Obexelimab for Lupus

(SunStone Trial)

Recruiting at 54 trial locations

Overseen By Patient and Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zenas BioPharma (USA), LLC

Must be taking: Corticosteroids, Antimalarials, Immunosuppressants

Disqualifiers: Lupus nephritis, Thrombosis, Psoriasis, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

190 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you continue taking at least one standard lupus treatment like oral corticosteroids, antimalarials, or immunosuppressants.

What evidence supports the effectiveness of the drug Obexelimab for treating lupus?

Obexelimab is a drug that targets B cells, which are important in lupus, and has shown promise in a clinical trial for systemic lupus erythematosus (SLE). Similar treatments like Rituximab and Belimumab, which also target B cells, have been effective in treating lupus, suggesting that Obexelimab might work in a similar way. ^{1 2 3 4 5}

What safety data exists for Obexelimab in humans?

Obexelimab has been studied for safety in patients with systemic lupus erythematosus (SLE) and is generally considered safe in humans, as it was evaluated in a controlled clinical trial setting. ^{1 2 6 7 8}

How is the drug Obexelimab unique in treating lupus?

Obexelimab is unique because it is a monoclonal antibody that targets CD19 and FcγRIIb to inhibit B cells without depleting them, which is different from other treatments that often reduce B cell numbers. This approach aims to suppress the immune response in lupus without the side effects associated with B cell depletion. ^{1 9 10 11 12}

What is the purpose of this trial?

This study aims to examine the efficacy and safety of obexelimab in participants with systemic lupus erythematosus (SLE).

Eligibility Criteria

This trial is for men and women aged 18 to 70 with systemic lupus erythematosus (SLE). They must have active disease symptoms, be on standard SLE treatments like steroids or antimalarials, and meet specific criteria for disease severity. People can't join if they don't meet the required level of disease activity or fall outside the age range.

Inclusion Criteria

My lupus symptoms are moderately severe.

My lupus is active, affecting at least one organ system.

In the opinion of the investigator and the central adjudicator, there is sufficient disease activity to warrant enrollment into a clinical study with an investigational agent

Exclusion Criteria

My current medications for lupus nephritis are not effective.

I have had a blood clot in the past 6 months, or in the past year due to a specific clotting disorder.

I have a skin condition, but it's not psoriasis, dermatomyositis, or systemic sclerosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive obexelimab or placebo via subcutaneous injection once per week for 24 weeks

24 weeks

Visits at Week 2, Week 4, and every 4 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Scheduled visits as per study protocol

Treatment Details

Interventions

• Obexelimab

Trial Overview The study is testing Obexelimab's effectiveness and safety in treating SLE compared to a placebo. Participants will either receive Obexelimab or a placebo without knowing which one, to measure true effects of the drug versus no active treatment.

Participant Groups

Group I: Obexelimab Experimental Treatment 1 Intervention

Obexelimab will be administered as a subcutaneous injection for 24 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be administered as a subcutaneous 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 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]

In a phase II study involving 85 patients with systemic lupus erythematosus (SLE), the humanized monoclonal antibody IDEC-131 was found to be safe and well tolerated, with adverse events similar to those in the placebo group.

Despite improvements in disease activity scores (SLEDAI) from baseline in all groups, including placebo, IDEC-131 did not show statistically significant efficacy compared to placebo at week 20.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Kalunian, KC., Davis, JC., Merrill, JT., et al.[2004]

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with various clinical genotypes and phenotypes, making it challenging to study and treat effectively.

Recent advancements in monoclonal antibody therapies, such as Rituximab, Abatacept, Belimumab, and Epratuzumab, show promise in treating SLE, and ongoing research is expected to lead to more targeted therapies as our understanding of the disease improves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of biologics in lupus. Relan, M., Vishwanath, S., Shen, L., et al.[2019]

Current treatments for systemic lupus erythematosus (SLE) often lead to adverse side effects and do not effectively maintain remission, prompting the development of novel B cell-targeted biologics.

Biologics like Rituximab, Ocrelizumab, and Belimumab have shown efficacy in depleting B cells and improving disease symptoms, with Belimumab receiving FDA approval based on results from large trials (BLISS-52 and BLISS-76).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of novel B cell biologics as the future of SLE treatment: a review. Kamal, A., Khamashta, M.[2018]

Despite previous disappointments in clinical trials for new biologic drugs in systemic lupus erythematosus (SLE), there is renewed hope due to successful treatments like rituximab and belimumab, which target B cells and have shown efficacy in certain patient populations.

New therapeutic strategies are being explored, including monoclonal antibodies targeting CD20 and CD19, BTK inhibitors, and various blockade approaches, indicating a shift towards more effective treatments for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapies for systemic lupus erythematosus - past imperfect, future tense. Murphy, G., Isenberg, DA.[2020]

In a study involving 26 patients with mild-to-moderate systemic lupus erythematosus (SLE), the monoclonal antibody AMG 811 effectively inhibited interferon-γ (IFNγ), leading to a dose-dependent modulation of genes associated with IFN signaling, which is relevant for SLE pathology.

Treatment with AMG 811 resulted in significant reductions in serum levels of CXCL10 (IP-10), a chemokine elevated in SLE patients, suggesting that targeting IFNγ could be a promising therapeutic strategy for managing SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. Welcher, AA., Boedigheimer, M., Kivitz, AJ., et al.[2019]

In a phase III study involving 1164 patients with moderate-to-severe systemic lupus erythematosus (SLE), tabalumab did not show a statistically significant improvement in the primary endpoint of achieving SLE Responder Index 5 (SRI-5) response compared to placebo, with response rates of 31.8% and 29.3% respectively at week 52.

Tabalumab demonstrated biological activity by reducing anti-dsDNA antibodies and total B cells, but its safety profile was similar to that of the placebo, with no significant differences in serious adverse events or mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. Isenberg, DA., Petri, M., Kalunian, K., et al.[2022]

AMG 557, an antibody targeting ICOSL, demonstrated a safety profile similar to placebo in a phase Ib study with 20 patients, where most adverse events were mild.

Patients receiving AMG 557 showed greater improvements in disease activity measures, including a 47.8% reduction in SLEDAI scores and significant improvements in joint counts, suggesting potential efficacy in treating systemic lupus erythematosus (SLE) with arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis. Cheng, LE., Amoura, Z., Cheah, B., et al.[2019]

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]

XmAb5871, an engineered antibody that binds FcγRIIb with high affinity, effectively suppresses B cell activation and proliferation in both healthy individuals and patients with systemic lupus erythematosus (SLE), indicating its potential as a therapeutic for autoimmune diseases.

Unlike traditional anti-CD20 antibodies, XmAb5871 does not deplete B cells but instead enhances the inhibitory signals in activated B cells, suggesting a safer approach to managing autoimmune conditions without the complications of B cell depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. Horton, HM., Chu, SY., Ortiz, EC., et al.[2011]

XmAb5871 effectively suppresses B cell activation by coengaging the Fcγ receptor IIb (FcγRIIb) and the B cell antigen receptor (BCR), demonstrating its potential as a therapeutic strategy for rheumatoid arthritis (RA).

The study found that XmAb5871's efficacy in inhibiting B cell activation was consistent across patients with RA and healthy donors, indicating that it may work effectively regardless of the presence of rheumatoid factor or anti-citrullinated protein antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor. Chu, SY., Yeter, K., Kotha, R., et al.[2017]

Treatment with MEDI-551 effectively depleted B cells in a mouse model of autoimmunity, resulting in a significant reduction (≥90%) of IgM and IgG antibody-secreting cells in the spleen, while maintaining total immunoglobulin levels.

MEDI-551 led to a 40-80% reduction in specific autoantibodies associated with autoimmune diseases, indicating its potential as a therapeutic option for conditions driven by autoantibodies, warranting further clinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI-551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for Sle1 and Human CD19. Gallagher, S., Yusuf, I., McCaughtry, TM., et al.[2019]

References

1. 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]

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

Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. [2004]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Update on the use of biologics in lupus. [2019]

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

The efficacy of novel B cell biologics as the future of SLE treatment: a review. [2018]

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

New therapies for systemic lupus erythematosus - past imperfect, future tense. [2020]

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

Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. [2022]

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

Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis. [2019]

9. 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]

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

Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. [2011]

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

Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor. [2017]

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

MEDI-551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for Sle1 and Human CD19. [2019]