A Study in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00966875
First received: August 25, 2009
Last updated: April 20, 2016
Last verified: April 2016
  Purpose

The primary purpose of the study is to help answer the following research questions, and not to provide treatment for Rheumatoid Arthritis (RA):

  • The safety of LY2439821 and any side effects that might be associated with it.
  • Whether LY2439821 can help participants with active RA.
  • How much LY2439821 should be given to participants.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: LY2439821
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Dose-Ranging Study of Multiple Subcutaneous Doses of LY2439821 (an Anti-IL-17 Antibody) in Patients With Active Rheumatoid Arthritis on Concomitant DMARD Therapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Dose-Response Relationship Measured by the Percentage of Participants With American College of Rheumatology (ACR) 20 Response in bDMARD-Naive Population [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR20 responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measured participants perceived degree of difficulty performing daily activities, C-reactive Protein (CRP), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), Patient's Global Assessment of Disease Activity-VAS(PtGADA-VAS), and Physician's Global Assessment of Disease Activity-VAS (PhGA-VAS). Missing values were imputed using Non-Responder Imputation (NRI). Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) * 100.


Secondary Outcome Measures:
  • Percentage of Participants With ACR20 Response in Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR) Population [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR20 responders were participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants achieving ACR20 response was calculated as: (number of ACR20 responders / number of participants treated) * 100.

  • Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR 20 Response in bDMARD-Naive Population [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR20 responders are participants with at least 20% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. The model used in the dose response analysis was used to estimate the doses that achieved 10%, 50%, and 90% of the maximal drug efficacy. Missing values were imputed using NRI. The log transformed dose was evaluated.

  • Smallest Doses That Achieved 10%, 50%, and 90% of the Maximum Disease Activity Score (DAS) 28 Response in bDMARD-Naive Population [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    DAS modified included the 28 diarthrodial joint count (DAS28) that consisted of a composite score of the following variables: TJC out of 28 (TJC28), SJC out of 28 (SJC28), CRP [milligrams per liter (mg/L)], and PtGADA on a 0 to 100 millimeter (mm) VAS ranging from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). DAS28 was calculated as: DAS28 − CRP = 0.56(square root of TJC28) + 0.28(square root of SJC28) + 0.36(ln[CRP +1]) + 0.014(VAS) + 0.96.

  • Smallest Doses That Achieve 10%, 50%, and 90% of the Maximum ACR50 Response in bDMARD-Naive Population [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR50 responders were participants with at least 50% improvement from baseline for TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI.

  • Change From Baseline in Disease Activity Score (DAS28)-Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 − CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln[CRP +1]) + 0.014(VAS) + 0.96. A negative change indicated an improvement.

  • Change From Baseline in DAS28 - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    DAS28 consisted of a composite score of the following variables: TJC28, SJC28, CRP, and PtGADA-VAS. DAS28 was calculated as: DAS28 − CRP =0.56(square root TJC28) + 0.28(square root SJC28) + 0.36(ln[CRP +1]) + 0.014(VAS) + 0.96. A negative change indicated an improvement.

  • Percentage of Participants With ACR20/50/70 Response - Part A [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70%, respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 [or ACR50 or ACR70] responders per treatment arm) / (total number of participants per treatment arm) * 100.

  • Percentage of Participants With of ACR20/50/70 Response - Part B [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    ACR20 (or ACR50 or ACR70) responders were participants with at least 20% (or 50% or 70% respectively) improvement from baseline TJC, SJC, and at least 3 of the 5 remaining core set measures: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. Missing values were imputed using NRI. Percentage of participants was calculated as: (number of ACR20 [or ACR50 or ACR70] responders per treatment arm) / (total number of participants per treatment arm) * 100].

  • Change From Baseline in Individual Components of the ACR Core Set-TJC - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints.

  • Change From Baseline in Individual Components of the ACR Core Set-TJC - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    TJC was determined by examination of 28 joint counts that were assessed for tenderness by pressure and joint manipulation on physical examination. The participant was asked for pain sensations on these manipulations and was watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-non-tender dichotomy. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, arthrodesed joints were identified by the investigator and excluded from evaluation during the study. Any joints that required intra-articular injections during the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of tender joints ranged from 0-28. A negative change indicated fewer tender joints.

  • Change From Baseline in Individual Components of the ACR Core Set-SJC - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints count ranged from 0-28. A negative change indicated fewer swollen joints.

  • Change From Baseline in Individual Components of the ACR Core Set-SJC - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    SJC was determined by examination of 28 joint that were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. Swelling secondary to osteoarthrosis was assessed as not swollen, unless there was unmistakable fluctuation. Joint assessments for each participant were performed by the same assessor, when possible, throughout the study to minimize variation. Replaced, ankylosed, or arthrodesed joints were identified by the investigator and were excluded from evaluation during the study. Any joints that required intra-articular injections over the course of the study were excluded from evaluation from the time of the injection to the conclusion of the study. The number of swollen joints ranged from 0-28. A negative change indicated fewer swollen joints.

  • Change From Baseline in Individual Components of the ACR Core Set-PAAP VAS - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as "no pain" and the right end (100 mm) marked "worst possible pain." The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain.

  • Change From Baseline in Individual Components of the ACR Core Set-PAAP-VAS - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    Participants were asked to assess his/her current level of arthritis pain by marking a vertical tick on a 100-mm horizontal VAS with the left end (0 mm) marked as "no pain" and the right end (100 mm) marked "worst possible pain". The scale was administered prior to the TJC and SJC count examinations. Results were expressed in mm measured between the left end of the scale and the crossing point of the vertical line of the tick. A negative change indicated a lessening of the participant's arthritis pain.

  • Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as "no arthritis activity" to the right end (100 mm) marked "extremely active arthritis." A negative change indicated an improvement in the participant's assessment of disease activity.

  • Change From Baseline in Individual Components of the ACR Core Set - PtGADA-VAS - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    The participant was asked to give an overall assessment of his/her current arthritis disease activity. The participants response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as "no arthritis activity" to the right end (100 mm) marked "extremely active arthritis." A negative change indicated an improvement in the participant's assessment of disease activity.

  • Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    The investigator gave an overall assessment of the severity of the participants disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as "no arthritis activity" and the right end (100 mm) marked as "extremely active arthritis." A negative change indicated a lessening in the severity of the participant's disease activity.

  • Change From Baseline in Individual Components of the ACR Core Set - PhGA-VAS - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    The investigator gave an overall assessment of the severity of the participant's disease activity. The physician's response was recorded by marking a vertical tick on a 100-mm VAS with the left end (0 mm) marked as "no arthritis activity" and the right end (100 mm) marked as "extremely active arthritis." A negative change indicated a lessening in the severity of the participant's disease activity.

  • Change From Baseline in Individual Components of the ACR Core Set - CRP - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity.

  • Change From Baseline in Individual Components of the ACR Core Set - CRP - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    CRP is a biological marker of disease activity. A negative change indicated an improvement in participant's disease activity.

  • Percentage of Participants in European League Against Rheumatism Responder Index (EULAR) 28 - Part A [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Assessment of participant's rheumatoid arthritis (RA) by the EULAR that is based on the DAS 28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) * 100.

  • Percentage of Participants in EULAR28 - Part B [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Assessment of participant's RA by the EULAR that is based on the DAS28 joint count. Participants were categorized as non-responders or responders (moderate responders + good responders). Percentage of participants was calculated as: (number of responders / number of participants) * 100.

  • ACR-N - Part A [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: [(post baseline value - baseline value) / baseline value] * 100.

  • ACR-N - Part B [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    ACR-N was a continuous measure of clinical, laboratory and functional outcomes in RA that characterized the percentage of improvement in RA disease activity from baseline. The index was defined as the lowest of either: the percent change in TJC, the percent change in SJC, or the median percent change of the remaining 5 ACR core criteria: HAQ-DI, CRP, PAAP-VAS, PtGADA-VAS, and PhGA-VAS. For each criterion, percent change was calculated as: [(post baseline value - baseline value)/baseline value] * 100.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    The FACIT Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue.

  • Change From Baseline in FACIT Fatigue Scale - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue Scale was a brief participant-reported questionnaire measure of fatigue and consisted of 13 items that assessed tiredness, weakness and difficulty conducting usual activities due to fatigue. Each question was scored on a 5-point scale from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. For missing data, scores were prorated using the average of the other answers in the scales as long as more than 50% of the items were answered. A negative change indicated less fatigue.

  • Change From Baseline in Duration of Morning Stiffness (Minutes) - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement.

  • Change From Baseline in Duration of Morning Stiffness (Minutes) - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    The investigator queried the participants about the duration of morning stiffness in and around their joints and the results (in minutes) were recorded by the investigator. Duration was the time from when the participants woke up to when normal activities could be resumed. Durations recorded as longer than 12 hours (720 minutes) were summarized as 720 minutes. An increase in duration from baseline indicated a joint worsening and a decrease from baseline indicated joint improvement.

  • Change From Baseline in HAQ-DI - Part A [ Time Frame: Baseline, up to Week 12 ] [ Designated as safety issue: No ]
    HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range of 0 to 3. Negative mean changes from baseline indicated improvement.

  • Change From Baseline in HAQ-DI - Part B [ Time Frame: Baseline, Week 64 ] [ Designated as safety issue: No ]
    HAQ-DI was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ-DI score. If the participant had scores for fewer than 6 categories, the HAQ-DI score was considered missing. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement.

  • Relationship Between Exposure and Response of Individual Components of the ACR Core Set [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
  • Relationship Between Exposure and Response of ACR20/50/70/N [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
  • Relationship Between Exposure and Response of DAS28 [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
  • Relationship Between Exposure and Response of EULAR28 [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2439821 at Steady State [ Time Frame: Predose: Day 0, Day 1 or 2 or 3, Day 7, Weeks 6, 10, 16, 40 and 64 and Postdose: Day 0 and Week 6 ] [ Designated as safety issue: No ]
    Evaluable PK concentrations from all time points, including data from placebo participants who elected active treatment in Part B, were combined and utilized in a population approach to determine the population median estimates and 90% confidence intervals at steady state. Day 0 and Week 6 postdose samples were collected as late as possible during the dosing visit (in other words, the postdose samples were collected at the end of their respective visits).

  • Percentage of Participants With Anti-LY2439821 Antibodies [ Time Frame: Week 16, Week 64 ] [ Designated as safety issue: Yes ]
    Treatment-emergent anti-LY2439821 antibody positive participants were defined as a titer change from baseline that was at least 2 dilutions (4-fold) increase. Participants must have had an assessment to be classified as treatment emergent antibody positive or negative.


Enrollment: 448
Study Start Date: August 2009
Study Completion Date: June 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3 mg LY2439821 (bDMARD-naive population)
3 milligrams (mg) LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. [Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD)]
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 10 mg LY2439821 (bDMARD-naive population)
10 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 30 mg LY2439821 (bDMARD-naive population)
30 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 80 mg LY2439821 (bDMARD-naive population)
80 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 180 mg LY2439821 (bDMARD-naive population)
180 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 80 mg LY2439821 (TNFa-IR population)
80 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60. [Tumor Necrosis Factor Alpha-Inadequate Responder (TNFα-IR)]
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Experimental: 180 mg LY2439821 (TNFa-IR population)
180 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Biological: LY2439821
Subcutaneous
Other Name: ixekizumab
Placebo Comparator: Placebo (bDMARD-naive population)
Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Drug: Placebo
Subcutaneous
Placebo Comparator: Placebo (TNFa-IR population)
Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160 mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.
Drug: Placebo
Subcutaneous

Detailed Description:
Study I1F-MC-RHAK is a multicenter study in participants with active RA on concomitant conventional DMARD therapy. The study is a Phase 2 study with 2 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design and Part B is an optional, open-label extension design. Two participant populations will be evaluated in this study: bDMARD-naive participants and TNFα-IR participants. Participants in Part A receive multiple subcutaneous injections of LY2439821 [bDMARD-naive participants: 0 (placebo), 3, 10, 30, 80, or 180 mg; TNFα-IR participants: 0 (placebo), 80 or 180 mg] at Weeks 0, 1, 2, 4, 6, 8, and 10. Participants in Part B receive subcutaneous injections of LY2439821 160 mg at Weeks 16, 18, and 20, and every 4 weeks thereafter through Week 60. Participants who complete both Part A and B have a total study participation of up to approximately 72 to 84 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • You must be between the ages of 18 and 75
  • You must have active RA

Qualifications Specific to the bDMARD-naive Population:

You must be regularly using methotrexate (MTX) for at least 12 weeks before your participation in this study

Qualifications Specific to the TNFα-IR Population:

  • You must have been treated with at least 1 biologic TNFα inhibitor therapy and either had an insufficient response to at least 3 months of treatment OR have been intolerant of such treatment
  • You must be regularly using at least 1 conventional DMARD in a stable treatment regimen

Exclusion Criteria:

  • You are concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 2 weeks
  • You are a woman who is lactating or breast feeding
  • You have donated more than 300 milliliters (mL) of blood within the last month
  • You have received glucocorticoid administered by intra-articular, intramuscular, or intravenous injection or oral corticosteroids at an average daily dose of greater than 10 mg per day of prednisone or its equivalent within the last 4 weeks
  • You had surgery on a joint that is to be assessed in the study within 2 months of study enrollment, or will require such during the study
  • You have another serious disorder or illness
  • You suffered a serious bacterial infection (for example, pneumonia, cellulitis, or bone or joint infections) within the last 3 months
  • You have a history of uncontrolled high blood pressure
  • You have clinical laboratory test results at entry that are outside the normal reference range
  • You are an employee of the clinic or you are an immediate family member of an employee of the clinic. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
  • You are currently participating in or were discontinued within the last 30 days from another clinical trial involving an investigational drug
  • If you are a woman and you could become pregnant during this study, you must talk to the study doctor about the birth control that you will use to avoid getting pregnant during the study.
  • If you are a post-menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months
  • If you are a post-menopausal woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test to see if you can participate.
  • If you are male, you must agree to reduce the risk of your female partner becoming pregnant during the study.

Exclusions Specific to the bDMARD-naive Population:

  • You have received any prior bDMARD therapy such as TNFα, Interleukin (IL)-1, IL-6, T-cell, or B-cell targeted therapies
  • You have had an inadequate response to a minimum of 3 months of treatment with 5 or more conventional DMARDs [such as leflunomide, azathioprine, cyclosporine, etcetera (etc.)]
  • You have used DMARDs other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
  • You have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body.

Exclusions Specific to the TNFα-IR Population:

  • You are currently using or recently used a bDMARD or a biologic TNFα inhibitor therapy within specified periods
  • You have had a serious reaction to other biologic DMARDs that, in the study doctor's opinion, puts you at serious risk
  • You have used cyclosporine or any other immunosuppressive in the 8 weeks before your participation in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966875

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Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT-5 hours, EST) Eli Lilly and Company
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00966875     History of Changes
Other Study ID Numbers: 12061  I1F-MC-RHAK 
Study First Received: August 25, 2009
Results First Received: April 20, 2016
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
rheumatoid arthritis
RA

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2016