IMVT-1402 for Rheumatoid Arthritis

Recruiting at 21 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Immunovant Sciences GmbH

Must not be taking: Rituximab, Anti-FcRn

Disqualifiers: Active malignancy, Immunodeficiency, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This Phase 2b, multicenter, double-blind, placebo-controlled, randomized withdrawal study is designed to assess the efficacy and safety of IMVT-1402 in adult participants with active, difficult-to-treat, anti-citrullinated protein autoantibody (ACPA) positive rheumatoid arthritis (RA). The primary objective is to evaluate the effects of IMVT-1402 compared to placebo, as measured by the American College of Rheumatology 20% (ACR20) response.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, it mentions that certain treatments, like non-immunosuppressive Fc-based proteins and anti-FcRn treatments, should not have been used recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug IMVT-1402 for treating rheumatoid arthritis?

The effectiveness of treatments for rheumatoid arthritis has improved with strategies like 'treat-to-target' (T2T), which focuses on achieving remission (no active disease). Advances in therapies, including monoclonal antibodies that target specific inflammatory processes, have shown promise in managing rheumatoid arthritis, suggesting potential for new treatments like IMVT-1402. ^{1 2 3 4 5}

What is the safety profile of Iguratimod for treating rheumatoid arthritis and other conditions?

Iguratimod has been shown to have few adverse events and a safety profile similar to other treatments like methotrexate and sulfasalazine for rheumatoid arthritis. In studies for spondyloarthritis, some patients experienced mild gastrointestinal discomfort and elevated liver enzymes, but overall, it was considered safe and well-tolerated. ^{6 7 8 9 10}

What makes the drug IMVT-1402 unique for treating rheumatoid arthritis?

IMVT-1402 may be unique in treating rheumatoid arthritis by targeting CD147, a molecule involved in T cell activation, which can limit the proliferation of Th17 cells and reduce inflammation and joint damage. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for adults with active, hard-to-treat rheumatoid arthritis who have not responded well to at least two types of advanced RA medications. Participants must meet specific criteria including a definite RA diagnosis, certain levels of joint tenderness and swelling, elevated C-reactive protein, and positive ACPA.

Inclusion Criteria

I meet other specific requirements listed in the study details.

My blood test shows high levels of IgG and ACPA.

My arthritis severity score is above 4.1.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Open-Label Treatment

All eligible participants receive open-label treatment with IMVT-1402 at a dose of 600 mg subcutaneous once weekly for 16 weeks

16 weeks

Randomized Withdrawal

Participants who meet the ACR20 response criteria are randomized to receive blinded treatment with either IMVT-1402 600 mg, IMVT-1402 300 mg, or placebo subcutaneous once weekly for 12 weeks

12 weeks

Long-Term Extension

Eligible participants who complete Period 2 have the option to receive IMVT-1402 for an additional 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IMVT-1402 (Monoclonal Antibodies)

Trial Overview The study tests IMVT-1402 against a placebo in people with difficult rheumatoid arthritis. It's double-blind (neither doctors nor patients know who gets what), randomized (assigned by chance), and aims to see if IMVT-1402 can improve symptoms better than an inactive substance.

Participant Groups

Group I: IMVT-1402 600 mg/ IMVT-1402 600 mg Experimental Treatment 1 Intervention

Period 1: Open-label IMVT-1402 600 mg SC QW Period 2: Randomized to IMVT-1402 600mg SC QW Period 3: IMVT-1402 600 mg SC QW

Group II: IMVT-1402 600 mg/ IMVT-1402 300 mg Experimental Treatment 1 Intervention

Period 1: Open-label IMVT-1402 600 mg SC QW Period 2: Randomized to IMVT-1402 300mg SC QW Period 3: IMVT-1402 300 mg SC QW

Group III: IMVT-1402/Placebo Placebo Group 2 Interventions

Period 1: Open-label IMVT-1402 600 mg SC QW Period 2: Randomized to placebo SC QW Period 3: IMVT-1402 600 mg SC QW

Who Is Running the Clinical Trial?

Immunovant Sciences GmbH

Lead Sponsor

Trials

12

Recruited

1,400+

Findings from Research

The treat-to-target (T2T) initiative aims to establish benchmarks for effectively managing rheumatoid arthritis (RA) treatment, focusing on achieving remission as a primary goal.

Inpatient rheumatology has successfully implemented quality management projects, such as the outcome benchmarking project (OBRA), which align with T2T guidelines, leading to improved outcomes for RA patients through collaboration among competing clinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treat-to-target (T2T) from the perspective of inpatient rheumatology]. Lakomek, HJ., Krause, A.[2021]

The 'treat-to-target' (T2T) approach in rheumatoid arthritis, which focuses on objective measures of disease activity, has been shown to improve clinical outcomes and make remission a realistic goal.

Recent advancements include new definitions of remission and the use of imaging to guide treatment decisions, highlighting the evolving strategies in managing rheumatoid arthritis effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "Treat to Target" Approach to Rheumatoid Arthritis. Salomon-Escoto, K., Kay, J.[2020]

Despite advances in rheumatoid arthritis (RA) treatment, including new therapies and better diagnostic criteria, most patients still do not achieve remission, highlighting the need for ongoing development of novel therapies.

The review discusses new therapeutic antibodies targeting various cytokines and inflammatory mediators, which are in different stages of clinical development, aiming to enhance treatment options for RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies. Senolt, L.[2020]

Recent advances in rheumatoid arthritis treatment have shifted focus to targeting macrophages, particularly the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha).

Clinical trials using antibodies against TNF-alpha have shown promise, highlighting its role as a key therapeutic target in managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapeutic methods against rheumatoid arthritisp6. Antibodies against TNFalpha significant for the progress]. Bondeson, J.[2012]

A study of 1,001 rheumatoid arthritis patients over 8 years showed significant improvements in disease activity and remission rates, particularly after implementing a treat-to-target (T2T) strategy in 2011.

Patients following the T2T strategy achieved remission more frequently (49.3-73.2%) and faster (median time of 21-37 weeks) compared to those who did not follow this strategy, indicating its effectiveness in managing RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in the activity of rheumatoid arthritis as the consequence of treat-to-target strategy: eight-year data from 2009 to 2016. Xie, W., Li, J., Zhang, X., et al.[2019]

Iguratimod demonstrated significant improvements in various measures of rheumatoid arthritis (RA) symptoms compared to placebo after 24 weeks of treatment in a meta-analysis of four randomized controlled trials involving 1407 patients.

The safety profile of iguratimod was favorable, with few adverse events reported, and its efficacy was comparable to that of other disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) and sulfasalazine (SASP), although further high-quality studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iguratimod for the treatment of rheumatoid arthritis. Li, J., Mao, H., Liang, Y., et al.[2021]

The Rheumatology Common Toxicity Criteria (RCTC) was revised to improve the standardization of assessing and reporting adverse events in rheumatology clinical trials, with a focus on terms like disease flares and drug hypersensitivity.

A moderate consensus (62%) was reached to implement the revised RCTC v.2.0 in trials involving anti-tumor necrosis factor agents, highlighting its potential effectiveness and the need for further validation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0. Woodworth, T., Furst, DE., Alten, R., et al.[2022]

In a study involving 73 participants with active spondyloarthritis (SpA), Iguratimod significantly improved symptoms, with 80% of patients responding positively compared to 44% in the placebo group after 24 weeks.

The treatment was well-tolerated, with similar rates of gastrointestinal discomfort and liver enzyme elevation between the Iguratimod and placebo groups, indicating good safety and tolerance for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised, Double-Blind, Placebo-Controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis. Li, Y., Li, K., Zhao, Z., et al.[2021]

Methotrexate (MTX) used as the initial second-line treatment for rheumatoid arthritis (RA) showed a higher remission rate (28.6%) compared to patients who received it after other DMARDs (9.1%), indicating its potential effectiveness when used early.

The toxicity profiles and reasons for discontinuation of MTX were similar between the two groups, suggesting that starting MTX earlier does not increase the risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients. Bologna, C., Jorgensen, C., Sany, J.[2017]

Anakinra, administered at 100 mg/day for up to three years, demonstrated a safety profile similar to placebo in a diverse group of 1346 rheumatoid arthritis patients, with no significant trends in laboratory data or serious adverse events related to the drug.

While there was a higher rate of serious infections in patients treated with anakinra compared to controls, this rate was significantly lower in patients not on corticosteroids, indicating that the safety of anakinra may be influenced by concurrent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Fleischmann, RM., Tesser, J., Schiff, MH., et al.[2018]

CD147 is found to be involved in regulating Th17 cell responses in rheumatoid arthritis (RA), with increased expression on CD4+ T cells linked to IL-17 production in both RA patients and healthy controls.

Treatment with an anti-CD147 monoclonal antibody significantly inhibited Th17 responses and reduced the severity of arthritis in a collagen-induced arthritis model, suggesting it could be a promising new therapeutic option for RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD147 Expressed on Memory CD4+ T Cells Limits Th17 Responses in Patients With Rheumatoid Arthritis. Miao, J., Zhang, K., Zheng, Z., et al.[2021]

CD147 is significantly upregulated in memory T cells from rheumatoid arthritis (RA) patients, indicating its potential role in the abnormal activation of these cells in the disease.

The anti-CD147 monoclonal antibody 5A12 effectively inhibits the activation and proliferation of memory T cells, suggesting it could be a promising therapeutic target for treating RA and other T-cell-mediated autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical epitope in CD147 facilitates memory CD4+ T-cell hyper-activation in rheumatoid arthritis. Guo, N., Ye, S., Zhang, K., et al.[2021]

Neutrophils enhance the production of matrix metalloproteinases (MMP-2 and MMP-9) in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients through CD147, indicating a mechanism that contributes to inflammation and tissue destruction in RA.

The invasive potential of RA FLS is increased by neutrophils, and this effect can be significantly inhibited by an antagonist peptide against CD147 (AP-9), suggesting a potential therapeutic target for reducing joint damage in RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neutrophil enhanced matrix metalloproteinase production and invasion of synoviocytes of RA via CD147]. Liang, XH., Zhu, P., Yang, Y., et al.[2017]

CD147 is linked to increased levels of VEGF and HIF-1α, which promote angiogenesis in rheumatoid arthritis (RA), suggesting that targeting CD147 could help reduce inflammation and blood vessel growth in this disease.

In experiments with RA fibroblast-like synoviocytes and a mouse model, inhibiting CD147 led to a greater reduction in VEGF and HIF-1α production compared to the standard treatment infliximab, indicating that CD147 suppression may be a more effective therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis. Wang, CH., Yao, H., Chen, LN., et al.[2017]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Treat-to-target (T2T) from the perspective of inpatient rheumatology]. [2021]

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

The "Treat to Target" Approach to Rheumatoid Arthritis. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies. [2020]

4. Sweden pubmed.ncbi.nlm.nih.gov

[New therapeutic methods against rheumatoid arthritisp6. Antibodies against TNFalpha significant for the progress]. [2012]

5. Italy pubmed.ncbi.nlm.nih.gov

Trends in the activity of rheumatoid arthritis as the consequence of treat-to-target strategy: eight-year data from 2009 to 2016. [2019]

6. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iguratimod for the treatment of rheumatoid arthritis. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Randomised, Double-Blind, Placebo-Controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis. [2021]

9. Italy pubmed.ncbi.nlm.nih.gov

Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Safety of extended treatment with anakinra in patients with rheumatoid arthritis. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

CD147 Expressed on Memory CD4+ T Cells Limits Th17 Responses in Patients With Rheumatoid Arthritis. [2021]

12. China pubmed.ncbi.nlm.nih.gov

A critical epitope in CD147 facilitates memory CD4+ T-cell hyper-activation in rheumatoid arthritis. [2021]

13. Germany pubmed.ncbi.nlm.nih.gov

CD147 participates in the activation function of circulating angiogenic T cells in patients with rheumatoid arthritis. [2020]

14. China pubmed.ncbi.nlm.nih.gov

[Neutrophil enhanced matrix metalloproteinase production and invasion of synoviocytes of RA via CD147]. [2017]

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

CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis. [2017]