Imvotamab for Rheumatoid Arthritis

No longer recruiting at 26 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IGM Biosciences, Inc.

Must not be taking: Cell depleting, JAK inhibitors

Disqualifiers: Other autoimmune diseases, Psoriatic arthritis, others

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 tests a new treatment called imvotamab (also known as IGM 2323) to determine its safety and tolerability for people with moderate to severe rheumatoid arthritis (RA), a condition that causes joint pain and swelling. Participants will receive either imvotamab or a placebo (a look-alike substance with no active drug) through an IV. It suits those who have tried other RA treatments without success and currently have at least six swollen and six tender joints. As a Phase 1 trial, this 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 need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot have received certain RA therapies like cell depleting therapies, specific tsDMARDs, or immunomodulatory bDMARDs within 3 months or 5 half-lives before starting the study treatment. If you're on oral corticosteroids, you must be on a stable dose of 10 mg/day or less of prednisone for at least 2 weeks before the study.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but you must not have taken certain RA therapies like cell depleting therapies or specific immunomodulatory drugs within 3 to 6 months before starting the study treatment. If you're on oral corticosteroids, you must be on a stable dose of 10 mg/day or less of prednisone for at least 2 weeks before the study.

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

Research shows that imvotamab remains in the early stages of testing for rheumatoid arthritis, and specific safety information for this use is not yet available. Earlier animal studies demonstrated that a compound similar to imvotamab effectively reached tissues, which is promising. However, as this is an early-stage study, the main goal is to determine its safety and tolerability in humans. Researchers closely monitor treatments in this phase for any side effects. Although detailed safety information for humans is not yet available, ensuring safety remains a top priority during this testing phase. ^{1 2 3 4 5}

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

Imvotamab is unique because it targets rheumatoid arthritis in a novel way. While most treatments for this condition, like methotrexate or TNF inhibitors, focus on suppressing the immune response broadly, Imvotamab is designed to work more precisely. It uses a specific mechanism of action that targets and modulates particular pathways involved in the inflammation process. Researchers are excited about its potential to offer more effective relief with potentially fewer side effects, thanks to its targeted approach.

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

Research shows that imvotamab, which participants in this trial may receive, may help treat rheumatoid arthritis. Studies have found that imvotamab can target and remove certain immune cells involved in this condition. Compared to rituximab, a common treatment, imvotamab proved more effective. Although data remains limited, these early results suggest that imvotamab could be a strong option for people who haven't had success with other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Eric Humke, MD

Principal Investigator

IGM Biosciences

Are You a Good Fit for This Trial?

Adults over 18 with moderate to severe rheumatoid arthritis who haven't responded well to at least two different biologic or targeted synthetic DMARDs. Participants should have active disease, shown by a certain number of swollen and tender joints and high inflammation markers in blood tests. They shouldn't have other autoimmune diseases (except secondary Sjögren's syndrome) or be on high doses of steroids.

Inclusion Criteria

I have been diagnosed with RA for over a year.

I tested positive for ACPA and/or RF.

I have tried specific arthritis medications without success.

Exclusion Criteria

I have taken specific immune system targeting drugs less than 3 months ago.

I have an autoimmune disease other than RA, or my RA has severe complications.

I have taken specific RA medications less than 3 months ago or before their half-lives expired.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imvotamab or placebo intravenously in dose escalation cohorts

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 trial is testing the safety and effects of Imvotamab, an experimental medication for rheumatoid arthritis, compared to a placebo. The drug or placebo is given intravenously. The goal is to see if Imvotamab can help people who didn't get better with previous treatments.

How Is the Trial Designed?

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

Imvotatmab administered intravenously

Group II: PBO IV Placebo Group 1 Intervention

Placebo administered intravenously

Who Is Running the Clinical Trial?

IGM Biosciences, Inc.

Lead Sponsor

Trials

10

Recruited

520+

Published Research Related to This Trial

In the ARISE trial involving 13 active rheumatoid arthritis patients, rituximab treatment led to nearly complete depletion of circulating B cells, but this did not directly correlate with clinical improvement, as only 7 out of 13 patients showed significant response after 6 months.

While rituximab reduced synovial B cells, the decrease was not as pronounced as in circulation, suggesting that additional mechanisms beyond B cell depletion, such as changes in B cell function or cytokine production, may contribute to the drug's efficacy in treating rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Kavanaugh, A., Rosengren, S., Lee, SJ., et al.[2018]

Namilumab, a monoclonal antibody targeting GM-CSF, showed significant efficacy in reducing disease activity in rheumatoid arthritis patients who did not respond adequately to methotrexate or TNF inhibitors, with a notable improvement in the Disease Activity Score (DAS28-CRP) at week 12.

The treatment was well-tolerated, with no serious infections reported, although one serious adverse event (myocardial infarction) occurred in the highest dose group; overall, the safety profile was acceptable over the 12-week study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of namilumab, a human monoclonal antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) ligand in patients with rheumatoid arthritis (RA) with either an inadequate response to background methotrexate therapy or an inadequate response or intolerance to an anti-TNF (tumour necrosis factor) biologic therapy: a randomized, controlled trial. Taylor, PC., Saurigny, D., Vencovsky, J., et al.[2020]

A single course of rituximab combined with methotrexate significantly improved physical function in patients with active rheumatoid arthritis over a 2-year period, with 45% of patients completing the follow-up without further treatment compared to only 15% in the placebo group.

Patients receiving rituximab + methotrexate reported greater improvements in disability scores, with 68% showing clinically meaningful changes after 1 year, highlighting the efficacy of this treatment combination compared to other regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years. Strand, V., Balbir-Gurman, A., Pavelka, K., et al.[2015]

Rituximab, a chimeric monoclonal antibody targeting the CD20 molecule on B-cells, has shown efficacy in treating rheumatoid arthritis, indicating its potential as a therapeutic option for this condition.

Recent evidence suggests that rituximab is generally safe for use in rheumatoid arthritis patients, although monitoring for potential side effects is still important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rituximab treatment of rheumatoid arthritis: new evidence]. Nasonov, EL.[2018]

Most rheumatologists (79%) reported that treatment-altering liver function abnormalities in rheumatoid arthritis patients treated with methotrexate occurred in less than 5% of cases, indicating that serious adverse events are relatively rare.

A significant number of rheumatologists (41%) believe that current liver function monitoring guidelines for methotrexate should be revised, with 59% supporting more frequent monitoring every 3-4 months, suggesting a potential shift towards less stringent monitoring protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring by rheumatologists for methotrexate-, etanercept-, infliximab-, and anakinra-associated adverse events. Yazici, Y., Erkan, D., Paget, SA.[2015]

A long-term safety evaluation of rituximab in 3194 patients with moderate-to-severe rheumatoid arthritis over 9.5 years showed stable rates of serious adverse events and infections, comparable to those receiving placebo plus methotrexate.

The study found no increased risk of malignancy or significant adverse events with prolonged rituximab exposure, indicating that it is generally well tolerated even after multiple treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients. van Vollenhoven, RF., Emery, P., Bingham, CO., et al.[2021]

In a study involving 15,132 patients with rheumatoid arthritis, adalimumab was found to have a well-established safety profile, with serious infections occurring at a low rate of 4.7 events per 100 patient-years and no significant laboratory abnormalities compared to placebo.

The analysis also indicated that pregnancy outcomes for women exposed to adalimumab were similar to those of unexposed women with rheumatoid arthritis and healthy women, with no increased risk of major birth defects or spontaneous abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Burmester, GR., Landewé, R., Genovese, MC., et al.[2022]

Rituximab, an anti-CD20 antibody, is an effective treatment for rheumatoid arthritis, significantly reducing joint destruction and improving clinical outcomes in patients who did not respond to TNF-inhibitors, based on the REFLEX study involving patients receiving 1000 mg Rituximab at 2-week intervals.

The treatment is generally well tolerated, with infusion reactions being the most common side effect (up to 35%), which can be mitigated by steroid premedication, although there is a slightly increased risk of serious infections compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-CD20 therapy in rheumatoid arthritis]. Roll, P., Tony, HP.[2021]

The study demonstrated that radiolabeled ¹²⁴I-rituximab can effectively visualize CD20 antigen expression in patients with rheumatoid arthritis, with detectable targeting in 4 out of 5 patients, indicating its potential utility in diagnosing and monitoring inflammation.

The imaging revealed CD20 positive B-cell infiltration in some joints that appeared clinically normal, suggesting that B-cell presence may not always correlate with visible inflammation, highlighting the need for further research to understand its clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD20 antigen imaging with ¹²⁴I-rituximab PET/CT in patients with rheumatoid arthritis. Tran, L., Huitema, AD., van Rijswijk, MH., et al.[2019]

Intravenous gammaglobulin has been linked to the treatment of dermatomyositis/polymyositis, suggesting its potential role in managing this autoimmune disease.

New therapies such as the immunosuppressant FK-506 and innovative approaches like medical arthroscopy for removing disease triggers are emerging, indicating a shift towards more targeted and effective treatments for autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel immunomodulating and immunotherapies, and novel therapies and strategies for inflammatory arthropathy. Trentham, DE.[2019]

In a comprehensive analysis of 65,099 patient-years of tocilizumab (TCZ) exposure, the rates of serious adverse events (SAEs) reported in postmarketing data were found to be similar to those observed in clinical trials and external comparator populations, indicating consistent safety profiles across different settings.

The study highlights that the rates of specific SAEs, such as serious hepatic events and myocardial infarctions, were comparable to those seen in anti-tumor necrosis factor (aTNF) treated rheumatoid arthritis patients, suggesting that TCZ's safety profile is in line with existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. Curtis, JR., Perez-Gutthann, S., Suissa, S., et al.[2019]

In a study of 208 rheumatoid arthritis (RA) patients, it was found that those with a low frequency of CD27+ memory B cells had a greater clinical response to rituximab (RTX), suggesting that this B cell subset may serve as a predictor for treatment efficacy.

The research indicated that CD27+ memory B cells were decreased in RA patients compared to healthy controls, and their levels correlated with serum B cell activation biomarkers, highlighting a potential B cell-driven subtype of RA that responds better to B cell depletion therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Sellam, J., Rouanet, S., Hendel-Chavez, H., et al.[2017]

In a study of 338 rheumatoid arthritis patients, rituximab (RTX) combined with methotrexate (MTX) showed similar efficacy to RTX alone after 52 and 104 weeks, indicating that both treatment options effectively reduce disease activity.

The safety profile of RTX was good, with 42% of patients experiencing adverse events, mostly mild to moderate, and comparable rates of severe adverse events between the RTX and RTX-MTX groups, suggesting that adding MTX does not significantly increase risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: results from the GISEA register. Sebastiani, M., Anelli, MG., Atzeni, F., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06087406

A Phase 1b Study of Imvotamab in Moderate to Severe ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with moderate to severe rheumatoid arthritis who have failed ...

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

POS1062 THERAPEUTIC POTENTIAL OF IMVOTAMAB, A ... 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 'Interim data from the Phase 1b studies of imvotamab in rheumatoid arthritis ... - P1 | "Imvotamab was substantially more effective than rituximab in ...

4. trials.arthritis.org trials.arthritis.org/trials/NCT06087406

A Phase 1b Study of Imvotamab in Moderate to Severe ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with moderate to severe rheumatoid arthritis who have failed ...

5. withpower.com withpower.com/trial/phase-1-rheumatoid-arthritis-8-2023-24e47

Imvotamab for Rheumatoid Arthritis · Info for Participants The available research does not provide specific data on the effectiveness of Imvotamab for Rheumatoid Arthritis. Instead, it focuses on other treatments ...

6. ctv.veeva.com ctv.veeva.com/study/a-phase-1b-study-of-imvotamab-in-moderate-to-severe-rheumatoid-arthritis

A Phase 1b Study of Imvotamab in Moderate to Severe ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with moderate to severe rheumatoid arthritis ...

7. ard.bmj.com ard.bmj.com/content/83/Suppl_1/935.2

POS1062 THERAPEUTIC POTENTIAL OF IMVOTAMAB, A ... 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 ...

8. 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 ...