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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01198002




Registration number
NCT01198002
Ethics application status
Date submitted
8/09/2010
Date registered
9/09/2010
Date last updated
8/05/2018

Titles & IDs
Public title
A Rheumatoid Arthritis Study in Participants on a Background Treatment of Methotrexate
Scientific title
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients With Moderate to Severe Rheumatoid Arthritis (RA) Who Had an Inadequate Response to Methotrexate Therapy (FLEX M)
Secondary ID [1] 0 0
H9B-MC-BCDM
Secondary ID [2] 0 0
11352
Universal Trial Number (UTN)
Trial acronym
FLEX M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY2127399
Treatment: Drugs - Placebo Q2W
Treatment: Drugs - Placebo Q4W
Treatment: Drugs - Methotrexate

Experimental: 120 milligrams (mg) LY2127399 - Given every 4 weeks (Q4W) for 100 weeks. Participants receive a 240 mg loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks (Q2W).

At Weeks 16 and 52, responders will receive 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 100-week treatment period.

At Week 16, non-responders (NR) will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Experimental: 90 mg LY2127399 - Given Q2W for 100 weeks. Participants receive a 180 mg loading dose when initiating treatment.

At Weeks 16 and 52, responders will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q4W for the rest of the 100-week treatment period.

At Week 16, NR will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Placebo comparator: Placebo - Given Q2W for 52 weeks. At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 52 weeks.

At Week 52, responders are randomized to receive 1 of the 2 doses of LY2127399, with loading dose of 240 mg or 180 mg of LY2127399, followed by 120 mg of LY2127399 Q4W or 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

At Week 16, NR will receive a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.


Treatment: Drugs: LY2127399
Administered Subcutaneously (SC)

Treatment: Drugs: Placebo Q2W
Administered SC

Treatment: Drugs: Placebo Q4W
Administered SC

Treatment: Drugs: Methotrexate
Methotrexate is a background therapy.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With American College of Rheumatology 20% Response (ACR20) at Week 24
Assessment method [1] 0 0
ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had =20% improvement from baseline in both 68 tender and 66 swollen joint counts and =20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders) / (number of participants treated) \* 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 24 endpoint.
Timepoint [1] 0 0
Baseline through 24 weeks
Primary outcome [2] 0 0
Change From Baseline to Week 52 in Van Der Heijde Modified Total Sharp Score (mTSS)
Assessment method [2] 0 0
The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range = 0 to 220 for 44 joints) and narrowing scores (range = 0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 \[normal\] to 388 \[maximal disease\]). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate.
Timepoint [2] 0 0
Baseline, 52 Weeks
Primary outcome [3] 0 0
Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Assessment method [3] 0 0
The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [3] 0 0
Baseline, 24 weeks
Secondary outcome [1] 0 0
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
Assessment method [1] 0 0
ACR Responder Index: Composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had =50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and =50% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No.) of ACR50 responders) / (No. of Pts treated) \* 100. ACR70 Responder: had =70% improvement from baseline in both TJ and SJ counts and =70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response= (No. of ACR70 responders) / (No. of Pts treated) \* 100. All NR at Week 16 as well as all Pts who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Weeks 24 and 52 endpoints.
Timepoint [1] 0 0
Baseline through 24 weeks and 52 weeks
Secondary outcome [2] 0 0
Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)
Assessment method [2] 0 0
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and participant's global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [2] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [3] 0 0
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response
Assessment method [3] 0 0
EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response =(number of participants with specific response) / (number of participants analyzed in the group) \* 100.
Timepoint [3] 0 0
Baseline through 24 weeks and 52 weeks
Secondary outcome [4] 0 0
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores
Assessment method [4] 0 0
SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores were calculated by summing each item for each domain and transforming scores into a 0-100 scale. Higher scores indicated better health status. If \< 50% of the questions within a domain were answered, raw scores were not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100. Higher score indicated better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate.
Timepoint [4] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [5] 0 0
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score
Assessment method [5] 0 0
The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, Item 1 is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0=no fatigue and 10=fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [5] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [6] 0 0
Change From Baseline in Duration of Morning Stiffness (Minutes)
Assessment method [6] 0 0
The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [6] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [7] 0 0
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores
Assessment method [7] 0 0
The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24-hours and pain based on the pain right now with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in past 24-hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life \[each item scored from 0 (does not interfere) to 10 (completely interferes)\]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score were set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [7] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [8] 0 0
Percentage of Participants With Major Clinical Response (MCR) During 52 Weeks
Assessment method [8] 0 0
Timepoint [8] 0 0
Baseline through 52 weeks
Secondary outcome [9] 0 0
Percentage of Participants With Change From Baseline in mTSS Less Than or Equal to (=) 0
Assessment method [9] 0 0
The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 \[normal\] to 388 \[maximal disease\]). Percentage of participants = (number of participants with mTSS =0 at Week 24) / (total number of participants analyzed in the group) \* 100.
Timepoint [9] 0 0
Baseline through 24 weeks
Secondary outcome [10] 0 0
Change From Baseline to Week 52 in B Cell Subset Counts
Assessment method [10] 0 0
B cell subset counts are: cluster designation (CD)19+ B cell counts, Immature/transitional \[CD19+immunoglobulin D (IgD)-CD27-\], Mature naïve (CD19+IgD+CD27-), Non-switched memory (CD19+IgD+CD27+) and Memory (CD19+IgD-CD27+). A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [10] 0 0
Baseline, 52 weeks
Secondary outcome [11] 0 0
Population Pharmacokinetics (PK): Constant Clearance
Assessment method [11] 0 0
Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.
Timepoint [11] 0 0
Baseline through 52 weeks
Secondary outcome [12] 0 0
Percentage of Participants Developing Anti-LY2127399 Antibodies
Assessment method [12] 0 0
Participants with treatment-emergent anti-drug antibodies (ADA) were participants who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of =1:20). Percentage of participants with ADA=(number of participants with treatment-emergent ADA) / (number of participants assessed) \* 100.
Timepoint [12] 0 0
Baseline through 52 weeks
Secondary outcome [13] 0 0
Percentage of Participants With No Structural Progression at Week 52
Assessment method [13] 0 0
No structural progression is defined as the change in mTSS from baseline =0. The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 \[normal\] to 388 \[maximal disease\]). Percentage of participants=(number of participants with mTSS =0 at Week 52) / (total number of participants analyzed in the group) \* 100.
Timepoint [13] 0 0
Baseline through 52 weeks
Secondary outcome [14] 0 0
Change From Baseline to Week 24 in mTSS
Assessment method [14] 0 0
The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 \[normal\] to 388 \[maximal disease\]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [14] 0 0
Baseline, 24 weeks
Secondary outcome [15] 0 0
Change From Baseline in Serum Immunoglobulin (Ig) Levels
Assessment method [15] 0 0
Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [15] 0 0
Baseline, 52 weeks
Secondary outcome [16] 0 0
Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS)
Assessment method [16] 0 0
The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 \[normal\] to 388 \[maximal disease\]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [16] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [17] 0 0
American College of Rheumatology Percent Improvement (ACR-N)
Assessment method [17] 0 0
ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJ count, b) % change in SJ count, or c) the median % change of remaining 5 ACR core criteria: If =3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline DAS28-CRP as a covariate.
Timepoint [17] 0 0
Baseline through 24 weeks and 52 weeks
Secondary outcome [18] 0 0
Change From Baseline in Tender Joint Count (68 Joint Count)
Assessment method [18] 0 0
Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [18] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [19] 0 0
Change From Baseline in Swollen Joint Count (66 Joint Count)
Assessment method [19] 0 0
Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [19] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [20] 0 0
Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]
Assessment method [20] 0 0
Participant's assessment of their current arthritis pain using VAS ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [20] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [21] 0 0
Change From Baseline in Participant's Global Assessment of Disease Activity (VAS)
Assessment method [21] 0 0
Participant's assessment of their current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [21] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [22] 0 0
Change From Baseline in Physician's Global Assessment of Disease Activity (VAS)
Assessment method [22] 0 0
Physician's assessment of the participant's current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [22] 0 0
Baseline, 24 weeks and 52 weeks
Secondary outcome [23] 0 0
Change From Baseline to Week 52 in HAQ-DI
Assessment method [23] 0 0
The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [23] 0 0
Baseline, 52 weeks
Secondary outcome [24] 0 0
Change From Baseline to Week 52 in Absolute B Cell Counts
Assessment method [24] 0 0
Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [24] 0 0
Baseline, 52 weeks
Secondary outcome [25] 0 0
Percentage of Participants With ACR20 at Week 52
Assessment method [25] 0 0
ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had =20% improvement from baseline in both 68 tender and 66 swollen joint counts and =20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR20 response=(number of ACR20 responders) /( number of participants treated) \* 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 52 endpoint.
Timepoint [25] 0 0
Baseline through 52 weeks
Secondary outcome [26] 0 0
Time to ACR20 Response
Assessment method [26] 0 0
ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had =20% improvement from baseline in both 68 tender and 66 swollen joint counts and =20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. The Kaplan-Meier was used to estimate time to ACR20 response over the Treatment Period (52 weeks). Time to ACR20 response = (Date of the first post-baseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7. Week 16 NR are counted as responders if they responded prior to Week 16. Otherwise, they are censored at the date of the Week 16 injection. All participants ongoing at Week 52 and had not yet responded are censored at the date of the Week 52 visit.
Timepoint [26] 0 0
Baseline through 52 weeks
Secondary outcome [27] 0 0
Change From Baseline in CRP
Assessment method [27] 0 0
CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Timepoint [27] 0 0
Baseline, 24 weeks and 52 weeks

Eligibility
Key inclusion criteria
* Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
* Regular use of methotrexate (MTX) in the past 12 weeks, with the dose being stable during the past 8 weeks
* At least 8 tender and swollen joints
* At least one erosion of a hand or foot joint observed on an X-ray
* An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR)
* Positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody
* Woman must not be pregnant, breastfeeding, or become pregnant during the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of unstable doses of non-steroidal anti-inflammatory drugs (NSAIDS) in the past 6 weeks
* Steroid injection or intravenous (iv) infusion in the last 6 weeks
* Use of more than 10 milligrams/day (mg/day) of oral steroids in the last 6 weeks
* History of an inadequate response to a biologic disease-modifying anti-rheumatic drug (DMARD)
* History of a serious reaction to other biological DMARDs
* History of the use of rituximab or other B cell therapy
* Use of DMARDS other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
* Use of leflunomide within the last 12 weeks (unless cholestyramine was used to speed up the elimination of leflunomide)
* Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study
* Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA
* Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years
* Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)
* Hepatitis or human immunodeficiency virus (HIV)
* A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months
* Symptoms of herpes zoster or herpes simplex within the last month
* Active or latent tuberculosis (TB)
* Current symptoms of a serious disorder or illness
* Use of an investigational drug within the last month
* History of the use of rituximab, any other B cell targeted biotherapy, or denosumab

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2014
Sample size
Target
Accrual to date
Final
1041
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Campbelltown
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Herston
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Malvern East
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3145 - Malvern East
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Vinnytsya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01198002