Rheumatoid Arthritis
Conditions
Keywords
rheumatoid arthritis, RA
Brief summary
The primary purpose of the study is to help answer the following research questions, and not to provide treatment for Rheumatoid Arthritis (RA): * The safety of LY2439821 and any side effects that might be associated with it. * Whether LY2439821 can help participants with active RA. * How much LY2439821 should be given to participants.
Detailed description
Study I1F-MC-RHAK is a multicenter study in participants with active RA on concomitant conventional DMARD therapy. The study is a Phase 2 study with 2 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design and Part B is an optional, open-label extension design. Two participant populations will be evaluated in this study: bDMARD-naive participants and TNFα-IR participants. Participants in Part A receive multiple subcutaneous injections of LY2439821 \[bDMARD-naive participants: 0 (placebo), 3, 10, 30, 80, or 180 mg; TNFα-IR participants: 0 (placebo), 80 or 180 mg\] at Weeks 0, 1, 2, 4, 6, 8, and 10. Participants in Part B receive subcutaneous injections of LY2439821 160 mg at Weeks 16, 18, and 20, and every 4 weeks thereafter through Week 60. Participants who complete both Part A and B have a total study participation of up to approximately 72 to 84 weeks.
Interventions
BIOLOGICALLY2439821
Subcutaneous
DRUGPlacebo
Subcutaneous
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* You must be between the ages of 18 and 75 * You must have active RA Qualifications Specific to the bDMARD-naive Population: You must be regularly using methotrexate (MTX) for at least 12 weeks before your participation in this study Qualifications Specific to the TNFα-IR Population: * You must have been treated with at least 1 biologic TNFα inhibitor therapy and either had an insufficient response to at least 3 months of treatment OR have been intolerant of such treatment * You must be regularly using at least 1 conventional DMARD in a stable treatment regimen
Exclusion criteria
* You are concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 2 weeks * You are a woman who is lactating or breast feeding * You have donated more than 300 milliliters (mL) of blood within the last month * You have received glucocorticoid administered by intra-articular, intramuscular, or intravenous injection or oral corticosteroids at an average daily dose of greater than 10 mg per day of prednisone or its equivalent within the last 4 weeks * You had surgery on a joint that is to be assessed in the study within 2 months of study enrollment, or will require such during the study * You have another serious disorder or illness * You suffered a serious bacterial infection (for example, pneumonia, cellulitis, or bone or joint infections) within the last 3 months * You have a history of uncontrolled high blood pressure * You have clinical laboratory test results at entry that are outside the normal reference range * You are an employee of the clinic or you are an immediate family member of an employee of the clinic. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted * You are currently participating in or were discontinued within the last 30 days from another clinical trial involving an investigational drug * If you are a woman and you could become pregnant during this study, you must talk to the study doctor about the birth control that you will use to avoid getting pregnant during the study. * If you are a post-menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months * If you are a post-menopausal woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test to see if you can participate. * If you are male, you must agree to reduce the risk of your female partner becoming pregnant during the study. Exclusions Specific to the bDMARD-naive Population: * You have received any prior bDMARD therapy such as TNFα, Interleukin (IL)-1, IL-6, T-cell, or B-cell targeted therapies * You have had an inadequate response to a minimum of 3 months of treatment with 5 or more conventional DMARDs \[such as leflunomide, azathioprine, cyclosporine, etcetera (etc.)\] * You have used DMARDs other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks * You have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body. Exclusions Specific to the TNFα-IR Population: * You are currently using or recently used a bDMARD or a biologic TNFα inhibitor therapy within specified periods * You have had a serious reaction to other biologic DMARDs that, in the study doctor's opinion, puts you at serious risk * You have used cyclosporine or any other immunosuppressive in the 8 weeks before your participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | Week 12 | ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), Patient's Global Assessment of Disease Activity-VAS(PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI). Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population | Week 12 | ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. The model used in the dose response analysis was used to estimate the doses that achieved 10%, 50%, and 90% of the maximal drug efficacy. Missing values were imputed using NRI. The log transformed dose was evaluated. |
| Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population | Week 12 | DAS modified included the 28 diarthrodial joint count (DAS28) that consisted of a composite score of the following variables: TJC out of 28 (TJC28), SJC out of 28 (SJC28), CRP \[milligrams per liter (mg/L)\], and PtGADA on a 0 to 100 millimeter (mm) VAS ranging from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 was calculated as: DAS28 - CRP = 0.56(square root of TJC28) + 0.28(square root of SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96. |
| Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population | Week 12 | ACR50 responders were participants with at least 50% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. |
| Change From Baseline in Disease Activity Score (DAS28)-Part A | Baseline, up to Week 12 | DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 - CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96. A negative change indicated an improvement. |
| Change From Baseline in DAS28 - Part B | Baseline, Week 64 | DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 - CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96. A negative change indicated an improvement. |
| Percentage of Participants With ACR20/50/70 Response - Part A | Week 12 | ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70%, respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 \[or ACR50 or ACR70\] responders per treatment arm) / (total number of participants per treatment arm) \* 100. |
| Percentage of Participants With of ACR20/50/70 Response - Part B | Week 64 | ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70% respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 \[or ACR50 or ACR70\] responders per treatment arm) / (total number of participants per treatment arm) \* 100\]. |
| Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | Baseline, up to Week 12 | TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints. |
| Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | Baseline, Week 64 | TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints. |
| Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | Baseline, up to Week 12 | SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints count ranged from 0-28. A negative change indicated fewer swollen joints. |
| Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | Baseline, Week 64 | SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints ranged from 0-28. A negative change indicated fewer swollen joints. |
| Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | Baseline, up to Week 12 | Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as no pain and the right end (100 mm) marked worst possible pain. The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain. |
| Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | Baseline, Week 64 | Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as no pain and the right end (100 mm) marked worst possible pain. The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain. |
| Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | Baseline, up to Week 12 | The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity to the right end (100 mm) marked extremely active arthritis. A negative change indicated an improvement in the participant's assessment of disease activity. |
| Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | Baseline, Week 64 | The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity to the right end (100 mm) marked extremely active arthritis. A negative change indicated an improvement in the participant's assessment of disease activity. |
| Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | Baseline, up to Week 12 | The investigator gave an overall assessment of the severity of the participants disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity and the right end (100 mm) marked as extremely active arthritis. A negative change indicated a lessening in the severity of the participant's disease activity. |
| Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | Baseline, Week 64 | The investigator gave an overall assessment of the severity of the participant's disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity and the right end (100 mm) marked as extremely active arthritis. A negative change indicated a lessening in the severity of the participant's disease activity. |
| Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population | Week 12 | ACR20 responders were participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) \* 100. |
| Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | Baseline, Week 64 | CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity. |
| Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | Week 12 | Assessment of participant's rheumatoid arthritis (RA) by the EULAR that is based on the DAS 28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) \* 100. |
| Percentage of Participants in EULAR28 - Part B | Week 64 | Assessment of participant's RA by the EULAR that is based on the DAS28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) \* 100. |
| ACR-N - Part A | Week 12 | ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: \[(post baseline value - baseline value) / baseline value\] \* 100. |
| ACR-N - Part B | Week 64 | ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: \[(post baseline value - baseline value)/baseline value\] \* 100. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | Baseline, up to Week 12 | The FACIT Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue. |
| Change From Baseline in FACIT Fatigue Scale - Part B | Baseline, Week 64 | The FACIT-Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue. |
| Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | Baseline, up to Week 12 | The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement. |
| Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | Baseline, Week 64 | The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement. |
| Change From Baseline in HAQ-DI - Part A | Baseline, up to Week 12 | HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range of 0 to 3. Negative mean changes from baseline indicated improvement. |
| Change From Baseline in HAQ-DI - Part B | Baseline, Week 64 | HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement. |
| Relationship Between Exposure and Response of Individual Components of the ACR Core Set | Through Week 72 | — |
| Relationship Between Exposure and Response of ACR20/50/70/N | Through Week 72 | — |
| Relationship Between Exposure and Response of DAS28 | Through Week 72 | — |
| Relationship Between Exposure and Response of EULAR28 | Through Week 72 | — |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | Predose: Day 0, Day 1 or 2 or 3, Day 7, Weeks 6, 10, 16, 40 and 64 and Postdose: Day 0 and Week 6 | Evaluable PK concentrations from all time points, including data from placebo participants who elected active treatment in Part B, were combined and utilized in a population approach to determine the population median estimates and 90% confidence intervals at steady state. Day 0 and Week 6 postdose samples were collected as late as possible during the dosing visit (in other words, the postdose samples were collected at the end of their respective visits). |
| Percentage of Participants With Anti-LY2439821 Antibodies | Week 16, Week 64 | Treatment-emergent anti-LY2439821 antibody positive participants were defined as a titer change from baseline that was at least 2 dilutions (4-fold) increase. Participants must have had an assessment to be classified as treatment emergent antibody positive or negative. |
| Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | Baseline, up to Week 12 | CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity. |
Countries
Argentina, Chile, Germany, India, Peru, Poland, Romania, Russia, South Korea, Taiwan, United States
Participant flow
Pre-assignment details
Participants were randomized to Part A and had the option of continuing in the open-label extension, Part B after completing Part A.
Participants by arm
| Arm | Count |
|---|---|
| Placebo [bDMARD-naive Population] Placebo administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 54 |
| 3 mg LY2439821 [bDMARD-naive Population] 3 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 40 |
| 10 mg LY2439821 [bDMARD-naive Population] 10 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 35 |
| 30 mg LY2439821 [bDMARD-naive Population 30 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 37 |
| 80 mg LY2439821 [bDMARD-naive Population] 80 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 57 |
| 180 mg LY2439821[bDMARD-naive Population] 180 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 37 |
| Placebo [TNFα-IR Population] Placebo administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 64 |
| 80 mg LY2439821 [TNFα-IR Population] 80 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 65 |
| 180 mg LY2439821 [TNFα-IR Population] 180 mg LY2439821 administered subcutaneously at Weeks 0, 1, 2, 4, 6, 8 and 10 in Part A, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. | 59 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part A | Adverse Event | 2 | 1 | 0 | 1 | 0 | 1 | 0 | 3 | 3 |
| Part A | Entry Criteria | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Part A | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 4 | 0 | 0 |
| Part A | Lost to Follow-up | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part A | Parent/Caregiver Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 |
| Part A | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 |
| Part A | Sponsor Decision | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 1 |
| Part A | Withdrawal by Subject | 2 | 2 | 1 | 1 | 3 | 0 | 5 | 1 | 1 |
| Part B | Adverse Event | 0 | 1 | 1 | 0 | 1 | 0 | 5 | 2 | 2 |
| Part B | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part B | Entry Criteria | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Part B | Lack of Efficacy | 2 | 1 | 1 | 1 | 2 | 3 | 12 | 9 | 6 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Part B | Physician Decision | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 0 | 2 |
| Part B | Sponsor Decision | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 |
| Part B | Withdrawal by Subject | 2 | 1 | 2 | 1 | 2 | 1 | 4 | 5 | 5 |
Baseline characteristics
| Characteristic | 10 mg LY2439821 [bDMARD-naive Population] | 30 mg LY2439821 [bDMARD-naive Population | 80 mg LY2439821 [bDMARD-naive Population] | 180 mg LY2439821[bDMARD-naive Population] | Placebo [bDMARD-naive Population] | Placebo [TNFα-IR Population] | 80 mg LY2439821 [TNFα-IR Population] | 3 mg LY2439821 [bDMARD-naive Population] | 180 mg LY2439821 [TNFα-IR Population] | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 8 Participants | 9 Participants | 5 Participants | 9 Participants | 5 Participants | 10 Participants | 3 Participants | 7 Participants | 61 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 29 Participants | 48 Participants | 32 Participants | 45 Participants | 59 Participants | 55 Participants | 37 Participants | 52 Participants | 387 Participants |
| Age, Continuous | 53.86 years STANDARD_DEVIATION 10.62 | 53.03 years STANDARD_DEVIATION 12.16 | 52.60 years STANDARD_DEVIATION 10.91 | 52.21 years STANDARD_DEVIATION 11.33 | 52.99 years STANDARD_DEVIATION 10.18 | 53.19 years STANDARD_DEVIATION 10.44 | 54.74 years STANDARD_DEVIATION 11.12 | 52.19 years STANDARD_DEVIATION 9.67 | 52.43 years STANDARD_DEVIATION 9.9 | 53.08 years STANDARD_DEVIATION 10.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 7 Participants | 10 Participants | 6 Participants | 9 Participants | 15 Participants | 23 Participants | 7 Participants | 15 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 29 Participants | 46 Participants | 30 Participants | 45 Participants | 48 Participants | 41 Participants | 32 Participants | 43 Participants | 338 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 16 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 12 Participants | 17 Participants | 10 Participants | 16 Participants | 3 Participants | 4 Participants | 13 Participants | 3 Participants | 88 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants | 6 Participants | 2 Participants | 2 Participants | 4 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 20 Participants | 31 Participants | 22 Participants | 29 Participants | 54 Participants | 58 Participants | 20 Participants | 50 Participants | 305 Participants |
| Region of Enrollment Argentina | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 10 participants | 11 participants | 0 participants | 10 participants | 34 participants |
| Region of Enrollment Chile | 2 participants | 0 participants | 2 participants | 2 participants | 0 participants | 1 participants | 2 participants | 1 participants | 1 participants | 11 participants |
| Region of Enrollment Germany | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 3 participants | 2 participants | 0 participants | 2 participants | 8 participants |
| Region of Enrollment India | 6 participants | 7 participants | 11 participants | 6 participants | 9 participants | 0 participants | 0 participants | 7 participants | 0 participants | 46 participants |
| Region of Enrollment Korea, Republic of | 1 participants | 1 participants | 2 participants | 1 participants | 2 participants | 2 participants | 3 participants | 2 participants | 2 participants | 16 participants |
| Region of Enrollment Peru | 4 participants | 4 participants | 6 participants | 4 participants | 6 participants | 1 participants | 1 participants | 4 participants | 1 participants | 31 participants |
| Region of Enrollment Poland | 8 participants | 7 participants | 9 participants | 7 participants | 11 participants | 11 participants | 11 participants | 8 participants | 10 participants | 82 participants |
| Region of Enrollment Romania | 3 participants | 4 participants | 6 participants | 3 participants | 5 participants | 1 participants | 1 participants | 4 participants | 0 participants | 27 participants |
| Region of Enrollment Russian Federation | 0 participants | 1 participants | 3 participants | 2 participants | 3 participants | 1 participants | 1 participants | 1 participants | 1 participants | 13 participants |
| Region of Enrollment Taiwan | 3 participants | 4 participants | 4 participants | 3 participants | 5 participants | 1 participants | 1 participants | 4 participants | 1 participants | 26 participants |
| Region of Enrollment United States | 8 participants | 8 participants | 12 participants | 9 participants | 12 participants | 33 participants | 32 participants | 9 participants | 31 participants | 154 participants |
| Sex: Female, Male Female | 27 Participants | 31 Participants | 52 Participants | 30 Participants | 47 Participants | 55 Participants | 57 Participants | 33 Participants | 51 Participants | 383 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 5 Participants | 7 Participants | 7 Participants | 9 Participants | 8 Participants | 7 Participants | 8 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 40 | 16 / 35 | 16 / 37 | 23 / 57 | 16 / 37 | 22 / 54 | 31 / 65 | 32 / 59 | 32 / 64 | 14 / 36 | 19 / 33 | 12 / 34 | 23 / 51 | 16 / 32 | 26 / 46 | 23 / 57 | 16 / 50 | 23 / 51 |
| serious Total, serious adverse events | 0 / 40 | 1 / 35 | 1 / 37 | 4 / 57 | 1 / 37 | 1 / 54 | 5 / 65 | 6 / 59 | 1 / 64 | 3 / 36 | 3 / 33 | 2 / 34 | 4 / 51 | 1 / 32 | 4 / 46 | 7 / 57 | 4 / 50 | 7 / 51 |
Outcome results
Primary
Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population
ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), Patient's Global Assessment of Disease Activity-VAS(PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI). Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) \* 100.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug and were bDMARD-naive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 34.1 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 46.2 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 52.2 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 55.0 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 55.3 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population | 54.0 percentage of participants |
p-value: 0.031Regression, Logistic
Secondary
ACR-N - Part A
ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: \[(post baseline value - baseline value) / baseline value\] \* 100.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug with results at Week 12; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | ACR-N - Part A | -11.034 units on a scale | Standard Deviation 104.809 |
| 3 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part A | -0.699 units on a scale | Standard Deviation 139786 |
| 10 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part A | 15.162 units on a scale | Standard Deviation 51.13 |
| 30 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part A | 11.137 units on a scale | Standard Deviation 128.516 |
| 80 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part A | 18.351 units on a scale | Standard Deviation 41.493 |
| 180 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part A | 23.375 units on a scale | Standard Deviation 42.173 |
| Placebo (TNFα-IR Population) | ACR-N - Part A | -7.356 units on a scale | Standard Deviation 45.724 |
| 80 mg LY2439821 (TNFα-IR Population) | ACR-N - Part A | 2.264 units on a scale | Standard Deviation 59.277 |
| 180 mg LY2439821 (TNFα-IR Population) | ACR-N - Part A | 11.541 units on a scale | Standard Deviation 49.358 |
p-value: 0.307ANCOVA
p-value: 0.104ANCOVA
p-value: 0.139ANCOVA
p-value: 0.056ANCOVA
p-value: 0.048ANCOVA
p-value: 0.16ANCOVA
p-value: 0.029ANCOVA
Secondary
ACR-N - Part B
ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: \[(post baseline value - baseline value)/baseline value\] \* 100.
Time frame: Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 ACR-N results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | ACR-N - Part B | 36.839 units on a scale | Standard Deviation 42.241 |
| 3 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part B | 33.154 units on a scale | Standard Deviation 32.439 |
| 10 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part B | 39.922 units on a scale | Standard Deviation 37.93 |
| 30 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part B | 34.847 units on a scale | Standard Deviation 69.41 |
| 80 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part B | 38.996 units on a scale | Standard Deviation 30.715 |
| 180 mg LY2439821 (bDMARD-naive Population) | ACR-N - Part B | 49.152 units on a scale | Standard Deviation 31.544 |
| Placebo (TNFα-IR Population) | ACR-N - Part B | 22.230 units on a scale | Standard Deviation 54.682 |
| 80 mg LY2439821 (TNFα-IR Population) | ACR-N - Part B | 14.389 units on a scale | Standard Deviation 45.461 |
| 180 mg LY2439821 (TNFα-IR Population) | ACR-N - Part B | 30.891 units on a scale | Standard Deviation 41.415 |
Secondary
Change From Baseline in DAS28 - Part B
DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 - CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96. A negative change indicated an improvement.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 DAS28 results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -2.143 units on a scale | Standard Deviation 1.177 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -1.832 units on a scale | Standard Deviation 1.031 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -2.320 units on a scale | Standard Deviation 1.292 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -2.277 units on a scale | Standard Deviation 1.337 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -2.280 units on a scale | Standard Deviation 1.316 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in DAS28 - Part B | -2.475 units on a scale | Standard Deviation 1.14 |
| Placebo (TNFα-IR Population) | Change From Baseline in DAS28 - Part B | -1.740 units on a scale | Standard Deviation 1.46 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in DAS28 - Part B | -1.604 units on a scale | Standard Deviation 1.282 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in DAS28 - Part B | -1.874 units on a scale | Standard Deviation 1.279 |
Secondary
Change From Baseline in Disease Activity Score (DAS28)-Part A
DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 - CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96. A negative change indicated an improvement.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -0.818 units on a scale | Standard Deviation 0.981 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.308 units on a scale | Standard Deviation 1.092 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.565 units on a scale | Standard Deviation 1.44 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.671 units on a scale | Standard Deviation 1.193 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.686 units on a scale | Standard Deviation 1.344 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.940 units on a scale | Standard Deviation 1.152 |
| Placebo (TNFα-IR Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -0.619 units on a scale | Standard Deviation 1.109 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.310 units on a scale | Standard Deviation 1.303 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Disease Activity Score (DAS28)-Part A | -1.571 units on a scale | Standard Deviation 1.261 |
p-value: 0.013ANCOVA
p-value: 0.004ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A
The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -36.6 minutes | Standard Deviation 123.7 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -24.3 minutes | Standard Deviation 87.3 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -52.7 minutes | Standard Deviation 142 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -71.4 minutes | Standard Deviation 143.9 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -63.0 minutes | Standard Deviation 57 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -69.0 minutes | Standard Deviation 64.1 |
| Placebo (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -36.3 minutes | Standard Deviation 137.7 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -62.0 minutes | Standard Deviation 138.1 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A | -43.1 minutes | Standard Deviation 116.7 |
p-value: 0.982ANCOVA
p-value: 0.276ANCOVA
p-value: 0.05ANCOVA
p-value: 0.01ANCOVA
p-value: 0.046ANCOVA
p-value: 0.017ANCOVA
p-value: 0.066ANCOVA
Secondary
Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B
The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 Duration of Morning Stiffness results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -92.1 minutes | Standard Deviation 111.3 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -70.2 minutes | Standard Deviation 112.3 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -55.6 minutes | Standard Deviation 72.9 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -92.3 minutes | Standard Deviation 136.7 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -68.8 minutes | Standard Deviation 72.5 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -82.3 minutes | Standard Deviation 79.2 |
| Placebo (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -61.3 minutes | Standard Deviation 161.9 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -60.9 minutes | Standard Deviation 164.7 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B | -85.9 minutes | Standard Deviation 74.8 |
Secondary
Change From Baseline in FACIT Fatigue Scale - Part B
The FACIT-Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 FACIT results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 8.390 units on a scale | Standard Deviation 8.405 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 4.879 units on a scale | Standard Deviation 10.81 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 8.500 units on a scale | Standard Deviation 12.88 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 9.177 units on a scale | Standard Deviation 11.637 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 7.295 units on a scale | Standard Deviation 10.436 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 6.038 units on a scale | Standard Deviation 9.986 |
| Placebo (TNFα-IR Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 8.323 units on a scale | Standard Deviation 9.304 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 4.341 units on a scale | Standard Deviation 8.493 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in FACIT Fatigue Scale - Part B | 6.647 units on a scale | Standard Deviation 9.639 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A
The FACIT Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue.
Time frame: Baseline, up to Week 12
Population: Part A FAS: defined as all data from all randomized participants who received at least 1 dose of study drug LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 5.566 units on a scale | Standard Deviation 9.168 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 5.725 units on a scale | Standard Deviation 8.706 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 6.057 units on a scale | Standard Deviation 13.512 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 8.924 units on a scale | Standard Deviation 9.469 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 7.250 units on a scale | Standard Deviation 9.245 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 5.838 units on a scale | Standard Deviation 7.946 |
| Placebo (TNFα-IR Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 4.953 units on a scale | Standard Deviation 9.152 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 4.400 units on a scale | Standard Deviation 8.068 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A | 6.627 units on a scale | Standard Deviation 8.401 |
p-value: 0.272ANCOVA
p-value: 0.962ANCOVA
p-value: 0.236ANCOVA
p-value: 0.316ANCOVA
p-value: 0.138ANCOVA
p-value: 0.975ANCOVA
p-value: 0.079ANCOVA
Secondary
Change From Baseline in HAQ-DI - Part A
HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range of 0 to 3. Negative mean changes from baseline indicated improvement.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.220 units on a scale | Standard Deviation 0.459 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.322 units on a scale | Standard Deviation 0.493 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.418 units on a scale | Standard Deviation 0.693 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.537 units on a scale | Standard Deviation 0.639 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.469 units on a scale | Standard Deviation 0.517 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part A | -0.476 units on a scale | Standard Deviation 0.655 |
| Placebo (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part A | -0.182 units on a scale | Standard Deviation 0.458 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part A | -0.223 units on a scale | Standard Deviation 0.448 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part A | -0.265 units on a scale | Standard Deviation 0.496 |
p-value: 0.538Fisher Exact
p-value: 0.515Fisher Exact
p-value: 0.03Fisher Exact
p-value: 0.053Fisher Exact
p-value: 0.393Fisher Exact
p-value: 0.077Fisher Exact
p-value: 0.105Fisher Exact
Secondary
Change From Baseline in HAQ-DI - Part B
HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 HAQ-DI results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.616 units on a scale | Standard Deviation 0.609 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.542 units on a scale | Standard Deviation 0.611 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.665 units on a scale | Standard Deviation 0.662 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.673 units on a scale | Standard Deviation 0.705 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.554 units on a scale | Standard Deviation 0.614 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in HAQ-DI - Part B | -0.697 units on a scale | Standard Deviation 0.571 |
| Placebo (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part B | -0.331 units on a scale | Standard Deviation 0.449 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part B | -0.250 units on a scale | Standard Deviation 0.46 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in HAQ-DI - Part B | -0.309 units on a scale | Standard Deviation 0.437 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A
CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -1.575 mg/L | Standard Deviation 22.336 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -6.079 mg/L | Standard Deviation 10.289 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -9.435 mg/L | Standard Deviation 23.148 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -7.999 mg/L | Standard Deviation 14.74 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -11.968 mg/L | Standard Deviation 19.792 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -13.575 mg/L | Standard Deviation 25.692 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | 1.229 mg/L | Standard Deviation 14.811 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -9.521 mg/L | Standard Deviation 20.312 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A | -8.297 mg/L | Standard Deviation 21.955 |
p-value: <0.001ANCOVA
p-value: 0.012ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B
CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 CRP results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -10.548 mg/L | Standard Deviation 18.555 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -4.556 mg/L | Standard Deviation 12.937 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -11.340 mg/L | Standard Deviation 23.347 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -7.865 mg/L | Standard Deviation 22.607 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -14.519 mg/L | Standard Deviation 19.26 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -6.860 mg/L | Standard Deviation 16.745 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -12.094 mg/L | Standard Deviation 28.917 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -10.130 mg/L | Standard Deviation 18.03 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B | -9.004 mg/L | Standard Deviation 19.698 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A
Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as no pain and the right end (100 mm) marked worst possible pain. The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -14.8 mm | Standard Deviation 23.7 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -18.7 mm | Standard Deviation 22.8 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -21.3 mm | Standard Deviation 28.4 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -29.8 mm | Standard Deviation 24.1 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -25.8 mm | Standard Deviation 23 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -25.3 mm | Standard Deviation 27.5 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -9.4 mm | Standard Deviation 24 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -10.3 mm | Standard Deviation 24.7 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A | -18.8 mm | Standard Deviation 26.6 |
p-value: 0.042ANCOVA
p-value: 0.055ANCOVA
p-value: 0.365ANCOVA
p-value: 0.005ANCOVA
p-value: 0.247ANCOVA
p-value: 0.315ANCOVA
p-value: 0.006ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B
Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as no pain and the right end (100 mm) marked worst possible pain. The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 PAAP-VAS results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -32.5 mm | Standard Deviation 27.8 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -26.2 mm | Standard Deviation 20.3 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -33.3 mm | Standard Deviation 33.4 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -36.2 mm | Standard Deviation 27.4 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -32.4 mm | Standard Deviation 22.6 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -41.2 mm | Standard Deviation 23 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -25.5 mm | Standard Deviation 22.3 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -16.5 mm | Standard Deviation 21.1 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B | -26.2 mm | Standard Deviation 26.2 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A
The investigator gave an overall assessment of the severity of the participants disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity and the right end (100 mm) marked as extremely active arthritis. A negative change indicated a lessening in the severity of the participant's disease activity.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -16.0 mm | Standard Deviation 19 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -21.0 mm | Standard Deviation 15.6 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -21.7 mm | Standard Deviation 25.2 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -26.7 mm | Standard Deviation 18.1 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -24.5 mm | Standard Deviation 22.3 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -28.8 mm | Standard Deviation 24.2 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -8.6 mm | Standard Deviation 21.4 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -25.7 mm | Standard Deviation 22.2 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A | -22.0 mm | Standard Deviation 24 |
p-value: 0.09ANCOVA
p-value: 0.131ANCOVA
p-value: 0.008ANCOVA
p-value: 0.013ANCOVA
p-value: 0.01ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B
The investigator gave an overall assessment of the severity of the participant's disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity and the right end (100 mm) marked as extremely active arthritis. A negative change indicated a lessening in the severity of the participant's disease activity.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 PhGA-VAS results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -36.1 mm | Standard Deviation 21.7 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -30.1 mm | Standard Deviation 22 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -38.5 mm | Standard Deviation 28.4 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -38.0 mm | Standard Deviation 18.5 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -31.0 mm | Standard Deviation 20.7 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -44.4 mm | Standard Deviation 17.7 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -30.1 mm | Standard Deviation 22.5 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -28.9 mm | Standard Deviation 25.8 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B | -32.7 mm | Standard Deviation 25.2 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A
The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity to the right end (100 mm) marked extremely active arthritis. A negative change indicated an improvement in the participant's assessment of disease activity.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -19.2 mm | Standard Deviation 21.4 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -17.3 mm | Standard Deviation 20.9 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -18.5 mm | Standard Deviation 28.7 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -29.1 mm | Standard Deviation 23.1 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -22.1 mm | Standard Deviation 23.7 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -30.1 mm | Standard Deviation 26.9 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -10.1 mm | Standard Deviation 24.7 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -12.1 mm | Standard Deviation 27.9 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A | -21.6 mm | Standard Deviation 25.4 |
p-value: 0.778ANCOVA
p-value: 0.865ANCOVA
p-value: 0.03ANCOVA
p-value: 0.331ANCOVA
p-value: 0.039ANCOVA
p-value: 0.292ANCOVA
p-value: 0.003ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B
The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as no arthritis activity to the right end (100 mm) marked extremely active arthritis. A negative change indicated an improvement in the participant's assessment of disease activity.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 PtGADA-VAS results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -35.4 mm | Standard Deviation 26.2 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -24.9 mm | Standard Deviation 25.4 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -31.8 mm | Standard Deviation 30.4 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -34.8 mm | Standard Deviation 27 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -28.5 mm | Standard Deviation 24.7 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -39.8 mm | Standard Deviation 25.5 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -22.4 mm | Standard Deviation 23.2 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -17.8 mm | Standard Deviation 21.4 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B | -25.1 mm | Standard Deviation 23.9 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A
SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints count ranged from 0-28. A negative change indicated fewer swollen joints.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -2.69 swollen joints | Standard Deviation 6.07 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -4.25 swollen joints | Standard Deviation 5.58 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -6.51 swollen joints | Standard Deviation 7.65 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -6.16 swollen joints | Standard Deviation 6.44 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -7.49 swollen joints | Standard Deviation 7.98 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -6.52 swollen joints | Standard Deviation 6.62 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -1.69 swollen joints | Standard Deviation 5.93 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -5.57 swollen joints | Standard Deviation 5.51 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A | -5.15 swollen joints | Standard Deviation 5.65 |
p-value: 0.001ANCOVA
p-value: 0.028ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.093ANCOVA
p-value: 0.023ANCOVA
p-value: 0.006ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B
SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints ranged from 0-28. A negative change indicated fewer swollen joints.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 SJC results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -7.25 swollen joints | Standard Deviation 6.15 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -5.73 swollen joints | Standard Deviation 4.95 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -9.06 swollen joints | Standard Deviation 5.92 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -7.26 swollen joints | Standard Deviation 5.73 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -8.95 swollen joints | Standard Deviation 6.64 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -8.96 swollen joints | Standard Deviation 6.06 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -7.32 swollen joints | Standard Deviation 6.45 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -5.46 swollen joints | Standard Deviation 6.51 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B | -6.29 swollen joints | Standard Deviation 5.75 |
Secondary
Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A
TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints.
Time frame: Baseline, up to Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -2.95 tender joints | Standard Deviation 5.2 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -6.02 tender joints | Standard Deviation 7.35 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -6.79 tender joints | Standard Deviation 7.67 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -7.05 tender joints | Standard Deviation 6.28 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -7.66 tender joints | Standard Deviation 8.96 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -8.96 tender joints | Standard Deviation 7.47 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -2.96 tender joints | Standard Deviation 6.31 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -6.02 tender joints | Standard Deviation 7.31 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A | -6.02 tender joints | Standard Deviation 6.74 |
p-value: 0.017ANCOVA
p-value: 0.042ANCOVA
p-value: 0.004ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.008ANCOVA
p-value: 0.007ANCOVA
Secondary
Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B
TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints.
Time frame: Baseline, Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 TJC results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -8.73 tender joints | Standard Deviation 6.85 |
| 3 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -8.78 tender joints | Standard Deviation 5.32 |
| 10 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -11.43 tender joints | Standard Deviation 6.54 |
| 30 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -9.55 tender joints | Standard Deviation 6.2 |
| 80 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -10.86 tender joints | Standard Deviation 7.48 |
| 180 mg LY2439821 (bDMARD-naive Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -10.55 tender joints | Standard Deviation 7.11 |
| Placebo (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -6.62 tender joints | Standard Deviation 8.39 |
| 80 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -7.35 tender joints | Standard Deviation 6.83 |
| 180 mg LY2439821 (TNFα-IR Population) | Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B | -6.81 tender joints | Standard Deviation 6.11 |
Secondary
Percentage of Participants in EULAR28 - Part B
Assessment of participant's RA by the EULAR that is based on the DAS28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) \* 100.
Time frame: Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 EULAR28 results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 90.2 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 81.8 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 82.1 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 83.9 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 84.1 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in EULAR28 - Part B | 88.5 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants in EULAR28 - Part B | 64.5 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants in EULAR28 - Part B | 73.2 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants in EULAR28 - Part B | 69.7 percentage of participants |
Secondary
Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A
Assessment of participant's rheumatoid arthritis (RA) by the EULAR that is based on the DAS 28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) \* 100.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug; LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 44.4 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 67.5 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 60.0 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 75.7 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 73.2 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 75.7 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 36.5 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 60.0 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A | 65.5 percentage of participants |
p-value: 0.013Fisher Exact
p-value: 0.076Fisher Exact
p-value: 0.002Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.002Fisher Exact
p-value: 0.006Fisher Exact
p-value: 0.001Fisher Exact
Secondary
Percentage of Participants With ACR20/50/70 Response - Part A
ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70%, respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 \[or ACR50 or ACR70\] responders per treatment arm) / (total number of participants per treatment arm) \* 100.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 35.2 percentage of participants |
| Placebo (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 9.3 percentage of participants |
| Placebo (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 1.9 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 5.0 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 45.0 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 17.5 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 14.3 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 42.9 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 28.6 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 13.5 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 70.3 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 29.7 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 50.9 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 26.3 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 7.0 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 54.1 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 27.0 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 13.5 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 7.8 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 23.4 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 3.1 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 20.0 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 40.0 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 3.1 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR20 | 39.0 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR50 | 16.9 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With ACR20/50/70 Response - Part A | ACR70 | 10.2 percentage of participants |
p-value: 0.227Fisher Exact
p-value: 0.306Fisher Exact
p-value: 0.001Fisher Exact
p-value: 0.07Fisher Exact
p-value: 0.058Fisher Exact
p-value: 0.033Fisher Exact
p-value: 0.047Fisher Exact
p-value: 0.191Fisher Exact
p-value: 0.019Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.017Fisher Exact
p-value: 0.026Fisher Exact
p-value: 0.039Fisher Exact
p-value: 0.102Fisher Exact
p-value: 0.388Fisher Exact
p-value: 0.033Fisher Exact
p-value: 0.039Fisher Exact
p-value: 0.199Fisher Exact
p-value: 0.039Fisher Exact
p-value: 0.696Fisher Exact
p-value: 0.112Fisher Exact
Secondary
Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population
ACR20 responders were participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) \* 100.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug and were TNFα-IR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population | 23.4 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population | 40.0 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population | 39.0 percentage of participants |
p-value: 0.033Fisher Exact
p-value: 0.047Fisher Exact
Secondary
Percentage of Participants With Anti-LY2439821 Antibodies
Treatment-emergent anti-LY2439821 antibody positive participants were defined as a titer change from baseline that was at least 2 dilutions (4-fold) increase. Participants must have had an assessment to be classified as treatment emergent antibody positive or negative.
Time frame: Week 16, Week 64
Population: Part A (Week 16) FAS: all randomized participants who received at least 1 dose of study drug with antibody testing performed; Part B (Week 64): All participants from Part A who entered the open-label portion of the study, part B, with baseline and at least 1 post-baseline antibody testing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 0.0 percentage of participants |
| Placebo (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 11.6 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 0.0 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 14.3 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 8.8 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 3.6 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 8.6 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 0.0 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 16.3 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 2.5 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 3.8 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 15.2 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 7.7 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 6.5 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 10.5 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 0.0 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part B Week 64 (n=37,32,28,30,40,26,31,41,33) | 9.1 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With Anti-LY2439821 Antibodies | Part A Week 16 (n=43,35,34,35,49,33,52,57,51) | 13.7 percentage of participants |
Secondary
Percentage of Participants With of ACR20/50/70 Response - Part B
ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70% respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 \[or ACR50 or ACR70\] responders per treatment arm) / (total number of participants per treatment arm) \* 100\].
Time frame: Week 64
Population: All participants from Part A who entered the open-label portion of the study, Part B, with Week 64 ACR20/50/70 results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 75.0 percentage of participants |
| Placebo (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 42.5 percentage of participants |
| Placebo (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 17.5 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 12.5 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 37.5 percentage of participants |
| 3 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 65.6 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 67.9 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 50.0 percentage of participants |
| 10 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 32.1 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 22.6 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 48.4 percentage of participants |
| 30 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 80.6 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 47.7 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 72.7 percentage of participants |
| 80 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 11.4 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 61.5 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 30.8 percentage of participants |
| 180 mg LY2439821 (bDMARD-naive Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 80.8 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 51.6 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 32.3 percentage of participants |
| Placebo (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 19.4 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 43.9 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 22.0 percentage of participants |
| 80 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 9.8 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR50 | 38.2 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR70 | 17.6 percentage of participants |
| 180 mg LY2439821 (TNFα-IR Population) | Percentage of Participants With of ACR20/50/70 Response - Part B | ACR20 | 64.7 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State
Evaluable PK concentrations from all time points, including data from placebo participants who elected active treatment in Part B, were combined and utilized in a population approach to determine the population median estimates and 90% confidence intervals at steady state. Day 0 and Week 6 postdose samples were collected as late as possible during the dosing visit (in other words, the postdose samples were collected at the end of their respective visits).
Time frame: Predose: Day 0, Day 1 or 2 or 3, Day 7, Weeks 6, 10, 16, 40 and 64 and Postdose: Day 0 and Week 6
Population: All randomized participants who received at least 1 dose of study drug in Part A and had estimable PK data, as well as, participants from Part A who entered the open-label portion of the study, Part B, and had estimable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 336 nanograms per milliliter (ng/mL) |
| 3 mg LY2439821 (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 1060 nanograms per milliliter (ng/mL) |
| 10 mg LY2439821 (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 3230 nanograms per milliliter (ng/mL) |
| 30 mg LY2439821 (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 7580 nanograms per milliliter (ng/mL) |
| 80 mg LY2439821 (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 17100 nanograms per milliliter (ng/mL) |
| 180 mg LY2439821 (bDMARD-naive Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 7320 nanograms per milliliter (ng/mL) |
| Placebo (TNFα-IR Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 16200 nanograms per milliliter (ng/mL) |
| 80 mg LY2439821 (TNFα-IR Population) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State | 18600 nanograms per milliliter (ng/mL) |
Secondary
Relationship Between Exposure and Response of ACR20/50/70/N
Time frame: Through Week 72
Population: Relationship between exposure and response ACR20/50/70/N analysis was reported in OMs 8 and 9, as percentage of participants with ACR 20/50/70 Response (Parts A and B) and OMs 24 and 25 as percentage of participants with ACR-N (Parts A and B) respectively. No further analyses were completed for ACR20/50/70/N.
Secondary
Relationship Between Exposure and Response of DAS28
Time frame: Through Week 72
Population: Relationship between exposure and response of DAS28 analysis was reported in OMs 6 and 7 as change from baseline in DAS28 (Parts A and B) respectively. No further analyses were completed for DAS28.
Secondary
Relationship Between Exposure and Response of EULAR28
Time frame: Through Week 72
Population: Relationship between exposure and response of EULAR 28 analysis was reported in OMs 22 and 23 as percentage of participants in EULAR28 (Parts A and B), respectively. No further analyses were completed for EULAR28.
Secondary
Relationship Between Exposure and Response of Individual Components of the ACR Core Set
Time frame: Through Week 72
Population: Relationship between exposure and response in Individual Components (IC) of ACR Core Set analysis was reported in outcome measures (OMs) 10-21 as change from baseline in IC of ACR Core Sets: TJC, SJC, PAAP-VAS, PtGADA-VAS, PhGA-VAS, and CRP (Parts A and B). No further analyses were completed for individual components of ACR Core Set.
Secondary
Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population
ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. The model used in the dose response analysis was used to estimate the doses that achieved 10%, 50%, and 90% of the maximal drug efficacy. Missing values were imputed using NRI. The log transformed dose was evaluated.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug and were bDMARD-naive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population | Estimated dose to achieve 10% response | 0.8 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population | Estimated dose to achieve 50% response | 2.4 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population | Estimated dose to achieve 90% response | 13.8 log (dose) mg |
Secondary
Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population
ACR50 responders were participants with at least 50% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug and were bDMARD-naive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population | Estimated dose to achieve 10% response | 7.3 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population | Estimated dose to achieve 50% response | 37.9 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population | Estimated dose to achieve 90% response | 81.2 log (dose) mg |
Secondary
Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population
DAS modified included the 28 diarthrodial joint count (DAS28) that consisted of a composite score of the following variables: TJC out of 28 (TJC28), SJC out of 28 (SJC28), CRP \[milligrams per liter (mg/L)\], and PtGADA on a 0 to 100 millimeter (mm) VAS ranging from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 was calculated as: DAS28 - CRP = 0.56(square root of TJC28) + 0.28(square root of SJC28) + 0.36(ln\[CRP +1\]) + 0.014(VAS) + 0.96.
Time frame: Week 12
Population: Part A FAS: All randomized participants who received at least 1 dose of study drug and were bDMARD-naive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population | Estimated dose to achieve 10% response | 7.3 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population | Estimated dose to achieve 50 % response | 41.5 log (dose) mg |
| Placebo (bDMARD-naive Population) | Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population | Estimated dose to achieve 90% response | 97.0 log (dose) mg |