Afimetoran for Lupus

Not currently recruiting at 421 trial locations

Overseen By Nazanin Firooz, Site 0164

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Disqualifiers: Severe lupus nephritis, Neuropsychiatric lupus, Mixed connective tissue disease, Antiphospholipid syndrome

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the efficacy and safety of Afimetoran for individuals with active Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks the body. Participants will receive either Afimetoran, a TLR 7/8 antagonist, or a placebo to compare outcomes. The trial seeks individuals diagnosed with lupus who have specific lupus-related antibodies and experience joint pain or rashes. Those with severe kidney issues or certain other lupus-related conditions are not eligible. The trial includes a long-term extension to gather more data and allow those on placebo to try Afimetoran. As a Phase 2 trial, the research focuses on evaluating 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 this trial's treatments are likely to be safe?

Research shows that Afimetoran is a new treatment targeting specific parts of the immune system. Taken orally, it blocks Toll-like receptors 7 and 8. Earlier studies found that patients generally tolerated Afimetoran well. These studies did not identify any major safety concerns, suggesting Afimetoran could be a safe option for treating lupus. However, as the research remains in the middle stages, more information is needed to fully understand its long-term safety. Prospective trial participants should know that this treatment is still under study. Current evidence suggests it is safe for human use, with no severe side effects reported. ^{1 2 3 4 5}

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

Unlike the standard treatments for lupus, which often include corticosteroids and immunosuppressants, Afimetoran targets the body's immune response in a unique way. It acts on the interferon pathway, a key player in the inflammation process associated with lupus. Researchers are excited about Afimetoran because it has the potential to more precisely modulate the immune system, potentially reducing side effects compared to current therapies. Plus, with multiple dosing options being explored, there's hope for tailoring the treatment to individual patient needs, providing a more personalized approach to managing lupus.

What evidence suggests that Afimetoran might be an effective treatment for Lupus?

Research has shown that Afimetoran could be a promising treatment for Systemic Lupus Erythematosus (SLE). It blocks specific parts of the immune system, known as Toll-like receptors 7 and 8, which play a role in lupus. In studies with mice, Afimetoran reduced disease symptoms, even when other treatments failed. Early human trials have demonstrated that Afimetoran is generally well-tolerated, with most participants not experiencing severe side effects. This trial will test different doses of Afimetoran to assess its effectiveness and safety for people with lupus. These initial results suggest Afimetoran might be effective for people with lupus, but further research is necessary to confirm this. ^{1 2 3 4 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for people with active Systemic Lupus Erythematosus (SLE) who meet specific criteria, including a positive test for certain lupus-related antibodies and a minimum disease activity score. It's not open to those with severe lupus nephritis, Antiphospholipid Syndrome, unstable neuropsychiatric symptoms, or if their main diagnosis isn't SLE.

Inclusion Criteria

I tested positive for lupus-related antibodies.

My lupus is active, with a score of 6 or more, and affects my joints or skin.

I was diagnosed with lupus over 12 weeks ago and meet the SLICC criteria.

Exclusion Criteria

I have been diagnosed with Antiphospholipid Syndrome.

I have been diagnosed with severe active lupus nephritis.

I do not have active or unstable mental health issues due to lupus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Afimetoran or placebo to evaluate effectiveness, safety, and tolerability

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants initially randomized to placebo may receive Afimetoran for additional long-term safety and efficacy data

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Afimetoran
• BMS-986256 (Oral)
• Placebo

Trial Overview

The study tests the effectiveness and safety of Afimetoran versus a placebo in individuals with active SLE. Participants will be randomly assigned to receive either Afimetoran or a placebo to compare outcomes and gather long-term data on Afimetoran's performance.

How Is the Trial Designed?

Group I: Afimetoran: Dose 3 Experimental Treatment 1 Intervention

Group II: Afimetoran: Dose 2 Experimental Treatment 1 Intervention

Group III: Afimetoran: Dose 1 Experimental Treatment 1 Intervention

Group IV: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

M5049 is a newly discovered dual inhibitor of TLR7 and TLR8 that shows potent and selective activity in blocking immune responses linked to autoimmune diseases, particularly lupus, as demonstrated in several murine models.

This compound not only effectively inhibits TLR7/8 activity but also preferentially accumulates in tissues, suggesting it could be a promising therapeutic option for a range of autoimmune conditions beyond those traditionally associated with TLR7/8 activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of M5049: A Novel Selective Toll-Like Receptor 7/8 Inhibitor for Treatment of Autoimmunity. Vlach, J., Bender, AT., Przetak, M., et al.[2021]

BMS-986126 is a highly selective inhibitor of IRAK4 that effectively suppresses MyD88-dependent immune responses, showing promise in reducing cytokine production from various TLR agonists in mouse models.

In lupus models, BMS-986126 not only inhibited pathogenic responses but also demonstrated potential for steroid-sparing effects when used in combination with prednisolone, indicating its therapeutic benefit for lupus treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity. Dudhgaonkar, S., Ranade, S., Nagar, J., et al.[2018]

In a study of prediseased BXSB male and female B cells, male B cells showed a stronger response to TLR-7 ligands, especially when the B cell receptor (BCR) was also activated, leading to increased IL-6 secretion.

The research indicates that while TLR-7 antagonists could be potential treatments for lupus, their effectiveness may be compromised by the simultaneous activation of the BCR, which could promote the survival of autoreactive B cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engagement of the B cell receptor for antigen differentially affects B cell responses to Toll-like receptor-7 agonists and antagonists in BXSB mice. Layer, T., Steele, A., Goeken, JA., et al.[2021]

The small-molecule compound FC-99 effectively inhibits key inflammatory markers and the activation of dendritic cells, which are crucial in the immune response related to systemic lupus erythematosus (SLE).

In murine models of lupus, FC-99 demonstrated significant efficacy in reducing disease symptoms, suggesting it could be a promising candidate for treating SLE in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel small molecule compound possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR7 signaling pathway and alleviates the development of SLE. Gao, S., Yuan, L., Li, C., et al.[2018]

A new compound, E6742, effectively blocks the activation of Toll-like receptors 7 and 8 (TLR7/8), which are involved in the progression of lupus, by binding specifically to their structure, suggesting a novel therapeutic approach for the disease.

In mouse models of lupus, E6742 demonstrated significant therapeutic potential by suppressing autoantibody levels and preventing organ damage when administered after disease onset, indicating its efficacy in managing lupus symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel Toll-like receptor 7/8-specific antagonist E6742 ameliorates clinically relevant disease parameters in murine models of lupus. Ishizaka, ST., Hawkins, L., Chen, Q., et al.[2023]

Oligodeoxyribonucleotides modified to act as TLR7 and TLR9 antagonists effectively inhibited immune responses in both mouse and human cell cultures, demonstrating their potential to suppress unwanted immune activation.

In mouse models, these antagonists provided dose-dependent inhibition of immune responses for several days, suggesting they could be useful in treating inflammatory and autoimmune diseases linked to excessive TLR activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligodeoxyribonucleotide-based antagonists for Toll-like receptors 7 and 9. Wang, D., Bhagat, L., Yu, D., et al.[2009]

In a study using lupus-prone NZBW/F1 mice, an antagonist targeting TLR7, 8, and 9 significantly reduced serum levels of autoantibodies and improved kidney health, indicating its potential efficacy in treating lupus.

The antagonist treatment also led to a favorable shift in inflammatory markers, decreasing pro-inflammatory cytokines like IL-12 and IL-1β while increasing the anti-inflammatory cytokine IL-10, suggesting a mechanism for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel antagonist of Toll-like receptors 7, 8 and 9 suppresses lupus disease-associated parameters in NZBW/F1 mice. Zhu, FG., Jiang, W., Bhagat, L., et al.[2013]

The study indicates that type I interferons (IFN-α) are key drivers of lupus disease progression, as deleting the Ifnb gene did not alter disease outcomes in NZB mice.

Long-term treatment with an anti-IFN-α/β receptor antibody significantly reduced disease symptoms and improved survival in BXSB mice, especially when started early in the disease, suggesting potential for this treatment approach in human lupus and other autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-IFN-α/β receptor antibody treatment ameliorates disease in lupus-predisposed mice. Baccala, R., Gonzalez-Quintial, R., Schreiber, RD., et al.[2021]

Two compounds, AT791 and E6446, effectively inhibit Toll-like receptors (TLR) 7 and 9, which are involved in stimulating immune responses in lupus patients, showing potential as therapeutic agents.

In mouse models of lupus, E6446 slowed the development of certain autoimmune markers, although it did not significantly affect kidney damage or survival, indicating a need for further research on its overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Lamphier, M., Zheng, W., Latz, E., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12198911/

Safety, Tolerability, Efficacy, Pharmacokinetics, and ...

Afimetoran is an investigational, first‐in‐class, orally bioavailable, selective small molecule inhibitor of Toll‐like receptors (TLRs) 7 and 8.

2.

ard.bmj.com

ard.bmj.com/content/82/Suppl_1/1245.2

AB0132 AFIMETORAN (BMS-986256), AN EQUIPOTENT ...

Conclusion Afimetoran, either alone or in combination with prednisolone, showed efficacy in NZB/W mice with moderate disease. It also reversed the resistance of ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04895696

NCT04895696 | A Study Evaluating the Efficacy and Safety ...

The purpose of this study is to evaluate the effectiveness, safety and tolerability of Afimetoran in participants with active Systemic Lupus Erythematosus (SLE) ...

4.

ard.bmj.com

ard.bmj.com/content/83/Suppl_1/1110

POS0551 PHARMACODYNAMIC EFFECTS AND ...

Afimetoran may have therapeutic potential for CLE, given the involvement of TLRs 7/8 in disease pathobiology of the closely related SLE [2]. A phase 1b, ...

5.

bmsstudyconnect.com

bmsstudyconnect.com/br/en/clinical-trials/NCT04895696.html

A Study Evaluating the Efficacy and Safety of Afimetoran ...

The purpose of this study is to evaluate the effectiveness, safety and tolerability of Afimetoran in participants with active Systemic Lupus ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40568766/

A Phase 1b Randomized, Double-Blind, Placebo ...

These findings support afimetoran's potential as a once daily oral treatment for patients with CLE and suggest a possibly substantial therapeutic benefit, ...