Study to Assess the Safety, Pharmacokinetics, and Efficac... | NCT05198310 | Trialant
NCT05198310
Sponsor
Kiniksa Pharmaceuticals, Ltd.
Status
Completed
Last Update Posted
Jul 22, 2025Actual
Enrollment
145Actual
Phase
Phase 2
Conditions
Arthritis, Rheumatoid
Interventions
KPL-404
Placebo
Countries
United States
Bulgaria
Czechia
Georgia
Hungary
Poland
South Africa
Protocol Section
Identification Module
NCT ID
NCT05198310
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
KPL-404-C211
Secondary IDs
ID
Type
Description
Link
2022-000169-42
EudraCT Number
Brief Title
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
Official Title
A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Subjects With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 14, 2021Actual
Primary Completion Date
Feb 8, 2024Actual
Completion Date
May 6, 2024Actual
First Submitted Date
Jan 3, 2022
First Submission Date that Met QC Criteria
Jan 3, 2022
First Posted Date
Jan 20, 2022Actual
Results Waived
Not provided
Results First Submitted Date
Jul 2, 2025
Results First Submitted that Met QC Criteria
Jul 2, 2025
Results First Posted Date
Jul 22, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 31, 2025
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Jun 10, 2024Actual
Last Update Submitted Date
Jul 2, 2025
Last Update Posted Date
Jul 22, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Kiniksa Pharmaceuticals, Ltd.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
This is a 28-week (up to 4-week screening period, 12-week treatment period, and 12-week safety follow-up period), multicenter, randomized, double-blind, placebo-controlled, multiple dose, proof-of-concept study with PK lead-in designed to assess the safety, PK, efficacy and PD of KPL-404 in subjects with moderate to severe, active Rheumatoid Arthritis (RA) who have an inadequate response to or are intolerant to a Janus kinase inhibitor (JAKi) AND/OR at least one biologic disease-modifying anti-rheumatic drug (bDMARD). 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 PK across varying dose levels of KPL-404.
Conditions Module
Conditions
Arthritis, Rheumatoid
Keywords
inadequate responders
moderate to severe
Rheumatoid Arthritis
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
145Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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
Interventions
Name
Type
Description
Arm Group Labels
Other Names
KPL-404
Drug
Humanized monoclonal antibody
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
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
Measure
Description
Time Frame
Cohorts 1 and 2: Change From Baseline in 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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
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;
≥ 2 weeks for JAKi (either investigational or commercially available treatment).
Voluntarily sign and date an informed consent form approved by independent ethics committee/Institutional Review Board (IRB)
Exclusion Criteria:
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);
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
Cohort 3 KPL-404 5 mg/kg qwk
Cohort 4 KPL-404 400 mg q4wk
abiprubart
Placebo
Drug
Matching placebo
Cohort 1 Placebo
Cohort 2 Placebo
Cohort 3 KPL-404 5 mg/kg q2wk
Cohort 3 Placebo
Cohort 4 Placebo
Baseline, Week 12
Cohorts 3 and 4: Number of Participants With 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
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
An ACR20 response is defined as at least a 20% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 20% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
Baseline, Week 12
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
An ACR50 response is defined as at least a 50% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 50% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
Baseline, Week 12
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
An ACR70 response is defined as at least a 70% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 70% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
Baseline, Week 12
Covina
California
91722
United States
Inland Rheumatology Clinical Trials
Upland
California
91786
United States
Medvin Clinical Research
Whittier
California
90602
United States
International Medical Research
Daytona Beach
Florida
32117
United States
Sweet Hope Research Specialty, Inc.
Hialeah
Florida
33016
United States
San Marcus Research Clinic, Inc.
Miami Lakes
Florida
33014
United States
Millennium Research
Ormond Beach
Florida
32174
United States
West Broward Rheumatology Associates, Inc.
Tamarac
Florida
33321
United States
Paramount Medical Research & Consulting, LLC
Middleburg Heights
Ohio
44130
United States
Altoona Center for Clinical Research
Duncansville
Pennsylvania
16635
United States
Saint Francis Hospital- Memphis
Memphis
Tennessee
38119
United States
Arthritis and Rheumatology Research Institute
Allen
Texas
75013
United States
Trinity Universal Research Assoc
Carrollton
Texas
75007
United States
Arthritis & Osteoporosis Center of Coastal Bend
Corpus Christi
Texas
78404
United States
Southwest Rheumatology Research LLC
Mesquite
Texas
75150
United States
DM Clinical Research
Tomball
Texas
77375
United States
Rheumatology Clinic of Houston
Tomball
Texas
77377
United States
Rheumatology and Pulmonary Clinic
Beckley
West Virginia
25801
United States
Medical center "Artmed" LTD
Plovdiv
4002
Bulgaria
Vesalion s.r.o.
Ostrava
702 00
Czechia
Revmatologicky Utsav
Prague
128 50
Czechia
Medical Plus S.R.O.
Uherské Hradiště
686 01
Czechia
Aleksandre Aladashvili Clinic LLC
Tbilisi
0102
Georgia
LTD Israel-Georgian Medical Research Clinic Helsicore
Tbilisi
0112
Georgia
JSC Evex Hospitals
Tbilisi
0159
Georgia
LTD Georgian-Dutch Hospital
Tbilisi
0172
Georgia
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged
Csongrád megye
6725
Hungary
Qualiclinic Ltd (Qualiclinic Inc)
Budapest
1036-H
Hungary
Magyar Honvedseg Egeszsegugyi Kozpont
Budapest
1062
Hungary
Porcika Klinika
Hódmezővásárhely
6800
Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
Nyíregyháza
4400
Hungary
Vita Verum Medical Egeszsegugy
Székesfehérvár
8000
Hungary
Centrum Kliniczno-Badawcze
Elblag
82-300
Poland
Silmedic sp. z o.o.
Katowice
40-282
Poland
Prywatna Praktyka Lekarska Prof. UM dr hab.med. Pawel Hrycaj
Poznan
61-397
Poland
RCMed Oddzial Sochaczew
Sochaczew
96-500
Poland
Centrum Medyczne Reuma Park
Warsaw
Poland
Clinresco Centres (Pty) Ltd
Kempton Park
Gauteng
1619
South Africa
Jacaranda Hospital
Pretoria
Gauteng
0002
South Africa
Umhlanga Hospital Medical Center
Umhlanga
KwaZulu-Natal
4319
South Africa
Panorama Medical Centre
Cape Town
Western Cape
7500
South Africa
FG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
(Per protocol, placebo arms for Cohorts 1 and 2 were combined for analysis.)
FG003
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5 mg/kg SC once weekly (qwk) for 12 weeks
FG004
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
FG005
Cohort 3 Placebo
Placebo SC qwk for 12 weeks
FG006
Cohort 4 KPL-404 400 mg q4wk
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
FG007
Cohort 4 Placebo
Placebo SC q4wk for 12 weeks
FG0006 subjects
FG0016 subjects
FG0024 subjects
FG00327 subjects
FG00425 subjects
FG00526 subjects
FG00631 subjects
FG00720 subjects
COMPLETED
FG0006 subjects
FG0015 subjects
FG0024 subjects
FG00325 subjects
FG00425 subjects
FG00524 subjects
FG00630 subjects
FG00717 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0032 subjects
FG0040 subjects
FG0052 subjects
FG0061 subjects
FG0073 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
BG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
BG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
BG003
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5 mg/kg SC qwk for 12 weeks
BG004
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
BG005
Cohort 3 Placebo
Placebo SC qwk for 12 weeks
BG006
Cohort 4 KPL-404 400 mg q4wk
KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at Weeks 4 and 8
BG007
Cohort 4 Placebo
Placebo SC q4wk for 12 weeks
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0024
BG00327
BG00425
BG00526
BG00631
BG00720
BG008145
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00056.8± 15.59
BG00156.3± 13.29
BG00259.8± 13.05
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG0005
BG0015
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0014
BG002
Race (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Safety Population: All randomized participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
No
From first dose of study drug to 24 weeks
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC every 2 q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
OG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
Units
Counts
Participants
OG0006
OG0016
OG0024
Title
Denominators
Categories
TEAEs
Title
Measurements
OG0002
OG0012
OG0023
Drug-related TEAEs
Primary
Cohorts 1 and 2: Maximum Serum Concentration (Cmax)
Participants treated with KPL-404, with an evaluable PK sample at given time point.
Posted
Mean
Standard Deviation
µg/mL
Days 1 (Dose 1) and 57 (Dose 4)
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
Units
Counts
Participants
OG000
Primary
Cohorts 1 and 2: Area Under the Serum Concentration-time Curve From Time of Administration to the End of the Dosing Interval, (AUCtau)
Participants treated with KPL-404, with an evaluable PK sample at given time point.
Posted
Mean
Standard Deviation
µg·day/mL
Days 1 (Dose 1) and 57 (Dose 4)
ID
Title
Description
OG000
Cohort 1 KPL-404
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404
KPL-404 5 mg/kg SC q2wk for 12 weeks
Units
Counts
Participants
OG000
Primary
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.
Modified Intent-to-Treat (mITT) population: All randomized participants who received at least one dose of study drug and who had at least one post-baseline assessment for the primary efficacy endpoint.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 12
ID
Title
Description
OG000
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5 mg/kg SC qwk for 12 weeks
OG001
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
OG002
Cohort 3 Placebo
Secondary
Cohorts 1 and 2: Change From Baseline in 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.
mITT Population: All randomized participants who received at least one dose of study drug and who had at least one post-baseline assessment for the primary efficacy endpoint.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 12
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
OG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
Secondary
Cohorts 3 and 4: Number of Participants With 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.
Safety Population: All randomized participants who received at least one dose of study drug.
Posted
Count of Participants
Participants
No
From first dose of study drug to 24 weeks
ID
Title
Description
OG000
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5 mg/kg SC qwk for 12 weeks
OG001
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
Secondary
Cohort 3 and 4: Cmax
Participants treated with KPL-404, with an evaluable PK sample at given time point.
Posted
Mean
Standard Deviation
µg/mL
Days 1 (Dose 1) and 57 (Dose 4 or 8)
ID
Title
Description
OG000
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5mg/kg SC qwk for 12 weeks
OG001
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
OG002
Cohort 4 KPL-404 400 mg q4wk
KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at weeks 4 and 8.
Units
Counts
Participants
OG000
Secondary
Cohort 3 and 4: AUCtau
Participants treated with KPL-404, with an evaluable PK sample at given time point.
Posted
Mean
Standard Deviation
µg·day/mL
Days 1 (Dose 1) and 57 (Dose 4 or 8)
ID
Title
Description
OG000
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5mg/kg SC qwk for 12 weeks
OG001
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
OG002
Cohort 4 KPL-404 400 mg q4wk
KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at weeks 4 and 8.
Units
Counts
Participants
OG000
Secondary
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
An ACR20 response is defined as at least a 20% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 20% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
mITT population: All randomized participants who received at least one dose of study drug and who had at least one post-baseline assessment for the primary efficacy endpoint.
Posted
Number
percentage of participants
Baseline, Week 12
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
OG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
OG003
Cohort 3 KPL-404 5 mg/kg Qwk
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
An ACR50 response is defined as at least a 50% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 50% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
mITT population: All randomized participants who received at least one dose of study drug and who had at least one post-baseline assessment for the primary efficacy endpoint.
Posted
Number
percentage of participants
Baseline, Week 12
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
OG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
OG003
Cohort 3 KPL-404 5 mg/kg Qwk
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
An ACR70 response is defined as at least a 70% improvement in both tender joint count (TJC) and swollen joint count (SJC), and at least a 70% improvement in three of the following five criteria: patient global assessment (PGA), physician global assessment (PhGA), functional ability measure [Health Assessment Questionnaire (HAQ)], patient's assessment of pain (visual analog scale; VAS) and C-reactive protein (CRP).
mITT population: All randomized participants who received at least one dose of study drug and who had at least one post-baseline assessment for the primary efficacy endpoint.
Posted
Number
percentage of participants
Baseline, Week 12
ID
Title
Description
OG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
OG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
OG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
OG003
Cohort 3 KPL-404 5 mg/kg Qwk
Time Frame
Up to 28 weeks
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1 KPL-404 2 mg/kg q2wk
KPL-404 2 mg/kg SC q2wk for 12 weeks
0
6
0
6
2
6
EG001
Cohort 2 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk for 12 weeks
0
6
0
6
3
6
EG002
Cohort 1/2 Placebo
Placebo SC q2wk for 12 weeks
0
4
0
4
3
4
EG003
Cohort 3 KPL-404 5 mg/kg Qwk
KPL-404 5 mg/kg SC qwk for 12 weeks
0
27
1
27
10
27
EG004
Cohort 3 KPL-404 5 mg/kg q2wk
KPL-404 5 mg/kg SC q2wk with alternating weekly administrations of KPL-404 or placebo SC for 12 weeks
0
25
0
25
8
25
EG005
Cohort 3 Placebo
Placebo SC qwk for 12 weeks
0
26
1
26
8
26
EG006
Cohort 4 KPL-404 400 mg q4wk
KPL-404 SC q4wk for 12 weeks: 600 mg loading dose at baseline followed by 400 mg at Weeks 4 and 8
0
31
0
31
10
31
EG007
Cohort 4 Placebo
Placebo SC q4wk for 12 weeks
0
20
0
20
11
20
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sudden hearing loss
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG0031 affected27 at risk
EG0040 affected25 at risk
EG0050 affected26 at risk
EG0060 affected31 at risk
EG0070 affected20 at risk
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Fibrin D dimer increased
Investigations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG0030 affected27 at risk
EG0040 affected25 at risk
EG0051 affected26 at risk
EG0060 affected31 at risk
EG0071 affected20 at risk
Hypertension
Vascular disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Headache
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Fatigue
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Injection site erythema
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Injection site pain
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Prostatitis
Reproductive system and breast disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
COVID-19
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Campylobacter infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0022 affected4 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Animal scratch
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Upper respiratory infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Investigator shall not publish before a first multi-center publication by Sponsor. Before submission, Sponsor has 60 days to review any manuscript and 30 days to review any poster, abstract or any other materials. If Sponsor requests in writing, Investigator shall withhold disclosure for an additional 90 days.