeutics for autoimmune hemolytic anemia. [2023]