What side effects are associated with this type of intervention?

Common treatments for Rheumatoid Arthritis that modulate the immune response include methotrexate, TNF-alpha inhibitors, and glucocorticoids. Methotrexate can cause liver toxicity, bone marrow suppression, and gastrointestinal issues. TNF-alpha inhibitors, such as infliximab and adalimumab, may lead to increased risk of infections, injection site reactions, and potential lung toxicity. Glucocorticoids can result in weight gain, osteoporosis, hypertension, and increased susceptibility to infections. These side effects necessitate careful monitoring and individualized treatment plans.

What prior FDA approvals exist?

Several biologic agents have been approved by the FDA for the treatment of Rheumatoid Arthritis, focusing on modulating the immune response. These include tumor necrosis factor (TNF) inhibitors such as adalimumab, infliximab, and etanercept, which block the activity of TNF-alpha, a cytokine involved in systemic inflammation. Another class includes B cell depleting agents like rituximab, which targets CD20 on B cells. Additionally, abatacept, which modulates T-cell activation, has been approved for patients with an inadequate response to other treatments. These drugs have shown varying degrees of effectiveness and safety in clinical trials and postmarketing surveillance.

What other types of research exist?

Promising alternatives to KPL-404 for Rheumatoid Arthritis patients include CRAC inhibitors such as YM-58483, which have shown potential in altering proinflammatory cytokine production and providing global immunosuppression. Other options include biologic agents like TNF inhibitors, IL-17 inhibitors, and JAK inhibitors, which have demonstrated efficacy in RA treatment.

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Monoclonal Antibodies

KPL-404 for Rheumatoid Arthritis

Phase 2

Waitlist Available

Research Sponsored by Kiniksa Pharmaceuticals, Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must meet specific disease activity criteria including joint counts, C-reactive protein levels, and seropositivity for Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA)

Diagnosis of Rheumatoid Arthritis (RA) for at least 3 months meeting the 2010 ACR/EULAR classification criteria for RA and categorized as ACR RA functional Class 1-3

Must not have

History of specific cardiovascular conditions including congestive heart failure, recent cerebrovascular accident, uncontrolled hypertension, and significant ECG abnormalities

Prior exposure to any other anti-CD40/CD40L agent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

This trial tests KPL-404, a new medication for moderate to severe Rheumatoid Arthritis. It focuses on patients who haven't responded well to other treatments. The study will evaluate how safe and effective KPL-404 is and how it works in the body.

Who is the study for?

Adults with moderate to severe Rheumatoid Arthritis who haven't responded well or are intolerant to at least one biologic DMARD or a JAK inhibitor. They should be on stable csDMARD therapy, have active disease indicated by joint counts and lab tests, and must have completed their COVID-19 vaccination. Excluded are those with recent steroid injections, prior anti-CD40/CD40L treatment, early arthritis onset before age 16, high thromboembolic risk, certain heart conditions, uncontrolled hypertension, significant ECG abnormalities or a history of cancer (except some skin cancers).

What is being tested?

The trial is testing KPL-404's safety and effectiveness in people with Rheumatoid Arthritis compared to a placebo. It's looking at how the body processes the drug (pharmacokinetics), how it affects the body (pharmacodynamics), and if it improves symptoms.

What are the potential side effects?

Potential side effects for KPL-404 aren't specified but may include typical reactions seen in immune-modulating therapies such as injection site reactions, increased infection risk due to immune system suppression, gastrointestinal issues like nausea or diarrhea.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My arthritis shows active disease with specific blood test results.

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I have been diagnosed with Rheumatoid Arthritis for at least 3 months and can perform daily activities with little to some difficulty.

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I have rheumatoid arthritis and treatments with bDMARDs or JAKi for over 3 months didn't work or caused side effects.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of serious heart or blood pressure problems.

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I have never been treated with anti-CD40/CD40L drugs.

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I was diagnosed with arthritis before I turned 16 or have an inflammatory joint disease that is not RA.

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I have had blood clots or am at high risk for them.

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I haven't had any cancer except for certain types in the last 5 years.

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I currently have a serious infection or am at high risk for one.

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My condition didn't improve after trying 5 different targeted therapies.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Trial Design

9Treatment groups

Experimental Treatment

Placebo Group

Group I: Cohort 4 KPL-404Experimental Treatment1 Intervention

KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at weeks 4 and 8.

Group II: Cohort 3 KPL-404 and PlaceboExperimental Treatment2 Interventions

KPL-404 5mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks

Group III: Cohort 3 KPL-404Experimental Treatment1 Intervention

KPL-404 5mg/kg SC qwk for 12 weeks

Group IV: Cohort 2 KPL-404Experimental Treatment1 Intervention

KPL-404 5mg/kg SC q2wk for 12 weeks

Group V: Cohort 1 KPL-404Experimental Treatment1 Intervention

KPL-404 2mg/kg Subcutaneous (SC) q2wk for 12 weeks

Group VI: Cohort 2 PlaceboPlacebo Group1 Intervention

Placebo for KPL-404 SC q2wk for 12 weeks

Group VII: Cohort 3 PlaceboPlacebo Group1 Intervention

Placebo for KPL-404 SC qwk for 12 weeks

Group VIII: Cohort 4 PlaceboPlacebo Group1 Intervention

Placebo for KPL-404 SC q4wk for 12 weeks

Group IX: Cohort 1 PlaceboPlacebo Group1 Intervention

Placebo for KPL-404 SC q2wk for 12 weeks

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

KPL-404

2021

Completed Phase 2

~200

Placebo

1995

Completed Phase 3

~2670

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Rheumatoid Arthritis (RA) primarily focus on modulating the immune response to reduce inflammation and prevent joint damage. Disease-Modifying Antirheumatic Drugs (DMARDs) like methotrexate inhibit the proliferation of immune cells. Biologic agents, such as TNF-alpha inhibitors (e.g., infliximab, adalimumab), block specific cytokines involved in the inflammatory process. Janus kinase (JAK) inhibitors interfere with intracellular signaling pathways that contribute to inflammation. These mechanisms are vital for RA patients as they help control symptoms, slow disease progression, and improve overall quality of life.

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