KPL-404 for Rheumatoid Arthritis

No longer recruiting at 68 trial locations

Overseen By Clinical Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kiniksa Pharmaceuticals, Ltd.

Must be taking: CsDMARDs

Must not be taking: Injectable corticosteroids

Disqualifiers: Cancer, Cardiovascular conditions, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called KPL-404 for people with moderate to severe Rheumatoid Arthritis (RA), focusing on its safety and effectiveness. Participants will receive either KPL-404 or a placebo for comparison. This study suits individuals diagnosed with RA for at least three months who have not found other treatments effective. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in RA treatment.

Will I have to stop taking my current medications?

You will need to stop taking any biological disease-modifying anti-rheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) before starting the trial. The required time without these medications (washout period) varies: 4 weeks for etanercept, 8 weeks for several others, 1 year for rituximab, and 2 weeks for JAKi. However, you can continue taking certain conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) if they are stable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KPL-404 was well tolerated in earlier studies. Participants experienced no major safety issues. Lab tests and vital signs, such as heart rate and blood pressure, revealed no significant problems. This suggests that KPL-404 is generally safe for people. However, as an experimental treatment, ongoing monitoring in trials remains necessary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about KPL-404 for rheumatoid arthritis because it offers a unique approach compared to existing treatments like methotrexate or biologics such as TNF inhibitors. Unlike these treatments, which generally target broad immune responses, KPL-404 specifically blocks the CD40-CD154 pathway, a key player in the immune response that contributes to inflammation and joint damage in rheumatoid arthritis. This targeted mechanism could potentially lead to fewer side effects and more effective disease management. Additionally, KPL-404's varied dosing regimens, including subcutaneous administration, provide flexibility that could enhance patient compliance and convenience.

What evidence suggests that KPL-404 might be an effective treatment for Rheumatoid Arthritis?

Research shows that KPL-404, also known as abiprubart, may help treat rheumatoid arthritis. In this trial, participants will receive different dosages of KPL-404 or a placebo. Studies with patients who didn't respond well to other treatments have shown that KPL-404 significantly reduced symptoms after 12 weeks compared to a placebo. Patients experienced fewer symptoms and felt better. The treatment blocks a specific interaction in the immune system that attacks the joints, aiming to reduce inflammation and joint damage. Overall, findings suggest KPL-404 could effectively manage moderate to severe rheumatoid arthritis. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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).

Inclusion Criteria

My arthritis shows active disease with specific blood test results.

I completed my COVID-19 vaccination at least 3 weeks ago.

I have been on stable rheumatoid arthritis medication for at least 4 weeks.

Exclusion Criteria

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

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

I haven't taken high-dose steroids or injections in the last 8 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive KPL-404 or placebo for 12 weeks with varying dosing schedules

12 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KPL-404

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort 4 KPL-404 400 mg q4wk Experimental Treatment 1 Intervention

KPL-404 SC every 4 weeks (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 5 mg/kg qwk Experimental Treatment 1 Intervention

KPL-404 5mg/kg SC once weekly (qwk) for 12 weeks

Group III: Cohort 3 KPL-404 5 mg/kg q2wk Experimental Treatment 2 Interventions

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

Group IV: Cohort 2 KPL-404 5 mg/kg q2wk Experimental Treatment 1 Intervention

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

Group V: Cohort 1 KPL-404 2 mg/kg Every 2 Weeks (q2wk) Experimental Treatment 1 Intervention

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

Group VI: Cohort 2 Placebo Placebo Group 1 Intervention

Placebo SC q2wk for 12 weeks

Group VII: Cohort 3 Placebo Placebo Group 1 Intervention

Placebo SC qwk for 12 weeks

Group VIII: Cohort 4 Placebo Placebo Group 1 Intervention

Placebo SC q4wk for 12 weeks

Group IX: Cohort 1 Placebo Placebo Group 1 Intervention

Placebo SC q2wk for 12 weeks

Who Is Running the Clinical Trial?

Kiniksa Pharmaceuticals, Ltd.

Lead Sponsor

Trials

9

Recruited

1,400+

Citations

1. ard.bmj.com ard.bmj.com/content/83/Suppl_1/81

A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED 12- ... Abiprubart (KPL-404) is a humanized monoclonal IgG4 antibody with a stabilized/functionally-silent Fc region that binds to CD40 and inhibits the CD40/CD154 ...

2. kiniksa.com kiniksa.com/2024-eular-ph2-ra-oral-presentation-final-07jun2024.pdf

efficacy, safety, and pharmacokinetics of In refractory RA patients, abiprubart treatment resulted in a statistically significant reduction in. DAS28-CRP at Week 12 compared to placebo in the 5mg/kg SC ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05198310

NCT05198310 | Study to Assess the Safety, ... The objectives of the study are to evaluate safety, efficacy, and PD of KPL-404 compared with placebo across the estimated therapeutic range and to characterize ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022356524171236

First-in-Human Phase 1 Randomized Trial with the Anti ... Blockade of the cluster of differentiation 40 (CD40)–CD40L interaction has potential for treating autoimmune diseases and preventing graft rejection.

5. acrabstracts.org acrabstracts.org/abstract/efficacy-safety-pharmacokinetics-of-anti-cd40-antibody-abiprubart-in-patients-with-rheumatoid-arthritis-a-phase-2-randomized-placebo-controlled-12-week-treatment-proof-of-concept-study/

Efficacy, Safety, Pharmacokinetics of Anti-CD40 Antibody ... Abiprubart was well-tolerated in pts with b/tsDMARD-refractory RA, and reductions in DAS28-CRP at Wk 12 for all abiprubart groups were greater than PBO.

6. kiniksa.com kiniksa.com/2021-acr-samant-kpl-404-ph1.pdf

2021-acr-samant-kpl-404-ph1.pdf KPL-404 was well tolerated with no safety signals based on the evaluation of AEs, clinical laboratory findings, and vital signs measurements in participants ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35078863/

Preclinical Immunopharmacologic Assessment of KPL-404, ... These data support clinical development of KPL-404 in autoimmune diseases. SIGNIFICANCE STATEMENT: We aimed to develop a potent and efficacious CD40 antagonist.