Obexelimab for Lupus
(SunStone Trial)
Recruiting in Palo Alto (17 mi)
+35 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Zenas BioPharma (USA), LLC
Must be taking: Corticosteroids, Antimalarials, Immunosuppressants
Disqualifiers: Lupus nephritis, Thrombosis, Psoriasis, others
Prior Safety Data
Trial Summary
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).
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.
12345What 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.
12678How 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.
19101112Eligibility 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.
I am between 18 and 70 years old.
+3 more
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.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ObexelimabExperimental Treatment1 Intervention
Obexelimab will be administered as a subcutaneous injection for 24 weeks.
Group II: PlaceboPlacebo Group1 Intervention
Placebo will be administered as a subcutaneous injection for 24 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sierra Pacific Arthritis and Rheumatology CentersFresno, CA
Clinical Research of West Florida, IncClearwater, FL
Clinical Research of West Florida, Inc.Tampa, FL
Accurate Clinical ResearchLake Charles, LA
More Trial Locations
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Who Is Running the Clinical Trial?
Zenas BioPharma (USA), LLCLead Sponsor
References
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]Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).
Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. [2004]To evaluate the safety and efficacy of a humanized monoclonal antibody against CD154 (IDEC-131) in patients with active systemic lupus erythematosus (SLE).
Update on the use of biologics in lupus. [2019]Systemic lupus erythematosus is more than a heterogeneous autoimmune disease. It is in fact a syndrome of many different clinical genotypes and phenotypes. This review covers the most recently studied monoclonal antibodies and those currently being investigated. The key trials are summarized, including those for biologics on the market for two decades and those just approved for lupus less than two years ago. The focus will be on the following four: Rituximab, Abatacept, Belimumab, and Epratuzumab. It is a challenge to design the perfect trial and study patients with this disease as each has his or her own unique manifestations, biological markers, and underlying genetic background. However, as our understanding of the immune mechanisms involved in lupus increases; novel therapies will emerge that can be utilized for appropriately selected patients.
The efficacy of novel B cell biologics as the future of SLE treatment: a review. [2018]Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with wide ranging multi-systemic effects. Current understanding centralises B cells in SLE pathogenesis with clinical features resulting from autoantibody formation, immune complex deposition, antigen presentation and cytokine activation. Existing standard of care therapies generates adverse side effects; secondary to corticosteroid use and untargeted immunosuppression. The inability to uphold remission and abolish the disease process, in addition to the increasing numbers of patients seen with refractory disease with these therapies, has provoked the development of novel B cell biologics targeting specific pathogenic pathways fundamental to the SLE disease process. Current evidence highlighting the efficacy of Rituximab, Ocrelizumab and Epratuzumab in inducing B cell depletion and achieving disease amelioration through specific B cell surface receptor antagonism is discussed. We review the efficacy of Atacicept, Briobacept and Belimumab in antagonising B lymphocyte stimulator (BLyS) and A proliferation inducing ligand (APRIL), two stimulatory cytokines crucial to B cell survival, growth and function. Two large multicentre randomised controlled trials, BLISS-52 and BLISS-76, have led to FDA approval of Belimumab. Following this breakthrough, other anti-BLyS therapies, Blisibimod and Tabalumab, are currently under Phase III evaluation. Similarly, murine models and Phase I/II trials have demonstrated significant efficacy of Rituximab, Epratuzumab, Briobacept and Atacicept as potential future therapies and we now eagerly await results from Phase III trials. Future research must compare the efficacy of different biologics amongst different patient subpopulations and SLE manifestations, in order to develop clinically and cost effective therapies.
New therapies for systemic lupus erythematosus - past imperfect, future tense. [2020]The failure of many new, mostly biologic, drugs to meet their primary end points in double-blind clinical trials in patients with systemic lupus erythematosus (SLE) has caused a profound sense of disappointment among both physicians and patients. Arguably, the success of B cell depletion with rituximab in open-label clinical trials, the approval of belimumab (which blocks B cell-activating factor (BAFF)) for use in patients with lupus nephritis in the USA and in difficult-to-treat patients with SLE in the UK and the recognition that clinical trial design can be improved have given some cause for hope. However, changes to therapies in current use and the development of new approaches are urgently needed. The results of the latest studies investigating the use of several new approaches to treating SLE are discussed in this Review, including: fully humanized anti-CD20 and anti-CD19 monoclonal antibodies; inhibition of tyrosine-protein kinase BTK; CD40 ligand blockade; interfering with the presentation of antigen to autoreactive T cells using a peptide approach; a receptor decoy approach using an analogue of Fcγ receptor IIB; dual blockade of IL-12 and IL-23; and inhibition of Janus kinases.
Blockade of interferon-γ normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. [2019]To assess the safety and immunologic impact of inhibiting interferon-γ (IFNγ) with AMG 811, a human IgG1 monoclonal antibody against IFNγ, in patients with systemic lupus erythematosus (SLE).
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]Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE).
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]To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.
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]Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. Obexelimab is a non-depleting anti-human CD19 mAb with an Fc region engineered to have high affinity for human FcγRIIb, thereby co-engaging BCR and FcγRIIb. To assess its ability to suppress B cell activation in vivo, we generated non-autoimmune-prone C57BL/6 (B6) and SLE-prone NZM 2328 (NZM) mice in which the human FcγRIIb extracellular domain was knocked into the mouse Fcgr2b locus (B6.hRIIb and NZM.hRIIb mice, respectively, the latter retaining features of SLE). XENP8206, a mAb which bears the same FcγRIIb-enhanced human Fc domain as does obexelimab but which recognizes murine CD19 rather than human CD19, inhibited in vitro BCR-triggered activation of B cells from both B6.hRIIb and NZM.hRIIb mice. Following administration of XENP8206 to B6.hRIIb or NZM.hRIIb mice, B cell numbers in the spleen and lymph nodes remained stable but became hyporesponsive to BCR-triggered activation for at least 14 days. These findings demonstrate proof-of-principle that pharmacologic co-engagement of BCR and human FcγRIIb inhibits B cell activation in non-autoimmune and SLE-prone hosts while preserving B cell numbers. These observations lay a strong foundation for clinical trials in human SLE with agents that co-engage BCR and FcγRIIb. Moreover, B6.hRIIb and NZM.hRIIb should serve as powerful in vivo models in the elucidation of the cellular and molecular underpinnings of the changes induced by BCR/FcγRIIb co-engagement.
Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. [2011]Engagement of the low-affinity Ab receptor FcγRIIb downregulates B cell activation, and its dysfunction is associated with autoimmunity in mice and humans. We engineered the Fc domain of an anti-human CD19 Ab to bind FcγRIIb with high affinity, promoting the coengagement of FcγRIIb with the BCR complex. This Ab (XmAb5871) stimulated phosphorylation of the ITIM of FcγRIIb and suppressed BCR-induced calcium mobilization, proliferation, and costimulatory molecule expression of human B cells from healthy volunteers and systemic lupus erythematosus (SLE) patients, as well as B cell proliferation induced by LPS, IL-4, or BAFF. XmAb5871 suppressed humoral immunity against tetanus toxoid and reduced serum IgM, IgG, and IgE levels in SCID mice engrafted with SLE or healthy human PBMC. XmAb5871 treatment also increased survival of mice engrafted with PBMC from a unique SLE patient. Unlike anti-CD20 Ab, coengagement of FcγRIIb and BCR complex did not promote B cell depletion in human PBMC cultures or in mice. Thus, amplification of the FcγRIIb inhibitory pathway in activated B cells may represent a novel B cell-targeted immunosuppressive therapeutic approach for SLE and other autoimmune diseases that should avoid the complications associated with B cell depletion.
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]Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. The aim of this study was to characterize B cell immunosuppression mediated by the Fc-engineered antibody, XmAb5871, which coengages FcγRIIb with the B cell antigen receptor (BCR) complex and that is currently in clinical development for the treatment of rheumatoid arthritis (RA). Because rheumatoid factor (RF) might interfere with the binding of XmAb5871 to FcγRIIb, we correlated RF titers with the potency of XmAb5871.
MEDI-551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for Sle1 and Human CD19. [2019]To evaluate treatment with MEDI-551, a humanized anti-human CD19 monoclonal antibody, in a model of autoimmunity involving mice transgenic (Tg) for Sle1 and human CD19 (hCD19).