Imvotamab for Lupus

Recruiting at 7 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

17 Participants Needed

Trial Summary

What is the purpose of this trial?

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 therapies. Participants will be given imvotamab through a vein (i.e., intravenously).

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.

What data supports the idea that Imvotamab for Lupus is an effective drug?

The available research does not provide specific data on Imvotamab for Lupus. Instead, it focuses on other treatments like rituximab and belimumab. These studies show that rituximab, a drug similar to Imvotamab, can help reduce symptoms in lupus patients by targeting B cells, which are part of the immune system. However, the effectiveness of rituximab has not been proven in all trials, and combining it with belimumab might improve results. Without direct data on Imvotamab, we can't confirm its effectiveness for Lupus based on the information provided. ^{1 2 3 4 5}

What safety data is available for Imvotamab (IGM 2323) in treating lupus?

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 sifalimumab, ustekinumab, rituximab, and amiselimod for systemic lupus erythematosus (SLE). ^{6 7 8 9 10}

Is the drug Imvotamab a promising treatment for Lupus?

Imvotamab, also known as IGM 2323, is a promising drug for treating Lupus because it targets B cells, which play a key role in the disease. By focusing on these cells, Imvotamab could help reduce the symptoms and damage caused by Lupus. ^{2 7 11 12 13}

Research Team

Rebecca Kunder

Principal Investigator

IGM Biosciences

Eligibility Criteria

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.

I am 18 years old or older.

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

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]

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]

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]

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]

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]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Long-term follow-up of patients with refractory systemic lupus erythematosus during rituximab treatment]. [2015]

2. United States 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. [2022]

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

Intravenous immunoglobulin treatment of lupus nephritis. [2022]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study. [2015]

6. England 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. [2022]

7. England 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. [2022]

8. England 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). [2015]

9. England pubmed.ncbi.nlm.nih.gov

Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis. [2021]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the treatment of systemic lupus erythematosus. [2019]

12. 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]

13. New Zealand 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. [2022]