Obexelimab for Autoimmune Hemolytic Anemia

Not currently recruiting at 51 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests obexelimab to evaluate its effectiveness and safety for individuals with Warm Autoimmune Hemolytic Anemia (wAIHA), a condition where the immune system mistakenly destroys red blood cells, leading to anemia. Participants will receive either obexelimab (a humanized Fc-engineered monoclonal antibody against CD19) or a placebo, administered as injections over 24 weeks. The trial seeks individuals diagnosed with wAIHA for at least three months who have tried at least one other treatment without success. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

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.

Is there any evidence suggesting that obexelimab is likely to be safe for humans?

Research has shown that obexelimab has been tested for safety in people with conditions like autoimmune hemolytic anemia. In one study involving individuals with systemic lupus erythematosus, obexelimab was generally well-tolerated. Most side effects were mild to moderate, such as headaches and injection site reactions, and were not severe.

Obexelimab is not yet approved for any condition, but studies have assessed its safety. The current phase of testing suggests that researchers find it safe enough for broader trials. However, like all treatments, some risks or side effects may still occur.

Overall, the safety results are promising, but participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for autoimmune hemolytic anemia, which typically involve steroids or immunosuppressants like rituximab, obexelimab offers a novel approach. Obexelimab is unique because it targets CD19, a protein on the surface of B-cells, interrupting the process that leads to the destruction of red blood cells. This targeted mechanism potentially reduces the side effects often associated with broader immune suppressants. Additionally, obexelimab is administered as a subcutaneous injection, which can be more convenient and less invasive than intravenous treatments. Researchers are excited about obexelimab because it promises a more precise and potentially safer treatment option for patients.

What evidence suggests that obexelimab might be an effective treatment for autoimmune hemolytic anemia?

Research shows that obexelimab, which participants in this trial may receive, could be a promising treatment for Warm Autoimmune Hemolytic Anemia (wAIHA). Obexelimab targets specific proteins on B cells, a type of immune cell involved in the disease. In earlier studies, obexelimab attached to these proteins and might help reduce harmful immune responses. Most patients tolerated it well, experiencing no serious side effects. Although research continues, these findings suggest that obexelimab could help manage wAIHA by controlling the immune system's attack on red blood cells. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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 have been treated for warm autoimmune hemolytic anemia for over 3 months.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39636565/

Pharmacokinetics, Pharmacodynamics, Bioavailability, and ... Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD.

2. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/obexelimab-zenas-biopharma-usa-acquired-autoimmune-hemolytic-anemia-likelihood-of-approval/

Obexelimab by Zenas BioPharma (USA) for Acquired ... According to GlobalData, Phase III drugs for Acquired (Autoimmune) Hemolytic Anemia have a 25% phase transition success rate (PTSR) indication ...

3. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper199848.html

3834 Effect of Obexelimab Surrogate Monoclonal Antibody ... Obexelimab is a bifunctional, non-depleting humanized monoclonal antibody that mimics the action of antigen-antibody complexes by binding CD19 and FcγRIIb to ...

4. go.drugbank.com go.drugbank.com/drugs/DB15032

Obexelimab: Uses, Interactions, Mechanism of Action Obexelimab is under investigation in clinical trial NCT02725515 (A Study of the Effect of XmAb®5871 in Patients With Systemic Lupus ...

5. researchgate.net researchgate.net/publication/332392942_98_Results_of_a_phase_2_double-blind_randomized_placebo-controlled_study_of_a_reversible_B_cell_inhibitor_XmAbR5871_in_systemic_lupus_erythematosus_SLE

98 Results of a phase 2, double-blind, randomized ... Co-ligation of CD19 and FcgammaRIIb inhibits B lineage cells key to lupus pathogenesis. This Phase 2 study in SLE was designed to minimize ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37459248/

Obexelimab in Systemic Lupus Erythematosus With ... This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).

7. zenasbio.com zenasbio.com/our-science/obexelimab/

Our Science Obexelimab Obexelimab, an investigational drug, is a bifunctional monoclonal antibody engineered to mimic the natural antigen-antibody complex for inhibiting B cells.