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Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

GSK3196165

MTX

Folic acid

Placebo

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring DMARD-IR, GSK3196165, Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age >=18 years at the time of signing informed consent.
Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks.
Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count).
DAS28(CRP) >=3.2.
CRP >=5.0 milligram per litre (mg/L) at screening.
Must have previously received MTX (15-25 mg weekly) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for >=4 weeks prior to Day 1. A stable dose of MTX >=7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement.
Weight >=45 kilogram (kg).
Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria.
Diffusing capacity of the lung for carbon monoxide (DLCO) >=60% predicted; forced expiratory volume in 1 second (FEV1) >=70% predicted
No evidence of active or latent infection with Mycobacterium tuberculosis (TB).

Exclusion Criteria:

Pregnant or lactating women.
History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren's syndrome secondary to RA.
History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis [PAP]).
Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained.
Significant unstable or uncontrolled acute or chronic disease which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
A history of malignancy.
Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Arm Label

GSK3196165, Dose 1 + MTX and Folic acid

GSK3196165, Dose 2 + MTX and folic acid

GSK3196165, Dose 3 + MTX and folic acid

GSK3196165, Dose 4 + MTX and folic acid

GSK3196165, Dose 5 + MTX and folic acid

Placebo + MTX and folic acid

Arm Description

Subject will receive GSK3196165 Dose 1 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Subject will receive GSK3196165 Dose 2 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Subject will receive GSK3196165 Dose 3 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Subject will receive GSK3196165 Dose 4 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Subject will receive GSK3196165 Dose 5 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved Disease Activity Score for 28 Different Joints With C-reactive Protein Value (DAS28{CRP}) Remission (DAS28 <2.6) at Week 24

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 millimeter [mm] visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in [milligrams/liter] mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). ITT population comprised of all participants who were randomized to treatment and who received at least one dose of study treatment (GSK3196165 or placebo).

Secondary Outcome Measures

Change From Baseline in DAS28(CRP) at Week 12

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant global assessment of disease activity (PtGA) using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points

DAS28(CRP) remission is defined as a DAS28 score of <2.6 points. The DAS index combines information relating to the number of swollen and tender joints. The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome).

Change From Baseline in DAS28(CRP) at All Assessment Time Points

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline.

Time to First DAS28(CRP) Remission

The DAS index combines information relating to the number of swollen and tender joints. The DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Median time, to remission has been presented.

Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points

DAS28(CRP) scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as follows: Current DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2=good response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline value (>1.2 =moderate response), (>0.6 to <=1.2 = moderate response) and (<=0.6 =no response). Current DAS28 >5.1 and DAS28 decrease from Baseline value (>1.2=moderate response), (>0.6 to <=1.2 = no response) and (<=0.6 =no response). If the post-Baseline DAS28(CRP) score was missing, then the corresponding EULAR category was set to missing.

Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points

The ACR definition for calculating improvement in rheumatoid arthritis is calculated as a 20% improvement (ACR20) in both tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: participant and physician global assessments, participant's assessment of arthritis pain, disability, and an acute-phase reactant (i.e. CRP value). Similarly, ACR50 and ACR70 were calculated with the respective percent improvement. The specific components of the ACR assessments are as follows: Tender/Painful Joint count 68 (TJC68), Swollen Joint Count 66 (SJC66), Participant's Assessment of Arthritis Pain, Participant's Global Assessment of Arthritis Disease Activity, Physician's Global Assessment of Arthritis, CRP (mg/L) and Health Assessment Questionnaire - Disability Index (HAQ-DI). For all visits, if any of the component scores were missing, then those scores were considered as not having met the criteria for improvement.

Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points

Index-based remission was achieved if the following requirement was met: SDAI <= 3.3. If the SDAI value was missing at an individual assessment point, Index-based remission for that assessment was set to missing.

Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points

Boolean-based remission was achieved if all of the following requirements were met at the same time: TJC68 <= 1,SJC66 <= 1,CRP <= 1mg/dL, PtGA <= 10. If one of the components was missing at an individual assessment point, Boolean-based remission for that assessment was set to missing.

Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Remission was achieved for a non-missing CDAI value <=2.8.

Change From Baseline in SDAI at All Assessment Time Points

SDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician and acute phase reactants. The SDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal-phalangeal I-V, proximal interphalangeal I-V and knees. It is calculated using the following formula: SDAI = TJC28 + SJC28 + GH + GP + CRP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment, GP= physician assessment of disease activity using a 10 centimetre [cm] visual analogue scale [VAS] with 0 = best, 10 = worst), and CRP= C reactive Protein (in mg/L). It ranges between 0.1 and 86. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in CDAI at All Assessment Time Points

CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points

HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas;dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each functional area contains at least two questions. For each question, there is a four level response set that is scored from 0 (without any difficulty) to 3 (unable to do). If aids or devices or physical assistance are used for a specific functional area and the maximum response of this functional area is 0 or 1 the according value is increased to a score of 2. HAQ-DI is only calculated if there are at least 6 functional area scores available. The average of these non-missing functional area scores defines the continuous HAQ-DI score ranging from 0 to 3. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Pain Score at All Assessment Time Points

Participants assessed the severity of their current arthritis pain using a 100 unit visual analog scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Physical and Mental Component Scores (PCS, MCS) and in Domain Scores of Short Form 36 (SF-36) at All Assessment Time Points

SF-36 is a generic health survey containing 36 questions covering 8 domains of health. SF-36 yields an 8-scale profile of functional health and well-being scores as well as PCS and MCS health summary scores. The version 2, 1-week recall questionnaire was used. Recoding, calculations and standardization were done as per the User's manual of SF-36. Domain scores were only calculated if less than half of the item scores were missing. All raw domain scores were transformed on a 0-100 scale (transformed domain scores) and then standardized into norm-based scores using Z-score. Following the transformation of the 8 domain scores into z-scores, the MCS and PCS were aggregated (AGG) using weights as PCS/MCS = 50 + (AGG_PHYS *10/AGG_MENT *10). High score (worse outcome) and low score (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points

The FACIT-fatigue questionnaire is a participant reported measure developed to assess fatigue consisting of 13 statements regarding feeling fatigue using a numeric rating scale ranging from 0 to 4. For only two of the items (i.e. Answer 5 [An5] and An7) a higher value represents a lower fatigue; 11 of the item scores (i.e. HI7, HI12, An1, An2, An3, An4, An8, An12, An14, An15, An16) have to be reversed by subtracting the captured value from 4 (0 is turned to a 4; 1 into 3; 3 into 1; 4 into 0). After performing the reversals the sum of the non-missing individual items were multiplied by 13 and divided by the number of the non-missing individual items. The final score ranges from 0 to 52 with higher values representing a lower fatigue (i.e. a better quality of life). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points

BFI is a self-reported instrument consisting of nine questions which correlate well with quality-of-life measures. For this study, Question 3 only was used which asked about fatigue severity at its worst in the last 24 hours. A discrete 11 unit numeric reporting scale was used where 0 =No fatigue, and 10=As bad as you can imagine. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per Medical or Scientific judgment. Overall AEs and SAEs for the entire study duration until follow-up have been presented.

Number of Participants With Serious Infections

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious infections were categorized as AE of special interest. The number of participants with overall serious infections have been presented.

Number of Participants With Opportunistic Infections

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Opportunistic infections were categorized as AE of special interest. The number of participants with overall opportunistic infections have been presented.

Number of Participants With Pulmonary Events

Pulmonary assessments were performed to determine the number of participants with pulmonary events including persistent cough, persistent dyspnea, and persistent Diffusing capacity of the lung for carbon monoxide (DLCO). Persistent is defined as any event with duration >=15 days. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants experiencing pulmonary events have been reported.

Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation. Baseline was defined as the last available assessment prior to the start of study treatment. The number of participants with blood oxygen level < 80%, 80% to <90% and >=90% have been reported.

Full Information

NCT ID

NCT02504671

First Posted

July 20, 2015

Last Updated

December 10, 2020

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT02504671

Brief Title

Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

Official Title

A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination With Methotrexate Therapy, in Subjects With Active Moderate-Severe Rheumatoid Arthritis Despite Treatment With Methotrexate

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

July 23, 2015 (Actual)

Primary Completion Date

December 22, 2017 (Actual)

Study Completion Date

December 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a randomised, Phase IIb, dose-adaptive, multicentre, double-blind, parallel group, placebo-controlled study with the primary objective to assess the efficacy of GSK3196165, in combination with methotrexate (MTX), in subjects with active moderate severe rheumatoid arthritis (RA) despite treatment with MTX. Approximately 210 subjects will be randomised into the study, following a screening period of up to four weeks. The total treatment period is up to 52 weeks, with a 12-week follow-up period after the last dose (Week 50). Subjects will be randomised (1:1:1:1:1:1) to placebo or one of five subcutaneous (SC) GSK3196165 doses, in combination with MTX (at a weekly dose between 15-25 milligram [mg]), previously received for at least 12 weeks, with a stable and tolerated dose and route of administration for >=4 weeks. Escape therapy is provided at specified timepoints in the protocol for subjects that do not achieve adequate disease improvement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

DMARD-IR, GSK3196165, Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

222 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK3196165, Dose 1 + MTX and Folic acid

Arm Type

Experimental

Arm Description

Subject will receive GSK3196165 Dose 1 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Arm Title

GSK3196165, Dose 2 + MTX and folic acid

Arm Type

Experimental

Arm Description

Subject will receive GSK3196165 Dose 2 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Arm Title

GSK3196165, Dose 3 + MTX and folic acid

Arm Type

Experimental

Arm Description

Subject will receive GSK3196165 Dose 3 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Arm Title

GSK3196165, Dose 4 + MTX and folic acid

Arm Type

Experimental

Arm Description

Subject will receive GSK3196165 Dose 4 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Arm Title

GSK3196165, Dose 5 + MTX and folic acid

Arm Type

Experimental

Arm Description

Subject will receive GSK3196165 Dose 5 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Arm Title

Placebo + MTX and folic acid

Arm Type

Placebo Comparator

Arm Description

Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid >=5 mg/week.

Intervention Type

Drug

Intervention Name(s)

GSK3196165

Intervention Description

GSK3196165 is supplied as liquid and will be administered as SC injection.

Intervention Type

Drug

Intervention Name(s)

MTX

Intervention Description

MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.

Intervention Type

Drug

Intervention Name(s)

Folic acid

Intervention Description

Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo is supplied as liquid as sterile 0.9% weight by volume (w/v) sodium chloride solution and will be administered as SC injection

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieved Disease Activity Score for 28 Different Joints With C-reactive Protein Value (DAS28{CRP}) Remission (DAS28 <2.6) at Week 24

Description

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Change From Baseline in DAS28(CRP) at Week 12

Description

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant global assessment of disease activity (PtGA) using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time Frame

Baseline and Week 12

Title

Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Change From Baseline in DAS28(CRP) at All Assessment Time Points

Description

DAS28 is a modification of the original DAS and is based on a count of 28 swollen and tender joints and is used to evaluate a participant's response to treatment. DAS 28 CRP utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96. Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity using a 100 mm visual analogue scale with 0 = best, 100 = worst) and CRP= C reactive Protein (in mg/L). It ranges between 0.96 and 8.61. High score (worse outcome) and low scores (better outcome). Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline.

Time Frame

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

Title

Time to First DAS28(CRP) Remission

Description

Time Frame

Up to Week 62

Title

Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission

Description

Time Frame

Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)

Title

Change From Baseline in SDAI at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

Title

Change From Baseline in CDAI at All Assessment Time Points

Description

CDAI combines information relating to the number of swollen and tender joints, in addition to a measure of general health from both the participants and the physician. CDAI utilizing joint scores from the following 28 joints: elbows, shoulders, elbow, wrists, metacarpal- phalangeal I-V, proximal interphalangeal I-V and knees and is calculated using the following formula: CDAI =TJC28 + SJC28 + GH + GP Where TJC - Tender joint Count, SJC= Swollen Joint Count, (GH=participant assessment of disease activity and GP=physician assessment of disease activity using a 10 cm visual analogue scale with 0 = best, 100 = worst). It ranges between 0 and 76. High score indicates worse outcome, low score indicates better outcome. Baseline was defined as the last available assessment prior to the start of study treatment. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Time Frame

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

Title

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24

Title

Change From Baseline in Pain Score at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24

Title

Change From Baseline in Physical and Mental Component Scores (PCS, MCS) and in Domain Scores of Short Form 36 (SF-36) at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 4, 12, 24

Title

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 4, 12, 24

Title

Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points

Description

Time Frame

Baseline and Weeks 4, 12, 24

Title

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

Description

Time Frame

Up to 62 weeks

Title

Number of Participants With Serious Infections

Description

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious infections were categorized as AE of special interest. The number of participants with overall serious infections have been presented.

Time Frame

Up to 62 weeks

Title

Number of Participants With Opportunistic Infections

Description

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Opportunistic infections were categorized as AE of special interest. The number of participants with overall opportunistic infections have been presented.

Time Frame

Up to 62 weeks

Title

Number of Participants With Pulmonary Events

Description

Time Frame

Up to 62 weeks

Title

Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry

Description

Time Frame

Up to 62 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >=18 years at the time of signing informed consent. Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks. Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count). DAS28(CRP) >=3.2. CRP >=5.0 milligram per litre (mg/L) at screening. Must have previously received MTX (15-25 mg weekly) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for >=4 weeks prior to Day 1. A stable dose of MTX >=7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement. Weight >=45 kilogram (kg). Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria. Diffusing capacity of the lung for carbon monoxide (DLCO) >=60% predicted; forced expiratory volume in 1 second (FEV1) >=70% predicted No evidence of active or latent infection with Mycobacterium tuberculosis (TB). Exclusion Criteria: Pregnant or lactating women. History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren's syndrome secondary to RA. History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis [PAP]). Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained. Significant unstable or uncontrolled acute or chronic disease which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk. A history of malignancy. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2 infection.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Plovdiv

ZIP/Postal Code

4000

Country

Bulgaria

Facility Name

GSK Investigational Site

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

GSK Investigational Site

City

Sofia

ZIP/Postal Code

1431

Country

Bulgaria

Facility Name

GSK Investigational Site

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

GSK Investigational Site

City

Brampton

State/Province

Ontario

ZIP/Postal Code

L6T 0G1

Country

Canada

Facility Name

GSK Investigational Site

City

Barrie

ZIP/Postal Code

L4M 6L2

Country

Canada

Facility Name

GSK Investigational Site

City

Brno

ZIP/Postal Code

602 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Bruntal

ZIP/Postal Code

792 01

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

GSK Investigational Site

City

Praha

ZIP/Postal Code

130 00

Country

Czechia

Facility Name

GSK Investigational Site

City

Uherske Hradiste

ZIP/Postal Code

686 01

Country

Czechia

Facility Name

GSK Investigational Site

City

Tallinn

ZIP/Postal Code

10117

Country

Estonia

Facility Name

GSK Investigational Site

City

Tallinn

ZIP/Postal Code

13419

Country

Estonia

Facility Name

GSK Investigational Site

City

Koeln

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

50937

Country

Germany

Facility Name

GSK Investigational Site

City

Bad Doberan

ZIP/Postal Code

18209

Country

Germany

Facility Name

GSK Investigational Site

City

Berlin

ZIP/Postal Code

14059

Country

Germany

Facility Name

GSK Investigational Site

City

Hamburg

ZIP/Postal Code

D-20095

Country

Germany

Facility Name

GSK Investigational Site

City

Budapest

ZIP/Postal Code

1036

Country

Hungary

Facility Name

GSK Investigational Site

City

Kistarcsa

ZIP/Postal Code

2143

Country

Hungary

Facility Name

GSK Investigational Site

City

Veszprém

ZIP/Postal Code

8200

Country

Hungary

Facility Name

GSK Investigational Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20132

Country

Italy

Facility Name

GSK Investigational Site

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

GSK Investigational Site

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

GSK Investigational Site

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44650

Country

Mexico

Facility Name

GSK Investigational Site

City

Cuernavaca

State/Province

Morelos

ZIP/Postal Code

62170

Country

Mexico

Facility Name

GSK Investigational Site

City

Cuernavaca

State/Province

Morelos

ZIP/Postal Code

62290

Country

Mexico

Facility Name

GSK Investigational Site

City

Merida

State/Province

Yucatán

ZIP/Postal Code

97000

Country

Mexico

Facility Name

GSK Investigational Site

City

San Luis Potosí

ZIP/Postal Code

78213

Country

Mexico

Facility Name

GSK Investigational Site

City

Bialystok

ZIP/Postal Code

15-351

Country

Poland

Facility Name

GSK Investigational Site

City

Bydgoszcz

ZIP/Postal Code

85-168

Country

Poland

Facility Name

GSK Investigational Site

City

Bytom

ZIP/Postal Code

41-902

Country

Poland

Facility Name

GSK Investigational Site

City

Grodzisk Mazowiecki

ZIP/Postal Code

05-825

Country

Poland

Facility Name

GSK Investigational Site

City

Lodz

ZIP/Postal Code

91-347

Country

Poland

Facility Name

GSK Investigational Site

City

Lublin

ZIP/Postal Code

20-582

Country

Poland

Facility Name

GSK Investigational Site

City

Torun

ZIP/Postal Code

87-100

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

01-518

Country

Poland

Facility Name

GSK Investigational Site

City

Warszawa

ZIP/Postal Code

02-653

Country

Poland

Facility Name

GSK Investigational Site

City

Moscow

ZIP/Postal Code

119049

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Novosibirsk

ZIP/Postal Code

630099

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Omsk

ZIP/Postal Code

644111

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Ryazan

ZIP/Postal Code

390026

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Saint Petersburg

ZIP/Postal Code

192177

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Tver

ZIP/Postal Code

170036

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Vladimir

ZIP/Postal Code

600023

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Yaroslavl

ZIP/Postal Code

150003

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Yaroslavl

ZIP/Postal Code

150023

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

Country

South Africa

Facility Name

GSK Investigational Site

City

Panorama / Cape Town

ZIP/Postal Code

7500

Country

South Africa

Facility Name

GSK Investigational Site

City

Stellenbosch

ZIP/Postal Code

7600

Country

South Africa

Facility Name

GSK Investigational Site

City

Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

GSK Investigational Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

GSK Investigational Site

City

Ivano-Frankivsk

ZIP/Postal Code

76008

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kharkiv

ZIP/Postal Code

61029

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kharkiv

ZIP/Postal Code

61039

Country

Ukraine

Facility Name

GSK Investigational Site

City

Kryvyi Rih

ZIP/Postal Code

50056

Country

Ukraine

Facility Name

GSK Investigational Site

City

Lviv

ZIP/Postal Code

79013

Country

Ukraine

Facility Name

GSK Investigational Site

City

Odesa

ZIP/Postal Code

65026

Country

Ukraine

Facility Name

GSK Investigational Site

City

Poltava

ZIP/Postal Code

36011

Country

Ukraine

Facility Name

GSK Investigational Site

City

Sumy

ZIP/Postal Code

40022

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsia

ZIP/Postal Code

21018

Country

Ukraine

Facility Name

GSK Investigational Site

City

Vinnytsya

ZIP/Postal Code

21029

Country

Ukraine

Facility Name

GSK Investigational Site

City

Zhytomyr

ZIP/Postal Code

10002

Country

Ukraine

Facility Name

GSK Investigational Site

City

Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Leeds

ZIP/Postal Code

LS7 4SA

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study is available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20744

Citations:

Citation

C Buckley, J Simon Campos, V Zhdan, K Davy, D Inman, E Fisheleva, A Gupta, M Layton, N Mitchell, J Patel, R Williamson, D Saurigny, P-P Tak, C Hawkes, B Becker. A Phase IIb Dose-Ranging Randomised Study of Efficacy, Patient-Reported Outcomes and Safety of the Anti-Granulocyte Macrophage Colony-Stimulating Factor Antibody Otilimab (GSK3196165) in Patients with Rheumatoid Arthritis. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30229-0

Results Reference

background

Learn more about this trial

Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

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Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

Arthritis, Rheumatoid

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial