Arthritis, Rheumatoid
Conditions
Keywords
Rheumatoid Arthritis, RA
Brief summary
The purpose of this trial is to evaluate the safety and efficacy of LY3009104 in participants with Rheumatoid Arthritis (RA).
Detailed description
This study consists of the following: * Screening period: 4 to 28-days * Part A: a 12-week blinded, placebo controlled treatment period * Part B: a 12-week blinded extension period * Part C: an optional 52-week open-label extension period * Part D: an additional optional 52-week open-label extension period * Follow up period: 28 days
Interventions
DRUGPlacebo
Administered orally
DRUGLY3009104
Administered orally
DRUGMethotrexate
Administered orally as background therapy
Sponsors
Incyte Corporation
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
* Must have active RA * Must regularly use methotrexate (MTX) for at least 12 weeks before your participation in this study * Must have American College of Rheumatology (ACR) functional class I, II, or III * Must have C-reactive protein (CRP) measurement \> 1.2 times upper limit of normal (ULN) or Erythrocyte Sedimentation Rate (ESR) \> ULN \[28 millimeters/hour (mm/hr)\] * Have laboratory values that in the opinion of the investigator do not pose an unacceptable risk to the participants if study drug would be administered * Must have venous access sufficient to allow blood sampling as per the protocol * Must be reliable and willing to be available for the duration of the study and are willing to follow study procedures * Must be able to read, understand, and give written informed consent approved by Lilly or its designee and the ethical review board (ERB) governing the site * Male participants: agree to use 2 forms of highly effective methods of birth control with female partners of childbearing potential during the study * If you are a woman and you could become pregnant during this study, you must talk to the study doctor about birth control. You are required to use 2 forms of highly effective methods of birth control 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 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 * For participants receiving corticosteroids, you must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to randomization * Continue to meet inclusion criteria for Parts A and B as applicable * Part D only: have completed the 52 weeks (Week 24 to Week 76) of participation in Part C of the study without permanent study drug discontinuation and have not completed the Follow-Up Visit (approximately 28 days after the last dose of study drug)
Exclusion criteria
* Must not have received any parenteral corticosteroid administered by intra-articular, intramuscular (IM), or intravenous (IV) injection within 6 weeks prior to baseline * Must not be concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 4 weeks * Must not have received any prior biologic disease modifying anti-rheumatic drug (DMARD) therapy \[such as Tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-6, T-cell or B-cell target therapies) * Must not have used DMARDs other than methotrexate (MTX), hydroxychloroquine, or sulfasalazine within the last 8 weeks * Must not have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body * Must not have previously been randomized, completed or withdrawn from this study or any other study investigating LY3009104 * Must not have received prior treatment with an oral JAK inhibitor * Must not have a current or recent (within the last 30 days) viral, bacterial, fungal, or parasitic infection * Must not have had a serious infection (for example, pneumonia, cellulitis, or bone or joint infections) or atypical mycobacterial infection within the last 6 months * Must not have had symptomatic herpes zoster or herpes simplex infection within the last 90 days or have a history of disseminated/complicated herpes zoster * Must not have evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies * Must not have evidence of hepatitis C virus (HCV) or active hepatitis B * Must not have evidence or suspicion of active or latent tuberculosis (TB) * Must not have another serious disorder or illness * Must not be exposed to a live vaccine within the last 12 weeks * Must not have donated more than 500 milliliters (mL) of blood within the last month * Must not have had surgery on a joint that is to be assessed in the study within the last 2 months, or will require such during the study * Must not be currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Presence of significant uncontrolled cerebro-cardiovascular \[for example (eg), myocardial infarction (MI), unstable angina (UA), unstable arterial hypertension, severe heart failure or cerebrovascular accident\], respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematologic or neuropsychiatric disorders, or abnormal laboratory values that in the opinion of the investigator pose an unacceptable risk to the participant if study drug would be administered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 | Baseline through Week 12 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Baseline through Weeks 2, 4, 8, 12, 16, 20, 24 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) \* 100. |
| Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Baseline through Weeks 76 and 128 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100. |
| Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Baseline through Weeks 2, 4, 8, 12, 16, 20, 24 | ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. |
| Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Baseline through Weeks 76 and 128 | ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. |
| Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Baseline through Weeks 2, 4, 8, 12, 16, 20, 24 | ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100. |
| Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Baseline through Weeks 76 and 128 | ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100. |
| Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | Baseline through Week 12 | ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval. |
| Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Baseline, Weeks 12 and 24 | ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation. |
| ACR Percent Improvement (ACR-N) | Baseline through Week 12 | ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval. |
| Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | Baseline, Weeks 12 and 24 | TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. |
| Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | Baseline, Weeks 76 and 128 | TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. |
| Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Baseline, Weeks 12 and 24 | The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. |
| Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Baseline, Weeks 76 and 128 | The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. |
| Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Baseline, Weeks 12 and 24 | hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation. |
| Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Baseline, Weeks 76 and 128 | hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation. |
| Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | Baseline through Week 12 | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval. |
| Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Baseline, Weeks 12 and 24 | Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain). |
| Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Baseline, Weeks 76 and 128 | Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain). |
| Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Baseline, Weeks 12 and 24 | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. |
| Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Baseline, Weeks 76 and 128 | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. |
| Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Baseline through Weeks 12 and 24 | EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units). |
| Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Baseline, Weeks 76 and 128 | EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units). |
| Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Baseline through Weeks 12 and 24 | Disease Activity Score (DAS) modified to include 28-joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders. |
| Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Baseline through Weeks 76 and 128 | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders. |
| Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Baseline, Weeks 4, 8, 12 | The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. |
| Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | Baseline, Week 12 | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains (physical functioning, bodily pain, role limitations due to physical problems and also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning. |
| Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | Baseline, Week 12 | The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 (No pain) to 10 (Pain as bad as you can imagine). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours. |
| Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | Baseline, Week 12 | The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (Not at all) to 4 (Very much) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. |
| Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | Baseline through 24 weeks | — |
| Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | Baseline through 24 weeks | — |
| Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0 | Baseline, 12 weeks | — |
| Mean Change From Baseline to Weeks 76 and 128 in ESR | Baseline, Weeks 76 and 128 | ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation. |
Countries
Croatia, Czechia, Hungary, India, Mexico, Poland, Romania, Ukraine, United States
Participant flow
Pre-assignment details
This study consisted of 4 parts and a follow-up up to 28 days post the last dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| 1 mg LY3009104 Administered orally QD for initial 12 weeks (Part A) followed by randomization to either 4 mg QD or 2 mg BID for an additional 12 weeks (Part B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.
MTX was administered orally as background therapy. | 49 |
| 2 mg LY3009104 Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.
MTX was administered orally as background therapy. | 52 |
| 4 mg LY3009104 Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.
MTX was administered orally as background therapy. | 52 |
| 8 mg LY3009104 Administered orally QD for 24 weeks (Parts A and B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment, participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.
MTX was administered orally as background therapy. | 50 |
| Placebo Placebo administered orally QD for initial 12 weeks (Part A) followed by randomization to either 4 mg QD or 2 mg BID for an additional 12 weeks (Part B). After 24 weeks of treatment, participants were eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally QD for 52 weeks. After 76 weeks of treatment participants were eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally QD for 52 additional weeks.
MTX was administered orally as background therapy. | 98 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (Weeks 0 Through 12) | Adverse Event | 1 | 1 | 1 | 1 | 5 | 0 | 0 | 0 | 0 | 0 |
| Part A (Weeks 0 Through 12) | Entry Criteria Not Met | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 |
| Part A (Weeks 0 Through 12) | Lack of Efficacy | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A (Weeks 0 Through 12) | Physician Decision | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Part A (Weeks 0 Through 12) | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part A (Weeks 0 Through 12) | Withdrawal by Subject | 2 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Part B (Weeks 12 Through 24) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part B (Weeks 12 Through 24) | Entry Criteria Not Met | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part B (Weeks 12 Through 24) | Lack of Efficacy | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (Weeks 12 Through 24) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part B (Weeks 12 Through 24) | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 | 3 | 4 | 0 | 0 | 0 |
| Part C (Weeks 24 Through 76) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 2 | 2 |
| Part C (Weeks 24 Through 76) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part C (Weeks 24 Through 76) | Entry Criteria Not Met | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part C (Weeks 24 Through 76) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Part C (Weeks 24 Through 76) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 |
| Part C (Weeks 24 Through 76) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part C (Weeks 24 Through 76) | Reason missing | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part C (Weeks 24 Through 76) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 2 | 2 |
| Part D (Weeks 76 Through 128) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Part D (Weeks 76 Through 128) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 |
| Part D (Weeks 76 Through 128) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | 2 mg LY3009104 | 1 mg LY3009104 | Placebo | Total | 8 mg LY3009104 | 4 mg LY3009104 |
|---|---|---|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 13.12 | 53.1 years STANDARD_DEVIATION 11.07 | 49.2 years STANDARD_DEVIATION 12.15 | 51.2 years STANDARD_DEVIATION 11.71 | 52.7 years STANDARD_DEVIATION 10.91 | 52.5 years STANDARD_DEVIATION 10.42 |
| Duration of Rheumatoid Arthritis | 5.53 years STANDARD_DEVIATION 4.377 | 5.45 years STANDARD_DEVIATION 3.885 | 5.40 years STANDARD_DEVIATION 4.283 | 5.62 years STANDARD_DEVIATION 4.401 | 6.63 years STANDARD_DEVIATION 5.048 | 5.28 years STANDARD_DEVIATION 4.466 |
| Erythrocyte Sedimentation Rate (ESR) | 36.5 millimeters/hour (mm/hr) STANDARD_DEVIATION 14.62 | 38.2 millimeters/hour (mm/hr) STANDARD_DEVIATION 17.57 | 39.9 millimeters/hour (mm/hr) STANDARD_DEVIATION 20.94 | 38.8 millimeters/hour (mm/hr) STANDARD_DEVIATION 18.39 | 43.3 millimeters/hour (mm/hr) STANDARD_DEVIATION 18.17 | 35.4 millimeters/hour (mm/hr) STANDARD_DEVIATION 17.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 10 Participants | 16 Participants | 56 Participants | 11 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 36 Participants | 78 Participants | 227 Participants | 36 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 4 Participants | 18 Participants | 3 Participants | 4 Participants |
| High Sensitivity C-Reactive Protein (hsCRP) | 12.02 milligrams/liter (mg/L) STANDARD_DEVIATION 22.111 | 11.22 milligrams/liter (mg/L) STANDARD_DEVIATION 12.41 | 14.03 milligrams/liter (mg/L) STANDARD_DEVIATION 23.527 | 12.81 milligrams/liter (mg/L) STANDARD_DEVIATION 19.402 | 14.32 milligrams/liter (mg/L) STANDARD_DEVIATION 15.602 | 11.39 milligrams/liter (mg/L) STANDARD_DEVIATION 16.941 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 7 Participants | 19 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 8 Participants | 15 Participants | 47 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 6 Participants | 11 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 40 Participants | 37 Participants | 70 Participants | 224 Participants | 37 Participants | 40 Participants |
| Region of Enrollment Croatia | 1 participants | 0 participants | 5 participants | 7 participants | 1 participants | 0 participants |
| Region of Enrollment Czech Republic | 3 participants | 4 participants | 7 participants | 23 participants | 3 participants | 6 participants |
| Region of Enrollment Hungary | 3 participants | 3 participants | 2 participants | 13 participants | 2 participants | 3 participants |
| Region of Enrollment India | 8 participants | 7 participants | 14 participants | 43 participants | 7 participants | 7 participants |
| Region of Enrollment Mexico | 8 participants | 7 participants | 16 participants | 47 participants | 8 participants | 8 participants |
| Region of Enrollment Poland | 5 participants | 4 participants | 11 participants | 33 participants | 7 participants | 6 participants |
| Region of Enrollment Romania | 2 participants | 2 participants | 3 participants | 11 participants | 3 participants | 1 participants |
| Region of Enrollment Ukraine | 6 participants | 6 participants | 9 participants | 29 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 16 participants | 16 participants | 31 participants | 95 participants | 16 participants | 16 participants |
| Sex: Female, Male Female | 44 Participants | 42 Participants | 85 Participants | 249 Participants | 41 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 13 Participants | 52 Participants | 9 Participants | 15 Participants |
| Swollen Joint Counts (SJC) | 17.0 number of joints STANDARD_DEVIATION 9.32 | 15.2 number of joints STANDARD_DEVIATION 6.55 | 15.8 number of joints STANDARD_DEVIATION 8.64 | 15.8 number of joints STANDARD_DEVIATION 8.13 | 16.1 number of joints STANDARD_DEVIATION 7.92 | 14.8 number of joints STANDARD_DEVIATION 7.54 |
| Tender Joint Counts (TJC) | 23.0 number of joints STANDARD_DEVIATION 12.6 | 21.4 number of joints STANDARD_DEVIATION 10.9 | 22.2 number of joints STANDARD_DEVIATION 12.06 | 22.2 number of joints STANDARD_DEVIATION 12.38 | 24.4 number of joints STANDARD_DEVIATION 13.76 | 19.9 number of joints STANDARD_DEVIATION 12.71 |
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 | 15 / 49 | 13 / 52 | 13 / 52 | 15 / 50 | 18 / 98 | 15 / 63 | 10 / 63 | 12 / 51 | 10 / 50 | 18 / 49 | 35 / 108 | 7 / 61 | 25 / 61 | 16 / 32 | 24 / 79 | 13 / 47 | 10 / 18 | 5 / 159 |
| serious Total, serious adverse events | 0 / 49 | 3 / 52 | 2 / 52 | 1 / 50 | 3 / 98 | 2 / 63 | 1 / 63 | 0 / 51 | 0 / 50 | 3 / 49 | 16 / 108 | 1 / 61 | 6 / 61 | 6 / 32 | 5 / 79 | 3 / 47 | 0 / 18 | 2 / 159 |
Outcome results
Primary
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Week 12
Population: All randomized participants who received placebo, 4 mg or 8 mg LY3009104 in Part A. Participants who had missing components of the ACR20 index at Week 12 had these components imputed by last observation carried forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 | 76 percentage of participants |
| Placebo | Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12 | 41 percentage of participants |
p-value: <0.001Regression, Logistic
Secondary
ACR Percent Improvement (ACR-N)
ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
Time frame: Baseline through Week 12
Population: All randomized participants who received study drug in Part A. Participants who had missing components of the ACR-N at Week 12 had these components imputed by LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 or 8 mg LY3009104 | ACR Percent Improvement (ACR-N) | 17.30 percentage of improvement |
| Placebo | ACR Percent Improvement (ACR-N) | 19.42 percentage of improvement |
| 4 mg LY3009104 | ACR Percent Improvement (ACR-N) | 28.59 percentage of improvement |
| 8 mg LY3009104 | ACR Percent Improvement (ACR-N) | 29.00 percentage of improvement |
| Placebo | ACR Percent Improvement (ACR-N) | 10.97 percentage of improvement |
Secondary
Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness
The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.
Time frame: Baseline, Weeks 4, 8, 12
Population: All randomized participants who received study drug in Part A and had morning stiffness evaluated at analysis time points. LOCF was used to impute missing post-baseline values for Week 12 analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 4 (n=47, 50, 50, 50, 94) | -34.1 minutes | Standard Deviation 70.49 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 12 (n=48, 51, 50, 50, 97) | -49.5 minutes | Standard Deviation 72.8 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 8 (n=46, 50, 50, 50, 86) | -41.2 minutes | Standard Deviation 85.45 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 8 (n=46, 50, 50, 50, 86) | -31.1 minutes | Standard Deviation 45.8 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 4 (n=47, 50, 50, 50, 94) | -27.0 minutes | Standard Deviation 46.49 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 12 (n=48, 51, 50, 50, 97) | -30.7 minutes | Standard Deviation 47.41 |
| 4 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 8 (n=46, 50, 50, 50, 86) | -67.8 minutes | Standard Deviation 138.02 |
| 4 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 4 (n=47, 50, 50, 50, 94) | -57.4 minutes | Standard Deviation 149 |
| 4 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 12 (n=48, 51, 50, 50, 97) | -75.0 minutes | Standard Deviation 142.04 |
| 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 4 (n=47, 50, 50, 50, 94) | -25.5 minutes | Standard Deviation 126.13 |
| 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 12 (n=48, 51, 50, 50, 97) | -62.7 minutes | Standard Deviation 88.27 |
| 8 mg LY3009104 | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 8 (n=46, 50, 50, 50, 86) | -53.8 minutes | Standard Deviation 101.76 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 8 (n=46, 50, 50, 50, 86) | -25.5 minutes | Standard Deviation 67.39 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 4 (n=47, 50, 50, 50, 94) | -22.5 minutes | Standard Deviation 63.61 |
| Placebo | Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness | Week 12 (n=48, 51, 50, 50, 97) | -33.9 minutes | Standard Deviation 91.79 |
p-value: 0.015ANCOVA
p-value: 0.073ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0
Time frame: Baseline, 12 weeks
Population: Zero participants were analyzed. Assessment of ENSEMBLE Minimum Data Set 1.0 was not collected at Week 12 and therefore results are not reported for outcome measure.
Secondary
Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score
The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 (No pain) to 10 (Pain as bad as you can imagine). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours.
Time frame: Baseline, Week 12
Population: All randomized participants who received study drug and had BPI-sf worst-pain-in-the past-24-hours item evaluated at Week 12. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | -1.35 units on a scale | Standard Deviation 2.547 |
| Placebo | Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | -0.67 units on a scale | Standard Deviation 2.132 |
| 4 mg LY3009104 | Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | -1.41 units on a scale | Standard Deviation 1.813 |
| 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | -1.54 units on a scale | Standard Deviation 2.131 |
| Placebo | Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score | -0.35 units on a scale | Standard Deviation 2.136 |
p-value: 0.005ANCOVA
p-value: 0.135ANCOVA
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score
The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (Not at all) to 4 (Very much) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.
Time frame: Baseline, Week 12
Population: All randomized participants who received study drug in Part A and had FACIT-F evaluated at Week 12. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | 4.48 units on a scale | Standard Deviation 10.492 |
| Placebo | Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | 3.80 units on a scale | Standard Deviation 9.152 |
| 4 mg LY3009104 | Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | 4.41 units on a scale | Standard Deviation 8.631 |
| 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | 4.11 units on a scale | Standard Deviation 9.971 |
| Placebo | Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score | 2.02 units on a scale | Standard Deviation 8.941 |
p-value: 0.203ANCOVA
p-value: 0.164ANCOVA
p-value: 0.018ANCOVA
p-value: 0.097ANCOVA
Secondary
Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains (physical functioning, bodily pain, role limitations due to physical problems and also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.
Time frame: Baseline, Week 12
Population: All randomized participants who received study drug in Part A and had SF-36 evaluated at analysis time point. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 6.66 units on a scale | Standard Deviation 8.074 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 2.54 units on a scale | Standard Deviation 11.983 |
| Placebo | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 4.15 units on a scale | Standard Deviation 7.68 |
| Placebo | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 1.89 units on a scale | Standard Deviation 6.869 |
| 4 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 7.07 units on a scale | Standard Deviation 7.378 |
| 4 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 2.39 units on a scale | Standard Deviation 7.898 |
| 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 3.03 units on a scale | Standard Deviation 10.675 |
| 8 mg LY3009104 | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 7.00 units on a scale | Standard Deviation 9.054 |
| Placebo | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 3.22 units on a scale | Standard Deviation 6.733 |
| Placebo | Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 0.88 units on a scale | Standard Deviation 10.437 |
p-value: 0.021ANCOVA
p-value: 0.194ANCOVA
p-value: <0.001ANCOVA
p-value: 0.012ANCOVA
p-value: 0.449ANCOVA
p-value: 0.578ANCOVA
p-value: 0.14ANCOVA
p-value: 0.266ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 24 | NA units on a scale | — |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 12 | -1.47 units on a scale | Standard Deviation 1.299 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 12 | -1.40 units on a scale | Standard Deviation 1.21 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 24 | -1.53 units on a scale | Standard Deviation 1.187 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 12 | -2.09 units on a scale | Standard Deviation 1.22 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 24 | -2.25 units on a scale | Standard Deviation 1.054 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 24 | -2.47 units on a scale | Standard Deviation 1.28 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 12 | -2.15 units on a scale | Standard Deviation 1.273 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 12 | -0.98 units on a scale | Standard Deviation 1.141 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP) | Week 24 | NA units on a scale | — |
p-value: 0.024ANCOVA
p-value: 0.03ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had ESR evaluated at analysis time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n=44, 51, 50, 49, 83) | -11.6 mm/hr | Standard Deviation 14.45 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n=0, 50, 48, 45, 0) | NA mm/hr | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n=44, 51, 50, 49, 83) | -6.4 mm/hr | Standard Deviation 16.81 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n=0, 50, 48, 45, 0) | -6.9 mm/hr | Standard Deviation 13.89 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n=44, 51, 50, 49, 83) | -11.5 mm/hr | Standard Deviation 17.28 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n=0, 50, 48, 45, 0) | -9.2 mm/hr | Standard Deviation 19 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n=0, 50, 48, 45, 0) | -13.7 mm/hr | Standard Deviation 21.62 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n=44, 51, 50, 49, 83) | -13.9 mm/hr | Standard Deviation 22.42 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 12 (n=44, 51, 50, 49, 83) | -6.0 mm/hr | Standard Deviation 19.49 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR) | Week 24 (n=0, 50, 48, 45, 0) | NA mm/hr | — |
p-value: 0.039ANCOVA
p-value: 0.458ANCOVA
p-value: 0.008ANCOVA
p-value: 0.029ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | NA units on a scale | — |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.35 units on a scale | Standard Deviation 0.528 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | -0.18 units on a scale | Standard Deviation 0.505 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.18 units on a scale | Standard Deviation 0.524 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.33 units on a scale | Standard Deviation 0.459 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | -0.32 units on a scale | Standard Deviation 0.506 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.39 units on a scale | Standard Deviation 0.497 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | -0.44 units on a scale | Standard Deviation 0.529 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 12 | -0.10 units on a scale | Standard Deviation 0.406 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Week 24 | NA units on a scale | — |
p-value: 0.003ANCOVA
p-value: 0.167ANCOVA
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)
hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 12 | -6.14 mg/L | Standard Deviation 10.236 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 24 | NA mg/L | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 12 | -3.39 mg/L | Standard Deviation 19.409 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 24 | -4.76 mg/L | Standard Deviation 18.695 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 12 | -7.06 mg/L | Standard Deviation 16.945 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 24 | -4.95 mg/L | Standard Deviation 19.819 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 24 | -7.61 mg/L | Standard Deviation 17.548 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 12 | -2.32 mg/L | Standard Deviation 32.582 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 12 | 1.50 mg/L | Standard Deviation 34.107 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP) | Week 24 | NA mg/L | — |
p-value: 0.016ANCOVA
p-value: 0.108ANCOVA
p-value: 0.008ANCOVA
p-value: 0.368ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain
Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had physician's and participant's assessments of disease activity and participant's pain evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 12 | -23.9 units on a scale | Standard Deviation 18.49 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 24 | NA units on a scale | — |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 12 | -24.9 units on a scale | Standard Deviation 27.26 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 24 | NA units on a scale | — |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 12 | -22.8 units on a scale | Standard Deviation 27.39 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 24 | NA units on a scale | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 12 | -14.2 units on a scale | Standard Deviation 17.82 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 24 | -14.7 units on a scale | Standard Deviation 20.57 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 12 | -25.0 units on a scale | Standard Deviation 20.81 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 12 | -16.2 units on a scale | Standard Deviation 22.43 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 24 | -16.9 units on a scale | Standard Deviation 24.96 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 24 | -27.8 units on a scale | Standard Deviation 21.13 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 24 | -30.2 units on a scale | Standard Deviation 21.85 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 12 | -25.0 units on a scale | Standard Deviation 19.22 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 12 | -30.4 units on a scale | Standard Deviation 18.75 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 12 | -25.4 units on a scale | Standard Deviation 21.61 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 24 | -35.5 units on a scale | Standard Deviation 17.72 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 24 | -27.3 units on a scale | Standard Deviation 22.11 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 24 | -30.0 units on a scale | Standard Deviation 20.9 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 24 | -37.8 units on a scale | Standard Deviation 18.73 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 12 | -29.8 units on a scale | Standard Deviation 21.2 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 24 | -26.9 units on a scale | Standard Deviation 19.22 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 12 | -25.3 units on a scale | Standard Deviation 20.31 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 12 | -33.5 units on a scale | Standard Deviation 19.49 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 12 | -8.8 units on a scale | Standard Deviation 22.77 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 12 | -10.3 units on a scale | Standard Deviation 22.02 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 24 | NA units on a scale | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of Pain - Week 24 | NA units on a scale | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient's Assessment of DA - Week 24 | NA units on a scale | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician's Assessment of DA - Week 12 | -19.0 units on a scale | Standard Deviation 21.4 |
p-value: 0.217ANCOVA
p-value: 0.092ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.072ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.082ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)
TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
Time frame: Baseline, Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 12 | -8.4 number of joints | Standard Deviation 12.7 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 24 | NA number of joints | — |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 12 | -8.1 number of joints | Standard Deviation 7.24 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 24 | NA number of joints | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 12 | -8.9 number of joints | Standard Deviation 9.03 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 12 | -11.3 number of joints | Standard Deviation 13.5 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 24 | -12.4 number of joints | Standard Deviation 12.6 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 24 | -10.0 number of joints | Standard Deviation 8.16 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 12 | -9.6 number of joints | Standard Deviation 6.49 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 12 | -12.2 number of joints | Standard Deviation 10.45 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 24 | -10.5 number of joints | Standard Deviation 6.42 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 24 | -14.0 number of joints | Standard Deviation 9.54 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 24 | -17.5 number of joints | Standard Deviation 11.23 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 12 | -14.7 number of joints | Standard Deviation 12.97 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 12 | -10.4 number of joints | Standard Deviation 8.88 |
| 8 mg LY3009104 | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 24 | -12.2 number of joints | Standard Deviation 7.29 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 12 | -6.7 number of joints | Standard Deviation 7.97 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 12 | -7.6 number of joints | Standard Deviation 12.31 |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | TJC - Week 24 | NA number of joints | — |
| Placebo | Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC) | SJC - Week 24 | NA number of joints | — |
p-value: 0.48ANCOVA
p-value: 0.064ANCOVA
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
p-value: 0.116ANCOVA
p-value: 0.201ANCOVA
p-value: <0.001ANCOVA
p-value: 0.002ANCOVA
Secondary
Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 76 (n=107, 61, 31) | -2.47 units on a scale | Standard Deviation 1.23 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 128 (n=79, 47, 18) | -2.56 units on a scale | Standard Deviation 1.16 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 76 (n=107, 61, 31) | -2.16 units on a scale | Standard Deviation 1.28 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 128 (n=79, 47, 18) | -2.02 units on a scale | Standard Deviation 1.23 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 76 (n=107, 61, 31) | -2.68 units on a scale | Standard Deviation 1.12 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP | Week 128 (n=79, 47, 18) | -2.35 units on a scale | Standard Deviation 1.4 |
Secondary
Mean Change From Baseline to Weeks 76 and 128 in ESR
ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had ESR evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 76 (n=108, 61, 32) | -13.0 mm/hr | Standard Deviation 18.84 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 128 (n=79, 47, 18) | -16.0 mm/hr | Standard Deviation 18.74 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 76 (n=108, 61, 32) | -7.4 mm/hr | Standard Deviation 26.28 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 128 (n=79, 47, 18) | -8.5 mm/hr | Standard Deviation 23.11 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 76 (n=108, 61, 32) | -8.9 mm/hr | Standard Deviation 23.12 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in ESR | Week 128 (n=79, 47, 18) | -15.5 mm/hr | Standard Deviation 23.07 |
Secondary
Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score
The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had HAQ-DI evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 76 (n=108, 61, 32) | -0.34 units on a scale | Standard Deviation 0.58 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 128 (n=79, 47, 18) | -0.31 units on a scale | Standard Deviation 0.61 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 76 (n=108, 61, 32) | -0.29 units on a scale | Standard Deviation 0.53 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 128 (n=79, 47, 18) | -0.22 units on a scale | Standard Deviation 0.56 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 76 (n=108, 61, 32) | -0.55 units on a scale | Standard Deviation 0.58 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score | Week 128 (n=79, 47, 18) | -0.30 units on a scale | Standard Deviation 0.66 |
Secondary
Mean Change From Baseline to Weeks 76 and 128 in hsCRP
hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had hsCRP evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 128 (n=79, 47, 18) | -6.8 mg/L | Standard Deviation 13.66 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 76 (n=108, 61, 32) | -3.9 mg/L | Standard Deviation 22.43 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 128 (n=79, 47, 18) | -2.9 mg/L | Standard Deviation 21.88 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 76 (n=108, 61, 32) | -3.3 mg/L | Standard Deviation 14.28 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 76 (n=108, 61, 32) | -2.9 mg/L | Standard Deviation 25.36 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in hsCRP | Week 128 (n=79, 47, 18) | -8.2 mg/L | Standard Deviation 12.33 |
Secondary
Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain
Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had physician's and participant's assessments of disease activity and pain evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 76 (n=108, 61, 32) | -40.3 units on a scale | Standard Deviation 19.15 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 128 (n=79, 47, 18) | -39.5 units on a scale | Standard Deviation 20.32 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 76 (n=108, 61, 32) | -27.5 units on a scale | Standard Deviation 26.49 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 128 (n=79, 47, 18) | -27.9 units on a scale | Standard Deviation 27.4 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 76 (n=108, 61, 32) | -25.1 units on a scale | Standard Deviation 24.1 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 128 (n=79, 47, 18) | -24.2 units on a scale | Standard Deviation 24.35 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 128 (n=79, 47, 18) | -18.0 units on a scale | Standard Deviation 28.85 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 76 (n=108, 61, 32) | -32.3 units on a scale | Standard Deviation 23.37 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 128 (n=79, 47, 18) | -19.3 units on a scale | Standard Deviation 29.72 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 76 (n=108, 61, 32) | -27.3 units on a scale | Standard Deviation 24.24 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 128 (n=79, 47, 18) | -31.0 units on a scale | Standard Deviation 25.54 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 76 (n=108, 61, 32) | -27.5 units on a scale | Standard Deviation 25.52 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 128 (n=79, 47, 18) | -34.0 units on a scale | Standard Deviation 27.51 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 76 (n=108, 61, 32) | -27.6 units on a scale | Standard Deviation 24.11 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 128 (n=79, 47, 18) | -22.3 units on a scale | Standard Deviation 22.99 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of DA-Week 128 (n=79, 47, 18) | -27.6 units on a scale | Standard Deviation 25.17 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Physician Assessment of DA-Week 76 (n=108, 61, 32) | -40.5 units on a scale | Standard Deviation 21.44 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain | Patient Assessment of Pain-Week 76 (n=108, 61, 32) | -23.4 units on a scale | Standard Deviation 23.49 |
Secondary
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC
TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had TJC and SJC evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 76 (n=108, 61, 32) | -15.7 units on a scale | Standard Deviation 11.26 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 128 (n=79, 47, 18) | -16.4 units on a scale | Standard Deviation 11.01 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 76 (n=108, 61, 32) | -11.6 units on a scale | Standard Deviation 6.4 |
| 4 or 8 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 128 (n=79, 47, 18) | -11.4 units on a scale | Standard Deviation 6.81 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 128 (n=79, 47, 18) | -12.4 units on a scale | Standard Deviation 8.01 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 76 (n=108, 61, 32) | -16.0 units on a scale | Standard Deviation 13.37 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 76 (n=108, 61, 32) | -12.9 units on a scale | Standard Deviation 7.8 |
| Placebo | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 128 (n=79, 47, 18) | -15.3 units on a scale | Standard Deviation 12.56 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 128 (n=79, 47, 18) | -11.6 units on a scale | Standard Deviation 6.23 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 128 (n=79, 47, 18) | -14.0 units on a scale | Standard Deviation 13.68 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | SJC - Week 76 (n=108, 61, 32) | -12.4 units on a scale | Standard Deviation 7.67 |
| 4 mg LY3009104 | Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC | TJC - Week 76 (n=108, 61, 32) | -18.1 units on a scale | Standard Deviation 12.06 |
Secondary
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24
Disease Activity Score (DAS) modified to include 28-joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.
Time frame: Baseline through Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had DAS28-CRP evaluated at analysis time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 12 | 22 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 12 | 14 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 24 | NA percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 24 | 31 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 12 | 23 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 12 | 15 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 24 | 15 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 24 | 33 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 24 | 50 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 12 | 48 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 12 | 37 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 12 | 40 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 12 | 22 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 24 | 46 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 24 | 36 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 12 | 4 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 12 | 19 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Remission - Week 24 | NA percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24 | Low Disease Activity - Week 24 | NA percentage of participants |
p-value: 0.409Fisher Exact
p-value: 0.371Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.007Fisher Exact
p-value: 0.033Fisher Exact
p-value: 0.019Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.001Fisher Exact
Secondary
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.
Time frame: Baseline through Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had DAS28-CRP evaluated at analysis time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 76 (n=108, 61, 32) | 58 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 76 (n=108, 61, 32) | 52 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 128 (n=79, 47, 18) | 59 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 128 (n=79, 47, 18) | 47 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 128 (n=79, 47, 18) | 26 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 76 (n=108, 61, 32) | 38 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 128 (n=79, 47, 18) | 36 percentage of participants |
| Placebo | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 76 (n=108, 61, 32) | 21 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 128 (n=79, 47, 18) | 39 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Remission - Week 76 (n=108, 61, 32) | 22 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 128 (n=79, 47, 18) | 56 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128 | Low Disease activity - Week 76 (n=108, 61, 32) | 44 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
Time frame: Baseline through Week 12
Population: All randomized participants who received study drug in Part A. Participants who had missing components of the ACR20 index at Week 12 had these components imputed by LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | 54.6 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | 55.2 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | 74.3 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | 77.2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response | 42.1 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) \* 100.
Time frame: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Population: All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 4 | 43 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 12 | 57 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 8 | 43 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 2 | 29 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 24 | 62 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 20 | 71 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 16 | 63 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 4 | 37 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 8 | 42 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 12 | 54 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 2 | 21 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 24 | 75 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 2 | 42 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 16 | 67 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 20 | 77 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 4 | 60 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 12 | 75 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 8 | 67 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 4 | 54 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 2 | 44 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 8 | 72 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 12 | 78 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 16 | 64 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 20 | 78 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 24 | 72 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 8 | 36 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 4 | 24 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 2 | 11 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24 | Week 12 | 41 percentage of participants |
p-value: 0.045Fisher Exact
p-value: 0.088Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Weeks 76 and 128
Population: All participants who received study drug in Parts C and D. Participants who had missing components of the ACR20 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 71 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 77 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 67 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 57 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 59 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 72 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Population: All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR50 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 4 | 10 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 2 | 0 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 8 | 16 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 12 | 31 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 8 | 10 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 24 | 19 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 2 | 4 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 20 | 27 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 16 | 19 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 12 | 17 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 4 | 10 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 20 | 46 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 12 | 35 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 2 | 21 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 8 | 33 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 4 | 29 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 16 | 38 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 24 | 46 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 2 | 4 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 4 | 22 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 8 | 36 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 12 | 40 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 16 | 44 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 20 | 48 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 24 | 54 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 8 | 7 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 4 | 3 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 2 | 2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24 | Week 12 | 10 percentage of participants |
p-value: 0.003Fisher Exact
p-value: 0.162Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
Time frame: Baseline through Week 12
Population: All randomized participants who received study drug in Part A. Participants who had missing components of the ACR50 index at analysis time point had these components imputed by LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | 26.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | 18.8 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | 34.4 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | 39.2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response | 12.0 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Weeks 76 and 128
Population: All participants who received study drug in Parts C and D. Participants who had missing components of the ACR50 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 49 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 58 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 41 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 30 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 44 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 44 percentage of participants |
Secondary
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24
ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Population: All randomized participants who received study drug in Parts A and B. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 2 | 0 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 8 | 4 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 4 | 2 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 12 | 12 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 16 | 8 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 12 | 8 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 4 | 4 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 2 | 2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 20 | 10 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 8 | 4 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 24 | 10 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 12 | 23 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 2 | 12 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 4 | 10 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 8 | 15 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 16 | 23 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 20 | 21 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 24 | 27 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 8 | 22 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 16 | 30 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 4 | 6 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 24 | 24 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 20 | 26 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 2 | 0 percentage of participants |
| 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 12 | 20 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 8 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 24 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 20 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 16 | NA percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 2 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24 | Week 12 | 2 percentage of participants |
p-value: 0.109Fisher Exact
p-value: 0.017Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128
ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.
Time frame: Baseline through Weeks 76 and 128
Population: All participants who received study drug in Parts C and D. Participants who had missing components of the ACR70 index at analysis time points had these components imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 29 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 28 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 18 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 17 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 76 (n=108, 61, 32) | 25 percentage of participants |
| 4 mg LY3009104 | Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128 | Week 128 (n=79, 47, 18) | 22 percentage of participants |
Secondary
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128
EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).
Time frame: Baseline, Weeks 76 and 128
Population: All participants who received study drug in Parts C and D and had EULAR28 evaluated at analysis time points. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 128 (n=79, 47, 18) | 30 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 76 (n=107, 61, 31) | 8 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 128 (n=79, 47, 18) | 5 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 76 (n=107, 61, 31) | 64 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 128 (n=79, 47, 18) | 65 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 76 (n=107, 61, 31) | 27 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 128 (n=79, 47, 18) | 40 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 128 (n=79, 47, 18) | 40 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 128 (n=79, 47, 18) | 19 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 76 (n=107, 61, 31) | 46 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 76 (n=107, 61, 31) | 41 percentage of participants |
| Placebo | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 76 (n=107, 61, 31) | 13 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 128 (n=79, 47, 18) | 17 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 128 (n=79, 47, 18) | 28 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 76 (n=107, 61, 31) | 55 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Moderate Response - Week 76 (n=107, 61, 31) | 39 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | No Response - Week 76 (n=107, 61, 31) | 6 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128 | Good Response - Week 128 (n=79, 47, 18) | 56 percentage of participants |
Secondary
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24
EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).
Time frame: Baseline through Weeks 12 and 24
Population: All randomized participants who received study drug in Parts A and B and had EULAR28 evaluated at analysis time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 12 | 35 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 12 | 43 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 24 | NA percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 12 | 22 percentage of participants |
| 4 or 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 24 | NA percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 12 | 17 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 24 | 23 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 12 | 63 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 12 | 19 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 24 | 25 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 24 | 52 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 24 | 15 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 24 | 42 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 24 | 42 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 12 | 23 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 12 | 31 percentage of participants |
| 4 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 12 | 46 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 12 | 46 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 12 | 40 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 24 | 22 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 12 | 14 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 24 | 46 percentage of participants |
| 8 mg LY3009104 | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 24 | 32 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 24 | NA percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 12 | 16 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 12 | 35 percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Good Response - Week 24 | NA percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | Moderate Response - Week 24 | NA percentage of participants |
| Placebo | Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24 | No Response - Week 12 | 49 percentage of participants |
p-value: 0.12Cochran-Mantel-Haenszel
p-value: 0.012Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104
Time frame: Baseline through 24 weeks
Population: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 36.5 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 36.1 |
| Placebo | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 59.1 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 21.3 |
| 4 mg LY3009104 | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 119.0 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 20.5 |
| 8 mg LY3009104 | Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104 | 241.0 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 22.9 |
Secondary
Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104
Time frame: Baseline through 24 weeks
Population: All randomized participants who received at least 1 dose of LY3009104 with evaluable LY3009104 PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 or 8 mg LY3009104 | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 333 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 61.7 |
| Placebo | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 541 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 38 |
| 4 mg LY3009104 | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 1060 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 37 |
| 8 mg LY3009104 | Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104 | 2190 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 45.6 |