Obexelimab for Multiple Sclerosis

Not currently recruiting at 52 trial locations

Overseen By Patient and Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Zenas BioPharma (USA), LLC

Disqualifiers: Primary progressive MS, Neuromyelitis optica, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called obexelimab, a humanized Fc-engineered monoclonal antibody against CD19, to evaluate its effectiveness and safety for people with relapsing multiple sclerosis (MS). MS occurs when the immune system mistakenly attacks the protective covering of nerves, leading to symptoms like fatigue, difficulty walking, and vision problems. Participants will receive either obexelimab or a placebo (a substance with no active drug) through an injection under the skin. Those diagnosed with relapsing MS who have experienced relapses or specific brain scan results might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that obexelimab is generally well-tolerated. In previous studies, patients experienced good results without major side effects. The data indicate that it does not significantly harm B cells, which are important white blood cells for the immune system.

Other studies have found that obexelimab, when injected under the skin, is well-absorbed and safe for people of different ethnic backgrounds. So far, no serious side effects have been reported, suggesting it is a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Obexelimab is unique because it targets CD19, a protein found on certain immune cells, which could help reduce inflammation in multiple sclerosis (MS). Unlike standard treatments for MS, which often focus on modulating the immune system broadly, Obexelimab offers a more targeted approach. Researchers are excited because this specificity might lead to fewer side effects and potentially more effective control of the disease. Plus, it's administered as a subcutaneous injection, which could be more convenient than some existing therapies that require intravenous infusion.

What evidence suggests that obexelimab might be an effective treatment for multiple sclerosis?

Research has shown that obexelimab, which participants in this trial may receive, could be a promising treatment for relapsing multiple sclerosis. One study demonstrated a 95% reduction in new brain lesions with obexelimab compared to a placebo. These lesions indicate inflammation in the brain, a common feature of multiple sclerosis. Obexelimab targets a protein on B cells, immune cells involved in the disease. By blocking these cells, obexelimab may help reduce symptoms and prevent flare-ups. This treatment has also proven effective in other immune-related conditions, making it a potential option for multiple sclerosis. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for people with relapsing multiple sclerosis (RMS), either relapsing-remitting or secondary progressive with flare-ups. Participants should have an EDSS score of 5.5 or less, not be able to bear children or follow birth control guidelines, and must have had at least one MS flare-up in the last year or a new brain lesion recently.

Inclusion Criteria

I have been diagnosed with RMS based on the 2017 McDonald criteria.

An EDSS of ≤ 5.5 at the Screening Visit

I am not able to have children or I agree to follow birth control advice.

Exclusion Criteria

Has > 20 Gd+ lesions on brain MRI at screening

I have been diagnosed with neuromyelitis optica spectrum disorder.

My condition worsened in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Randomized Placebo-Controlled Period (Part A)

Participants receive weekly subcutaneous injections of obexelimab or placebo

12 weeks

Weekly visits (in-person)

Open-Label Period (Part B)

All participants receive weekly subcutaneous injections of obexelimab

12 weeks

Weekly visits (in-person)

Open-Label Extension (Part C)

Participants continue to receive weekly subcutaneous injections of obexelimab

52 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

1 visit (in-person), additional visits every 12 weeks if needed

What Are the Treatments Tested in This Trial?

Interventions

• Obexelimab

Trial Overview The MoonStone study is testing the effectiveness and safety of a medication called obexelimab for treating RMS. Patients will randomly receive either obexelimab or a placebo to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: Obexelimab Experimental Treatment 1 Intervention

Obexelimab will be administered as a subcutaneous injection for 76 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo will be administered as a subcutaneous injection for 12 weeks

Who Is Running the Clinical Trial?

Zenas BioPharma (USA), LLC

Lead Sponsor

Trials

8

Recruited

760+

Published Research Related to This Trial

Alemtuzumab significantly reduced the rate of disability accumulation and relapse in early relapsing-remitting multiple sclerosis compared to interferon beta-1a, with a 9.0% disability accumulation rate versus 26.2% for interferon (P<0.001).

While alemtuzumab showed greater efficacy, it was associated with serious adverse events, including a higher incidence of autoimmune conditions like thyroid disorders (23% vs. 3%) and immune thrombocytopenic purpura (3% vs. 1%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. Coles, AJ., Compston, DA., Selmaj, KW., et al.[2022]

Monoclonal antibodies targeting CD20-positive B cells have shown significant efficacy in treating multiple sclerosis (MS), offering a promising approach to reduce relapse activity and disease progression.

Recent clinical trials have highlighted the effectiveness of these B cell-depleting therapies compared to traditional treatments, indicating a shift towards more targeted therapies in managing MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the treatment of multiple sclerosis: emergence of B-cell-targeted therapies. Nguyen, AL., Gresle, M., Marshall, T., et al.[2023]

Ocrelizumab (OCR) effectively alters the immune profile in patients with relapsing-remitting multiple sclerosis (RR-MS), particularly increasing naive CD4+ T cells and decreasing certain effector memory CD4+ and CD8+ T cell subsets associated with disease activity.

The study highlights the potential role of effector memory T cells, especially CD8+ T cells expressing CCR5, in the disease's pathophysiology and OCR's mechanism of action, suggesting that these immune changes may correlate with clinical outcomes in RR-MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Profiling Reveals the T-Cell Effect of Ocrelizumab in Early Relapsing-Remitting Multiple Sclerosis. Garcia, A., Dugast, E., Shah, S., et al.[2023]

Novel biologics for multiple sclerosis (MS), including monoclonal antibodies and small molecules, target specific immune processes, showing promise in improving treatment efficacy compared to traditional therapies like interferon beta and glatiramer acetate.

These new treatments, such as natalizumab and ocrelizumab, not only aim to reduce disease activity but also come with varying safety profiles and potential adverse reactions, highlighting the need for careful monitoring in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New biological agents in the treatment of multiple sclerosis. Buc, M.[2018]

In a study of 82 multiple sclerosis patients treated with ocrelizumab (OCR), the drug was found to be effective in reducing relapse rates from 1.33 to 0.15 in those with relapsing-remitting MS, while maintaining stable disability scores across different ethnic groups.

OCR was generally well-tolerated, with 50% of patients experiencing at least one adverse event; however, there were notable cases of severe babesiosis and other serious conditions, highlighting the importance of considering geographic risk factors when initiating treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab initiation in a diverse multiple sclerosis population. Coban, H., Germaine, S., Dimaandal, I., et al.[2021]

In phase 3 trials, patients with relapsing-remitting multiple sclerosis treated with alemtuzumab showed significant improvements in quality of life (QoL) across multiple measures, including physical, mental, and emotional aspects, sustained through Year 2.

Alemtuzumab demonstrated greater QoL improvements compared to subcutaneous interferon beta-1a at all time points, indicating its superior efficacy in enhancing the overall well-being of patients, regardless of their treatment history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis. Arroyo González, R., Kita, M., Crayton, H., et al.[2018]

Monoclonal antibody therapies, like natalizumab and alemtuzumab, have shown significant effectiveness in reducing disease activity and disability in relapsing-remitting multiple sclerosis, based on clinical studies.

Each monoclonal antibody has a unique mechanism of action and administration schedule, making it essential to evaluate them individually when choosing the best treatment for MS patients, considering both benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes. Lycke, J.[2023]

Monoclonal antibodies (mAbs) are a promising and specific treatment strategy for multiple sclerosis (MS), targeting selective molecules to potentially improve clinical outcomes.

The four mAbs currently under investigation (natalizumab, rituximab, alemtuzumab, and daclizumab) have distinct mechanisms of action that may influence immune cell activity and central nervous system inflammation, but they also carry notable risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in MS: mechanisms of action. Bielekova, B., Becker, BL.[2009]

The humanized anti-CD11/CD18 monoclonal antibody Hu23F2G was well-tolerated in a phase I study involving 24 patients with multiple sclerosis, with only a few adverse effects reported, including urinary tract infections and gingivitis.

Hu23F2G effectively saturated CD11/CD18 on leukocytes at doses of 0.2 mg/kg and above, leading to a significant reduction in leukocyte migration, although the study did not assess its clinical efficacy, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis. Bowen, JD., Petersdorf, SH., Richards, TL., et al.[2017]

Citations

1. sciencedirect.com sciencedirect.com/topics/immunology-and-microbiology/xmab5871

Xmab5871 - an overview | ScienceDirect Topics An antibody that binds both CD19 and the inhibitory immunoglobulin receptor FcγRIIb (Obexelimab or XmAb5871) results in inhibition but not depletion of B cells.

2. investors.zenasbio.com investors.zenasbio.com/news-releases/news-release-details/zenas-biopharma-announces-positive-results-phase-2-moonstone

Release Details Obexelimab met primary endpoint with a 95% relative reduction in new gadolinium (Gd)-enhancing T1 lesions compared with placebo, ...

3. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/obexelimab-zenas-biopharma-usa-multiple-sclerosis-likelihood-of-approval/

Obexelimab by Zenas BioPharma (USA) for Multiple ... It is a humanized monoclonal antibody that targets the antigen CD19 and co-engages CD32b (Fc gammaRIIb). The drug candidate is developed ...

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. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06564311

A Study of Obexelimab in Patients With Relapsing Multiple ... This study aims to examine the efficacy and safety of obexelimab in participants with relapsing multiple sclerosis.