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KPL-404

Phase 2

Arthritis, Rheumatoid | Small molecule | Immunology |Kiniksa Pharmaceuticals International, plc|Last Updated: Jul 22, 2025

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment145

FDA Designations

No designations recorded

Clinical trial landscape

KPL-404 · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT05198310Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase InhibitorArthritis, Rheumatoid
COMPLETED145 Analytics
PHASE2COMPLETED
Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor
Arthritis, RheumatoidUnlock trial analytics

Study Endpoints

Primary Endpoints

Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
From first dose of study drug to 24 weeks

Adverse event (AE): any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. Serious AE (SAE): AE that: results in death; is immediately life-threatening; requires in-patient hospitalization/prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital abnormality/birth defect; is an important medical event. TEAEs: AEs not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug during treatment period. AE severity: mild (Grade \[Gr\] 1); moderate (Gr 2); severe (Gr 3); potentially life threatening (Gr 4); death (Gr 5). AEs of special interest: thrombosis, serious infection, serious and non-serious bacterial infections, eye disorders, and anaphylaxis/hypersensitivity reactions.

Cohorts 1 and 2: Maximum Serum Concentration (Cmax)
Days 1 (Dose 1) and 57 (Dose 4)
Cohorts 1 and 2: Area Under the Serum Concentration-time Curve From Time of Administration to the End of the Dosing Interval, (AUCtau)
Days 1 (Dose 1) and 57 (Dose 4)
Cohort 3 and 4: Change From Baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12
Baseline, Week 12

DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). DAS28-CRP is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score \< 2.6, low disease activity = score \< 3.2). A negative value in change from BL indicates an improvement.

TEAEs following IV dosing
Up to 65 days post dose

After single ascending IV doses, number of subjects with treatment-emergent adverse events (TEAEs) in the KPL-404 dose-level cohorts compared with the (pooled) IV placebo group

TEAEs following SC dosing
Up to 65 days post dose

After single ascending SC doses, number of subjects with treatment-emergent adverse events (TEAEs) in the KPL-404 dose-level cohorts compared with the (pooled) SC placebo group

Secondary Endpoints

Cohorts 1 and 2: Change From Baseline in DAS28-CRP at Week 12
Baseline, Week 12
Cohorts 3 and 4: Number of Participants With TEAEs
From first dose of study drug to 24 weeks
Cohort 3 and 4: Cmax
Days 1 (Dose 1) and 57 (Dose 4 or 8)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort 1 KPL-404 2 mg/kg Every 2 Weeks (q2wk)EXPERIMENTALKPL-404 2 mg/kg subcutaneous (SC) q2wk for 12 weeks
Cohort 1 PlaceboPLACEBO_COMPARATORPlacebo SC q2wk for 12 weeks
Cohort 2 KPL-404 5 mg/kg q2wkEXPERIMENTALKPL-404 5 mg/kg SC q2wk for 12 weeks
Cohort 2 PlaceboPLACEBO_COMPARATORPlacebo SC q2wk for 12 weeks
Cohort 3 KPL-404 5 mg/kg qwkEXPERIMENTALKPL-404 5mg/kg SC once weekly (qwk) for 12 weeks
Cohort 3 KPL-404 5 mg/kg q2wkEXPERIMENTALKPL-404 5mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
Cohort 3 PlaceboPLACEBO_COMPARATORPlacebo SC qwk for 12 weeks
Cohort 4 KPL-404 400 mg q4wkEXPERIMENTALKPL-404 SC every 4 weeks (q4wk) for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at Weeks 4 and 8.
Cohort 4 PlaceboPLACEBO_COMPARATORPlacebo SC q4wk for 12 weeks
KPL-404 (IV Administration)EXPERIMENTAL -
KPL-404 (SC Administration)EXPERIMENTAL -

Interventions

NameTypeDescription
KPL-404DRUGHumanized monoclonal antibody
PlaceboDRUGMatching placebo
Matching PlaceboOTHERPlacebo
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites42

Inclusion Criteria: * Body weight ≥ 40 to ≤ 140 kg for all cohorts. * Diagnosis of RA for ≥ 3 months fulfilling the 2010 American College of Rheumatology (ACR)/European Union League Against Rheumatism (EULAR) classification criteria for RA and that is categorized as ACR RA functional Class 1-3. * T...

Countries:United StatesBulgariaCzechiaGeorgiaHungaryPolandSouth AfricaAustralia
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Frequently asked questions about KPL-404

What is KPL-404 used for in rheumatoid arthritis?

KPL-404 is an investigational small molecule being studied for rheumatoid arthritis in patients with an inadequate response or intolerance to at least one biologic disease-modifying anti-rheumatic drug or a Janus kinase inhibitor. It is also being evaluated in healthy volunteers to assess safety, tolerability, pharmacokinetics, and pharmacodynamics.

Who makes KPL-404?

KPL-404 is being developed by Kiniksa Pharmaceuticals International, plc, a biopharmaceutical company traded on the stock exchange under the ticker KNSA. The company is conducting clinical trials to evaluate the drug's safety and efficacy in rheumatoid arthritis and healthy volunteers.

What phase is KPL-404 in?

KPL-404 is in Phase 2 clinical development for rheumatoid arthritis. A Phase 1 study in healthy volunteers has been completed. The drug is investigational and has not been approved by regulatory authorities, as it is still undergoing clinical evaluation.

What clinical trials is KPL-404 in?

KPL-404 has been studied in two completed clinical trials. NCT04497662 was a Phase 1 single ascending dose study in 52 healthy volunteers in the United States and Australia. NCT05198310 was a Phase 2 study in 145 participants with rheumatoid arthritis across multiple countries including the United States, Bulgaria, Czechia, Georgia, Hungary, Poland, and South Africa.

Is KPL-404 the same as any other drug?

KPL-404 is not known to be the same as any other drug. It is a distinct investigational small molecule developed by Kiniksa Pharmaceuticals. No alternative names have been reported for this compound in the clinical trial information available.