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

NCT05198310 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: KPL-404-C2112022-000169-42
• Study Type: interventional
• Target: 145
• Locations: 7 countries
• Sites: 42

Brief Summary

Phase 2 study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of KPL-404 in subjects with moderate to severe Rheumatoid Arthritis.

Conditions

Arthritis, Rheumatoid

Keywords

inadequate responders; moderate to severe; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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.

  From first dose of study drug to 24 weeks

• 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

  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.

  Baseline, Week 12

Secondary Outcomes (7)

• 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)

• Cohort 3 and 4: AUCtau

  Days 1 (Dose 1) and 57 (Dose 4 or 8)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12

  Baseline, Week 12

Study Arms (9)

Cohort 1 KPL-404 2 mg/kg Every 2 Weeks (q2wk)

EXPERIMENTAL

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

Drug: KPL-404

Cohort 1 Placebo

PLACEBO COMPARATOR

Placebo SC q2wk for 12 weeks

Drug: Placebo

Cohort 2 KPL-404 5 mg/kg q2wk

EXPERIMENTAL

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

Drug: KPL-404

Cohort 2 Placebo

PLACEBO COMPARATOR

Placebo SC q2wk for 12 weeks

Drug: Placebo

Cohort 3 KPL-404 5 mg/kg qwk

EXPERIMENTAL

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

Drug: KPL-404

Cohort 3 KPL-404 5 mg/kg q2wk

EXPERIMENTAL

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

Drug: KPL-404; Drug: Placebo

Cohort 3 Placebo

PLACEBO COMPARATOR

Placebo SC qwk for 12 weeks

Drug: Placebo

Cohort 4 KPL-404 400 mg q4wk

EXPERIMENTAL

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.

Drug: KPL-404

Cohort 4 Placebo

PLACEBO COMPARATOR

Placebo SC q4wk for 12 weeks

Drug: Placebo

Interventions

KPL-404 DRUG

Humanized monoclonal antibody

Also known as: abiprubart

Cohort 1 KPL-404 2 mg/kg Every 2 Weeks (q2wk); Cohort 2 KPL-404 5 mg/kg q2wk; Cohort 3 KPL-404 5 mg/kg q2wk; Cohort 3 KPL-404 5 mg/kg qwk; Cohort 4 KPL-404 400 mg q4wk

Placebo DRUG

Matching placebo

Cohort 1 Placebo; Cohort 2 Placebo; Cohort 3 KPL-404 5 mg/kg q2wk; Cohort 3 Placebo; Cohort 4 Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Treated with a biological disease-modifying anti-rheumatic drug (bDMARDs) AND/OR Janus kinase inhibitor (JAKi) therapy for RA for ≥ 3 months and had inadequate response or had to discontinue bDMARD AND/OR JAKi therapy due to intolerance or toxicity, regardless of treatment duration.
• Currently receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks before the first dose of investigational product.
• The following csDMARDs are allowed: oral or parenteral methotrexate (\[MTX\]; 7.5 to 25 mg/week), sulfasalazine (≤ 3000 mg/day), hydroxychloroquine (≤ 400 mg/day), chloroquine (≤ 250 mg/day), and leflunomide (≤ 20 mg/day).
• A combination of up to 2 background csDMARDs is allowed, except the combination of MTX and leflunomide.
• Meets all of the following disease activity criteria:
• Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;
• Level of high-sensitivity C-reactive protein ≥ 3 mg/L (by central laboratory);
• Documented seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) (\>ULN) at screening or by prior laboratory evaluation.
• Has completed a locally approved authorized COVID-19 vaccine regimen according to local guidance at least 3 weeks before the first dose of the Investigational Product.
• Must have discontinued all bDMARDs or JAKi prior to the first dose of investigational product. The washout period for bDMARDs or JAKi prior to the first dose of investigational product is specified below. For bDMARDs or JAKi not listed below washout should be at least 5 times the mean elimination half-life of a drug:
• ≥ 4 weeks for etanercept;
• ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab;
• ≥ 1 year for rituximab;

You may not qualify if:

• Prior exposure to any other anti-CD40/CD40L agent.
• Inadequate response to 5 or more classes of advanced targeted therapies (bDMARD or tsDMARD; e.g., TNF inhibitors, IL-6 receptor inhibitors, T-cell costimulatory inhibitors, anti-CD-20 antibodies, JAK inhibitors). This does not include prior discontinuation due to drug intolerance.
• Injectable corticosteroids (including intra-articular) or treatment with \> 10 mg/day dose oral prednisone or equivalent within 8 weeks prior to randomization.
• History of any arthritis with onset prior to age 16 years or current diagnosis of inflammatory joint disease other than RA (Current diagnosis of secondary Sjogren's syndrome is permitted).
• History of thromboembolic event or a significant risk of future thromboembolic events
• Clinically significant active infection including signs/symptoms suggestive of infection, any significant recurrent or chronic infection, or subjects at a high risk of infection
• History of cancer within the last 5 years from screening, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
• History of any of the following cardiovascular conditions:
• Moderate to severe congestive heart failure (New York Heart Association class III or IV);
• Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;
• Uncontrolled hypertension as defined by a confirmed systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.
• Clinically relevant or significant electrocardiogram (ECG) abnormalities, including ECG with QT interval corrected for heart rate (QTc) \> 500 msec.

Sponsors & Collaborators

• Kiniksa Pharmaceuticals, Ltd.: lead

Study Sites (42)

Carewell Arthritis Center

Apple Valley, California, 92307, United States

Location

Medvin Clinical Research

Covina, California, 91722, United States

Location

Inland Rheumatology Clinical Trials

Upland, California, 91786, United States

Location

Medvin Clinical Research

Whittier, California, 90602, United States

Location

International Medical Research

Daytona Beach, Florida, 32117, United States

Location

Sweet Hope Research Specialty, Inc.

Hialeah, Florida, 33016, United States

Location

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, 33014, United States

Location

Millennium Research

Ormond Beach, Florida, 32174, United States

Location

West Broward Rheumatology Associates, Inc.

Tamarac, Florida, 33321, United States

Location

Paramount Medical Research & Consulting, LLC

Middleburg Heights, Ohio, 44130, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Saint Francis Hospital- Memphis

Memphis, Tennessee, 38119, United States

Location

Arthritis and Rheumatology Research Institute

Allen, Texas, 75013, United States

Location

Trinity Universal Research Assoc

Carrollton, Texas, 75007, United States

Location

Arthritis & Osteoporosis Center of Coastal Bend

Corpus Christi, Texas, 78404, United States

Location

Southwest Rheumatology Research LLC

Mesquite, Texas, 75150, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

Rheumatology Clinic of Houston

Tomball, Texas, 77377, United States

Location

Rheumatology and Pulmonary Clinic

Beckley, West Virginia, 25801, United States

Location

Medical center "Artmed" LTD

Plovdiv, 4002, Bulgaria

Location

Vesalion s.r.o.

Ostrava, 702 00, Czechia

Location

Revmatologicky Utsav

Prague, 128 50, Czechia

Location

Medical Plus S.R.O.

Uherské Hradiště, 686 01, Czechia

Location

Aleksandre Aladashvili Clinic LLC

Tbilisi, 0102, Georgia

Location

LTD Israel-Georgian Medical Research Clinic Helsicore

Tbilisi, 0112, Georgia

Location

JSC Evex Hospitals

Tbilisi, 0159, Georgia

Location

LTD Georgian-Dutch Hospital

Tbilisi, 0172, Georgia

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, 6725, Hungary

Location

Qualiclinic Ltd (Qualiclinic Inc)

Budapest, 1036-H, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, 1062, Hungary

Location

Porcika Klinika

Hódmezővásárhely, 6800, Hungary

Location

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

Vita Verum Medical Egeszsegugy

Székesfehérvár, 8000, Hungary

Location

Centrum Kliniczno-Badawcze

Elblag, 82-300, Poland

Location

Silmedic sp. z o.o.

Katowice, 40-282, Poland

Location

Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj

Poznan, 61-397, Poland

Location

RCMed Oddzial Sochaczew

Sochaczew, 96-500, Poland

Location

Centrum Medyczne Reuma Park

Warsaw, Poland

Location

Clinresco Centres (Pty) Ltd

Kempton Park, Gauteng, 1619, South Africa

Location

Jacaranda Hospital

Pretoria, Gauteng, 0002, South Africa

Location

Umhlanga Hospital Medical Center

Umhlanga, KwaZulu-Natal, 4319, South Africa

Location

Panorama Medical Centre

Cape Town, Western Cape, 7500, South Africa

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Clinical Operations Study Director
• Organization: Kiniksa Pharmaceuticals, Ltd.

studyinfo@kiniksa.com

1-781-431-9100

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2022
• First Posted: January 20, 2022
• Study Start: December 14, 2021
• Primary Completion: February 8, 2024
• Study Completion: May 6, 2024
• Last Updated: July 22, 2025
• Results First Posted: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (4); HU (6); BU (1); CZ (3); GE (4); US (19); PL (5)