Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
The primary purpose of this study is to help answer if LY2127399 is safe and effective during long-term treatment in participants with Rheumatoid Arthritis. This study is comprised of 2 periods: Period 1: Unblinded treatment for up to 240 weeks for participants who enroll from Study H9B-MC-BCDO (BCDO) (NCT01202760) or Study H9B-MC-BCDV (BCDV) (NCT01202773) or up to 168 weeks for participants who enroll from Study H9B-MC-BCDM (BCDM) (NCT01198002). Period 2: 48-week post-treatment follow-up
Detailed description
Week 16 non-responders (NR) are participants with \<20% improvement from baseline in both tender and swollen joint counts when assessed at Week 16 of Studies BCDO, BCDV and BCDM.
Interventions
DRUGLY2127399
Administered Subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have completed 24 weeks of participation in Study H9B-MC-BCDO or Study H9B-MC-BCDV, or have completed 100 weeks of participation in Study H9B-MC-BCDM * Woman must not be pregnant, breastfeeding, or become pregnant during the study
Exclusion criteria
* Current presence of a serious disorder or illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Immunoglobulin (Ig) Levels | Baseline, Week 48 | Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. |
| Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | up to 84.4 weeks during treatment period | A TEAE was defined as an event that first occurred or worsened in severity on or after the date of the first injection and prior to study termination. AESI are infection, injection site reactions, malignancy, major adverse cardiovascular events (MACE), allergy and hypersensitivity, depression, suicide/self-injury and pregnancy. MACE were defined as 1 of the adjudicated events: cardiovascular death, Myocardial infarction (MI), stroke, hospitalization for unstable angina, hospitalization for heart failure, coronary revascularization procedure, peripheral revascularization procedure, cardiogenic shock due to MI, resuscitated sudden death, serious arrhythmia, hospitalization for hypertension, peripheral arterial event. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Percentage of Participants Developing Anti-LY2127399 Antibodies | Baseline through Weeks 4, 24, 48 and 72 | Participants with treatment-emergent anti-LY2127399 antibodies were participants who had any samples from baseline up to and through Week 72 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants with anti-LY2127399 antibodies=(number of participants with treatment-emergent anti-LY2127399 antibodies / number of participants assessed)\*100. |
| Change From Baseline in Absolute B Cell Counts | Baseline, Week 48 | Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B cell count is the average of the values on or prior to the date of first injection of study treatment in preceding studies, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively, in B cell count. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores | Baseline, 240 weeks | — |
| Change From Baseline in Tender Joint Count (68 Joint Count) | Baseline, 240 weeks | — |
| Change From Baseline in Swollen Joint Count (66 Joint Count) | Baseline, 240 weeks | — |
| Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)] | Baseline, 240 weeks | — |
| Change From Baseline in Physicians Global Assessment of Disease Activity (VAS) | Baseline, 240 weeks | — |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline, 240 weeks | — |
| Change From Baseline in CRP | Baseline, 240 weeks | — |
| American College of Rheumatology Percent Improvement (ACR-N) | Baseline through 240 weeks | — |
| Change From Baseline in Participants Global Assessment of Disease Activity (VAS) | Baseline, 240 weeks | — |
| Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Baseline through Weeks 12, 24 and 48 | ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants achieving ACR20 response=(number of ACR20 responders / number of participants treated) \* 100. All participants who discontinue study treatment for any reason were defined as NR at that time point and going forward. |
| Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) | Baseline, 240 weeks | — |
| Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR-28) Response | Baseline through 240 weeks | — |
Other
| Measure | Time frame |
|---|---|
| Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period | Up to 84.4 weeks during treatment period and discontinuation from study treatment up to 48 weeks during follow-up period |
Countries
Argentina, Australia, Brazil, Bulgaria, Colombia, Croatia, France, Germany, Greece, Hungary, India, Japan, Lithuania, Malaysia, Mexico, New Zealand, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sri Lanka, Taiwan, Ukraine, United States
Participant flow
Pre-assignment details
Study consisted of a Treatment Period of up to 240 weeks for participants (pts) who enrolled from Studies H9B-MC-BCDO (BCDO) (NCT01202760) and H9B-MC-BCDV (BCDV) (NCT01202773) or up to 168 weeks for pts who enrolled from Study H9-MC-BCDM (BCDM) (NCT01198002). Discontinued pts were followed in Post-Treatment Follow-Up Period for up to 48 weeks.
Participants by arm
| Arm | Count |
|---|---|
| 120 mg LY2127399 (LY A) 120 mg LY2127399 administered SC Q4W.
Participants from Studies BCDO, BCDV and BCDM who were on 120 mg LY2127399 SC Q4W immediately prior to Study BCDP enrollment remained on 120 mg LY2127399 SC Q4W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 240 mg LY2127399 SC, 4 weeks later followed by 120 mg LY2127399 SC Q4W for the subsequent treatment. | 414 |
| 90 mg LY2127399 (LY B) 90 mg LY2127399 administered SC Q2W.
Participants from Studies BCDO, BCDV and BCDM who were on 90 mg LY2127399 SC Q2W immediately prior to Study BCDP enrollment remained on 90 mg LY2127399 SC Q2W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 180 mg LY2127399 SC, 2 weeks later followed by 90 mg LY2127399 SC Q2W for the subsequent treatment. | 672 |
| Total | 1,086 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post-Treatment Follow-Up Period | Death | 0 | 1 |
| Post-Treatment Follow-Up Period | Lost to Follow-up | 13 | 13 |
| Post-Treatment Follow-Up Period | Physician Decision | 1 | 2 |
| Post-Treatment Follow-Up Period | Sponsor Decision | 28 | 61 |
| Post-Treatment Follow-Up Period | Withdrawal by Subject | 43 | 69 |
| Treatment Period | Adverse Event | 15 | 26 |
| Treatment Period | Death | 2 | 4 |
| Treatment Period | Lack of Efficacy | 23 | 62 |
| Treatment Period | Lost to Follow-up | 3 | 4 |
| Treatment Period | Physician Decision | 5 | 5 |
| Treatment Period | Protocol Violation | 0 | 1 |
| Treatment Period | Sponsor Decision | 349 | 530 |
| Treatment Period | Withdrawal by Subject | 17 | 40 |
Baseline characteristics
| Characteristic | 120 mg LY2127399 (LY A) | Total | 90 mg LY2127399 (LY B) |
|---|---|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 10.9 | 52.6 years STANDARD_DEVIATION 11.4 | 52.4 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 152 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 218 Participants | 583 Participants | 365 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 144 Participants | 351 Participants | 207 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants | 53 Participants | 36 Participants |
| Race (NIH/OMB) Asian | 82 Participants | 207 Participants | 125 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 67 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 18 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 285 Participants | 735 Participants | 450 Participants |
| Region of Enrollment Argentina | 9 Participants | 23 Participants | 14 Participants |
| Region of Enrollment Australia | 1 Participants | 10 Participants | 9 Participants |
| Region of Enrollment Brazil | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Bulgaria | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment Colombia | 13 Participants | 35 Participants | 22 Participants |
| Region of Enrollment Croatia | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Germany | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Greece | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Hungary | 4 Participants | 14 Participants | 10 Participants |
| Region of Enrollment India | 13 Participants | 20 Participants | 7 Participants |
| Region of Enrollment Japan | 44 Participants | 116 Participants | 72 Participants |
| Region of Enrollment Lithuania | 16 Participants | 31 Participants | 15 Participants |
| Region of Enrollment Malaysia | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Mexico | 18 Participants | 43 Participants | 25 Participants |
| Region of Enrollment New Zealand | 7 Participants | 18 Participants | 11 Participants |
| Region of Enrollment Poland | 42 Participants | 78 Participants | 36 Participants |
| Region of Enrollment Romania | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Russia | 12 Participants | 33 Participants | 21 Participants |
| Region of Enrollment Slovakia | 9 Participants | 12 Participants | 3 Participants |
| Region of Enrollment South Africa | 23 Participants | 82 Participants | 59 Participants |
| Region of Enrollment South Korea | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment Sri Lanka | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment Taiwan | 7 Participants | 20 Participants | 13 Participants |
| Region of Enrollment Ukraine | 12 Participants | 33 Participants | 21 Participants |
| Region of Enrollment United States | 148 Participants | 442 Participants | 294 Participants |
| Sex: Female, Male Female | 339 Participants | 877 Participants | 538 Participants |
| Sex: Female, Male Male | 75 Participants | 209 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 130 / 414 | 251 / 672 | 47 / 368 | 71 / 591 |
| serious Total, serious adverse events | 30 / 414 | 57 / 672 | 15 / 368 | 28 / 591 |
Outcome results
Primary
Change From Baseline in Absolute B Cell Counts
Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B cell count is the average of the values on or prior to the date of first injection of study treatment in preceding studies, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively, in B cell count.
Time frame: Baseline, Week 48
Population: All participants from Studies BCDO and BCDV with an evaluable CD3-CD20+ B cell counts. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 120 mg LY2127399 (LY A) | Change From Baseline in Absolute B Cell Counts | -111.68 cells/microliter (cells/µL) | Standard Deviation 155.59 |
| 90 mg LY2127399 (LY B) | Change From Baseline in Absolute B Cell Counts | -121.30 cells/microliter (cells/µL) | Standard Deviation 132.68 |
| NR LY A to LY B | Change From Baseline in Absolute B Cell Counts | -134.68 cells/microliter (cells/µL) | Standard Deviation 130.21 |
| NR LY B to LY B | Change From Baseline in Absolute B Cell Counts | -110.92 cells/microliter (cells/µL) | Standard Deviation 125.3 |
| NR Placebo to LY B | Change From Baseline in Absolute B Cell Counts | -99.67 cells/microliter (cells/µL) | Standard Deviation 126.55 |
| Placebo to LY A | Change From Baseline in Absolute B Cell Counts | -75.92 cells/microliter (cells/µL) | Standard Deviation 142.78 |
| Placebo to LY B | Change From Baseline in Absolute B Cell Counts | -104.67 cells/microliter (cells/µL) | Standard Deviation 143.24 |
Primary
Change From Baseline in Serum Immunoglobulin (Ig) Levels
Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP.
Time frame: Baseline, Week 48
Population: All participants from Studies BCDO and BCDV with an evaluable serum Ig data. LOCF was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 120 mg LY2127399 (LY A) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.346 grams/liter (g/L) | Standard Deviation 0.372 |
| 120 mg LY2127399 (LY A) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.465 grams/liter (g/L) | Standard Deviation 2.112 |
| 120 mg LY2127399 (LY A) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.402 grams/liter (g/L) | Standard Deviation 0.58 |
| 90 mg LY2127399 (LY B) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.366 grams/liter (g/L) | Standard Deviation 2.166 |
| 90 mg LY2127399 (LY B) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.424 grams/liter (g/L) | Standard Deviation 0.604 |
| 90 mg LY2127399 (LY B) | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.332 grams/liter (g/L) | Standard Deviation 0.465 |
| NR LY A to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.422 grams/liter (g/L) | Standard Deviation 0.505 |
| NR LY A to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.499 grams/liter (g/L) | Standard Deviation 0.681 |
| NR LY A to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.321 grams/liter (g/L) | Standard Deviation 2.071 |
| NR LY B to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.196 grams/liter (g/L) | Standard Deviation 2.276 |
| NR LY B to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.465 grams/liter (g/L) | Standard Deviation 0.501 |
| NR LY B to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.387 grams/liter (g/L) | Standard Deviation 0.267 |
| NR Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.420 grams/liter (g/L) | Standard Deviation 1.651 |
| NR Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.298 grams/liter (g/L) | Standard Deviation 0.376 |
| NR Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.287 grams/liter (g/L) | Standard Deviation 0.228 |
| Placebo to LY A | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.300 grams/liter (g/L) | Standard Deviation 0.59 |
| Placebo to LY A | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.256 grams/liter (g/L) | Standard Deviation 0.289 |
| Placebo to LY A | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.376 grams/liter (g/L) | Standard Deviation 2.295 |
| Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgM | -0.267 grams/liter (g/L) | Standard Deviation 0.298 |
| Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgG | -1.415 grams/liter (g/L) | Standard Deviation 2.163 |
| Placebo to LY B | Change From Baseline in Serum Immunoglobulin (Ig) Levels | IgA | -0.407 grams/liter (g/L) | Standard Deviation 0.481 |
Primary
Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period
A TEAE was defined as an event that first occurred or worsened in severity on or after the date of the first injection and prior to study termination. AESI are infection, injection site reactions, malignancy, major adverse cardiovascular events (MACE), allergy and hypersensitivity, depression, suicide/self-injury and pregnancy. MACE were defined as 1 of the adjudicated events: cardiovascular death, Myocardial infarction (MI), stroke, hospitalization for unstable angina, hospitalization for heart failure, coronary revascularization procedure, peripheral revascularization procedure, cardiogenic shock due to MI, resuscitated sudden death, serious arrhythmia, hospitalization for hypertension, peripheral arterial event. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: up to 84.4 weeks during treatment period
Population: All enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Infection | 127 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | MACE | 4 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | SAE | 30 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Allergy and hypersensitivity | 13 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Injection site reaction | 15 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Depression | 7 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | TEAE | 259 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Suicide/Self-injury | 1 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Malignancy | 0 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Pregnancy | 1 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Pregnancy | 2 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | TEAE | 422 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | SAE | 57 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Infection | 266 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Injection site reaction | 30 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Malignancy | 7 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | MACE | 6 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Allergy and hypersensitivity | 23 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Depression | 10 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)During Treatment Period | Suicide/Self-injury | 0 Participants |
Primary
Percentage of Participants Developing Anti-LY2127399 Antibodies
Participants with treatment-emergent anti-LY2127399 antibodies were participants who had any samples from baseline up to and through Week 72 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants with anti-LY2127399 antibodies=(number of participants with treatment-emergent anti-LY2127399 antibodies / number of participants assessed)\*100.
Time frame: Baseline through Weeks 4, 24, 48 and 72
Population: All participants from Studies BCDO and BCDV with an evaluable baseline anti-LY2127399 antibodies result and a post-baseline anti-LY2127399 antibodies result. Participants missing an evaluable baseline result with a negative post-baseline results were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 120 mg LY2127399 (LY A) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 0.7 percentage of participants |
| 120 mg LY2127399 (LY A) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| 120 mg LY2127399 (LY A) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.0 percentage of participants |
| 120 mg LY2127399 (LY A) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 1.7 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.6 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 0.7 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 0.3 percentage of participants |
| NR LY A to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 3.4 percentage of participants |
| NR LY A to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| NR LY A to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.0 percentage of participants |
| NR LY A to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 1.3 percentage of participants |
| NR LY B to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.0 percentage of participants |
| NR LY B to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| NR LY B to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 1.1 percentage of participants |
| NR LY B to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 1.4 percentage of participants |
| NR Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 1.5 percentage of participants |
| NR Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.0 percentage of participants |
| NR Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| NR Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 0.0 percentage of participants |
| Placebo to LY A | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0 percentage of participants |
| Placebo to LY A | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 2.1 percentage of participants |
| Placebo to LY A | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 1.1 percentage of participants |
| Placebo to LY A | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0 percentage of participants |
| Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 72 | 0.0 percentage of participants |
| Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 24 | 0.0 percentage of participants |
| Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 48 | 0.0 percentage of participants |
| Placebo to LY B | Percentage of Participants Developing Anti-LY2127399 Antibodies | Week 4 | 1.0 percentage of participants |
Secondary
American College of Rheumatology Percent Improvement (ACR-N)
Time frame: Baseline through 240 weeks
Population: Zero participants analyzed. ACR-N data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in CRP
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. CRP data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. DAS28-CRP data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. HAQ-DI data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. SF-36 data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. VAS data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Participants Global Assessment of Disease Activity (VAS)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. Participants Global assessment data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Physicians Global Assessment of Disease Activity (VAS)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. Physicians global assessment data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Swollen Joint Count (66 Joint Count)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. Swollen joint count data was not collected for analysis due to early termination of the study.
Secondary
Change From Baseline in Tender Joint Count (68 Joint Count)
Time frame: Baseline, 240 weeks
Population: Zero participants analyzed. Tender joint count data was not collected for analysis due to early termination of the study.
Secondary
Percentage of Participants With American College of Rheumatology 20% Response (ACR20)
ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants achieving ACR20 response=(number of ACR20 responders / number of participants treated) \* 100. All participants who discontinue study treatment for any reason were defined as NR at that time point and going forward.
Time frame: Baseline through Weeks 12, 24 and 48
Population: All participants from Studies BCDO and BCDV with an evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR20 was missing after carrying forward CRP, last post-baseline ACR20 response was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 120 mg LY2127399 (LY A) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 14.0 percentage of participants |
| 120 mg LY2127399 (LY A) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 37.3 percentage of participants |
| 120 mg LY2127399 (LY A) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 41.9 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 37.0 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 46.1 percentage of participants |
| 90 mg LY2127399 (LY B) | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 15.9 percentage of participants |
| NR LY A to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 18.7 percentage of participants |
| NR LY A to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 30.8 percentage of participants |
| NR LY A to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 29.7 percentage of participants |
| NR LY B to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 16.3 percentage of participants |
| NR LY B to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 21.7 percentage of participants |
| NR LY B to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 7.6 percentage of participants |
| NR Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 27.8 percentage of participants |
| NR Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 25.0 percentage of participants |
| NR Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 16.7 percentage of participants |
| Placebo to LY A | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 8.6 percentage of participants |
| Placebo to LY A | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 6.7 percentage of participants |
| Placebo to LY A | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 6.7 percentage of participants |
| Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 48 | 5.7 percentage of participants |
| Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 24 | 9.4 percentage of participants |
| Placebo to LY B | Percentage of Participants With American College of Rheumatology 20% Response (ACR20) | Week 12 | 4.7 percentage of participants |
Secondary
Percentage of Participants With DAS28-Based European League Against Rheumatism (EULAR-28) Response
Time frame: Baseline through 240 weeks
Population: Zero participants analyzed. EULAR-28 data was not collected for analysis due to early termination of the study.
Other Pre-specified
Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period
Time frame: Up to 84.4 weeks during treatment period and discontinuation from study treatment up to 48 weeks during follow-up period
Population: All enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 120 mg LY2127399 (LY A) | Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period | Treatment Period | 2 Participants |
| 120 mg LY2127399 (LY A) | Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period | Post-Treatment Follow-Up Period | 0 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period | Treatment Period | 4 Participants |
| 90 mg LY2127399 (LY B) | Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period | Post-Treatment Follow-Up Period | 1 Participants |