Imvotamab for Lupus

No longer recruiting at 8 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IGM Biosciences, Inc.

Must be taking: Immunosuppressives, Biologics

Must not be taking: Prednisone > 30 mg/day

Disqualifiers: Pregnancy, Neuropsychiatric disease, Lupus nephritis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing the safety and tolerability of a new treatment called imvotamab for individuals with severe systemic lupus erythematosus (SLE), a condition where the immune system attacks the body. Participants will receive the medication through an IV. This trial is best suited for those who have had lupus for at least 16 weeks, have highly active disease, and have not responded well to other treatments. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, it requires that your standard-of-care treatment remains at a stable dose up to Week 8.

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

Research shows that imvotamab may help treat certain conditions by targeting specific immune cells. However, limited safety information exists for imvotamab in lupus patients.

In animal studies, imvotamab successfully targeted and affected immune cells, suggesting potential effectiveness in humans. However, these results are not from human studies.

This study is in its early stages, focusing primarily on the treatment's safety and tolerability. Researchers are beginning to understand how the treatment might affect humans.

For those considering joining this trial, please note that safety and side effects are still under careful study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imvotamab is unique because it introduces a novel approach to treating lupus by targeting specific immune pathways with a monoclonal antibody. Unlike conventional treatments that mainly focus on suppressing the immune system generally, Imvotamab works by targeting specific cells responsible for the autoimmune response. Researchers are excited about this treatment because it has the potential to offer more precise management of lupus with fewer side effects, addressing the root cause of the disease more effectively than current options. Additionally, its intravenous administration allows for controlled delivery and potentially improved efficacy compared to oral medications.

What evidence suggests that imvotamab might be an effective treatment for lupus?

Research has shown that imvotamab, a type of antibody, can destroy certain immune cells called B cells, which often contribute to autoimmune diseases like lupus. In animal studies, this treatment effectively reached tissues, suggesting potential effectiveness in humans. Although human studies remain limited, imvotamab's mechanism offers hope for those with severe lupus who haven't improved with other treatments. Participants in this trial will receive imvotamab in a dose escalation format to evaluate its safety and effectiveness. ^{1 3 4 5 6}

Who Is on the Research Team?

Rebecca Kunder

Principal Investigator

IGM Biosciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with severe systemic lupus erythematosus (SLE) who haven't responded to treatments like methotrexate or belimumab. They should have active SLE and a high disease activity score but stable standard care doses up to Week 8. Not eligible if pregnant, breastfeeding, planning pregnancy soon, have severe kidney issues, take high-dose steroids, neuropsychiatric lupus complications, drug-induced lupus or recent severe anti-phospholipid syndrome.

Inclusion Criteria

During the Screening Period and up to Week 8, it is required that background standard-of-care treatment remain at a constant dosage.

My lupus is still active despite taking standard treatments for at least 3 months.

My lupus is very active, with a SLEDAI score of 10 or more.

Exclusion Criteria

Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the final dose of imvotamab.

I have severe lupus affecting my kidneys with low kidney function.

I have a brain or nerve condition related to lupus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imvotamab intravenously in a dose escalation format

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Imvotamab

Trial Overview The study tests the safety and effectiveness of Imvotamab in patients with serious SLE. Participants will receive Imvotamab intravenously while keeping their usual SLE medications constant to see how well it works when other therapies fail.

How Is the Trial Designed?

Group I: Imvotamab (Dose Escalation) Experimental Treatment 1 Intervention

Imvotamab administered intravenously

Who Is Running the Clinical Trial?

IGM Biosciences, Inc.

Lead Sponsor

Trials

10

Recruited

520+

Published Research Related to This Trial

In a study of 85 systemic lupus erythematosus (SLE) patients treated with rituximab, 46.8% achieved a complete response and 34.2% a partial response, indicating significant clinical improvement over an average follow-up of 9.6 months.

The treatment showed a favorable safety profile, with only one infusion reaction leading to discontinuation and a reported infection rate of 19.5 per 100 patient years, including six severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID). Witt, M., Grunke, M., Proft, F., et al.[2015]

Rituximab therapy for systemic lupus erythematosus (SLE) showed significant improvements in disease activity, as evidenced by decreased scores on the SLEDAI and BILAG indices, along with reduced urine protein levels and lower prednisolone doses in 21 studies (2 randomized controlled trials and 19 observational studies).

The adverse effects of rituximab were manageable with proper dosing, indicating that it can be a safe option for treating refractory lupus, although further research is needed to fully understand its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis. Lan, L., Han, F., Chen, JH.[2021]

In a study of 10 lupus nephritis patients treated with rituximab, 80% achieved partial remission within 2 months, with 50% later reaching complete remission, indicating the treatment's efficacy in managing this condition.

B cell depletion was well tolerated and associated with significant decreases in T cell activation markers, suggesting that B cells may play a role beyond just producing autoantibodies in the disease process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Sfikakis, PP., Boletis, JN., Lionaki, S., et al.[2022]

Monoclonal antibodies (mAbs) targeting B cells, such as rituximab and epratuzumab, have shown high efficacy in treating systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis and neuropsychiatric symptoms.

Newly developed mAbs, including ofatumumab and GA-101, demonstrate strong cytotoxic effects against B cells, while therapies targeting proinflammatory cytokines like TNF-alpha and IL-6, as well as the complement inhibitor eculizumab, offer promising avenues for SLE treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the treatment of systemic lupus erythematosus. Robak, E., Robak, T.[2019]

In a phase 3 study involving 516 patients with active systemic lupus erythematosus (SLE), ustekinumab did not show superior efficacy compared to placebo, with similar response rates at week 52 (44% for ustekinumab vs. 56% for placebo).

The study was discontinued due to lack of efficacy, but there were no safety concerns, and the adverse events reported were consistent with ustekinumab's known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus. van Vollenhoven, RF., Kalunian, KC., Dörner, T., et al.[2022]

In a study of seven patients with treatment-resistant membranous and membranoproliferative lupus nephritis, all patients showed a beneficial response to high-dose intravenous immunoglobulin (IVIg) therapy, indicating its potential efficacy for this condition.

Patients experienced significant reductions in proteinuria and improvements in plasma albumin levels after IVIg treatment, suggesting that IVIg may help manage kidney-related symptoms in lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin treatment of lupus nephritis. Levy, Y., Sherer, Y., George, J., et al.[2022]

In a phase IIb study involving 431 adults with moderate to severe systemic lupus erythematosus (SLE), sifalimumab showed significant efficacy, with higher response rates compared to placebo (up to 59.8% for the highest dose) at week 52.

While sifalimumab demonstrated promising improvements in various measures of disease activity, it was associated with a slightly higher incidence of serious adverse events and more frequent herpes zoster infections compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Khamashta, M., Merrill, JT., Werth, VP., et al.[2022]

In a study of 116 patients with refractory lupus, 62.9% achieved a response after six months of treatment with rituximab, indicating its effectiveness, especially in severe cases.

Rituximab was associated with an acceptable safety profile, although 38.1% of patients relapsed after the first infusion, and serious infections occurred at a rate of 12.6 per 100 patient-years, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study. Fernández-Nebro, A., de la Fuente, JL., Carreño, L., et al.[2015]

SM03, a novel monoclonal antibody targeting CD22 on B lymphocytes, was well tolerated in a phase I study involving 29 patients with systemic lupus erythematosus (SLE), showing no serious drug-related adverse events.

The treatment demonstrated potential efficacy, particularly in patients with moderate-to-severe disease activity, with pharmacokinetic data indicating a steady increase in drug exposure without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Pharmacodynamics and Preliminary Observations for Clinical Activity and Safety of Multiple Doses of Human Mouse Chimeric Anti-CD22 Monoclonal Antibody (SM03) in Chinese Patients with Systemic Lupus Erythematosus. Zhao, Q., Chen, X., Li, J., et al.[2022]

Rituximab (RTM) therapy was found to be highly effective in treating systemic lupus erythematosus (SLE) in 97 patients who were resistant to standard treatments, with 82% showing clinical improvement over an 18-month follow-up period.

The therapy was well-tolerated, with no significant increase in the risk of infections or adverse reactions, and patients who maintained complete B cell depletion had a higher rate of complete response compared to those with B cell recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term follow-up of patients with refractory systemic lupus erythematosus during rituximab treatment]. Tsanian, MÉ., Solov'ev, SK., Torgashina, AV., et al.[2015]

The BEAT Lupus trial is a phase II clinical study designed to evaluate the safety and efficacy of belimumab administered after rituximab in patients with systemic lupus erythematosus (SLE), aiming to reduce anti-double stranded DNA (anti-dsDNA) antibody levels over 52 weeks.

This study could potentially provide a new treatment strategy for SLE patients who do not respond to conventional therapies, as belimumab targets B cell activating factor (BAFF), which may enhance the effects of rituximab and prolong disease remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial. Jones, A., Muller, P., Dore, CJ., et al.[2022]

Amiselimod, an oral medication for systemic lupus erythematosus (SLE), was generally well tolerated in a phase Ib trial with 17 participants, showing no serious adverse events or significant cardiac effects.

The treatment led to a decrease in anti-double stranded-DNA antibodies and improved SLE disease activity in some patients, suggesting potential efficacy, although low lymphocyte counts were noted as a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study. Tanaka, Y., Kondo, K., Ichibori, A., et al.[2021]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06041568

NCT06041568 | A Study of Imvotamab in Severe Systemic ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with severe systemic lupus erythematosus who have failed prior ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496724162917

Imvotamab for Refractory Autoimmune Disease Patients Imvotamab effectively kills peripheral B cells isolated from AI patients. Moreover, in a non-human primate model, a CD20xCD3 IgM TCE can penetrate tissues to ...

3. delta.larvol.com delta.larvol.com/Products/?ProductId=41459c52-83e7-4d44-bb5b-ca28ddfa307c

imvotamab (IGM-2323) / IGM Biosciences - "Imvotamab (CD20 x CD3) trials in rheumatoid arthritis, systemic lupus erythematosus and myositis ongoing; initial clinical data expected by mid-2025....IGM ...

4. biospace.com biospace.com/igm-biosciences-announces-fda-clearance-to-begin-clinical-studies-of-imvotamab-in-lupus-and-rheumatoid-arthritis

IGM Biosciences Announces FDA Clearance to Begin ... The primary outcome measure of the Phase 1b SLE and RA clinical trials will be the safety, tolerability, pharmacokinetics, pharmacodynamics and ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06041568/a-study-of-imvotamab-in-severe-systemic-lupus-erythematosus

A Study of Imvotamab in Severe Systemic Lupus ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with severe systemic lupus erythematosus who ...

6. withpower.com withpower.com/trial/phase-1-lupus-erythematosus-systemic-7-2023-c1dba

Imvotamab for Lupus · Info for Participants The provided research does not contain any safety data for Imvotamab (IGM 2323) in the treatment of lupus. The studies listed focus on other treatments such as ...