Arthritis, Rheumatoid
Conditions
Brief summary
The purpose of this study is to examine the safety and efficacy of this antibody in participants with rheumatoid arthritis. Part A of the study is an initial dose escalation phase Part B of the study is a randomized allocation of the entire dosing group to parallel treatment assignments
Interventions
DRUGLY2189102
DRUGplacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of rheumatoid arthritis * regular use of methotrexate * active rheumatoid arthritis
Exclusion criteria
* Juvenile Rheumatoid Arthritis * evidence of tuberculosis * women who are pregnant or become pregnant during study, or are breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline up to Day 98 | Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of s SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | Part A: Day 1 predose and IAI, 2days post infusion, Day 14 and Day 28 predose and IAI, Day 35, 63 (convenient time) | AUC0-168 hr,ss of individual participants was calculated by equation AUC=Dose/Clearance (CL), where the CL was estimated using a population PK model. Time frame for Part B: Day 1 predose, immediately after infusion (IAI), Day 14 and 28: predose and IAI, and Day 63 (Convenient time); |
| Change From Baseline in Simple Disease Activity Index Score (SDAI) | Baseline, Days 7, 21, 35, 63, and 98 | SDAI is calculated as the sum of 5 components: tender joint count (TJC) and swollen joint count (SJC), Patient Global Assessment (PtGA) of disease activity visual analog scale (VAS) and Physician's Global Assessment of Disease Activity (PGA) VAS, and C-reactive protein (CRP). Total Score scale range is 0 (remission) to 86 (high disease activity). A negative change from baseline indicated an improvement. Least Squares (LS) mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time. |
| Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Baseline, Days 7, 21, 35, 63, and 98 | DAS28-4 (crp) is a modification of the original DAS based on TJC and SJC based on 28 joint counts, PGA VAS. DAS28-4 (crp) calculated as: 0.56\*square root (sqrt) (TJC)+0.28\*sqrt(SJC)+0.36\*ln(CRP+1)+0.014\*PGA+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time. |
| Change From Baseline in C-Reactive Protein (CRP) | Baseline, Days 7, 14, 21, 28, 35, 63, and 98 | CRP is a biomarker associated with inflammation and structural damage. A negative change from baseline indicates improvement. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time. |
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Baseline, Days 35, 63, and 98 | HAQ 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 score. If the participant had scores for fewer than 6 categories, the HAQ score was considered missing. The HAQ 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. |
Countries
Poland, United States
Participant flow
Pre-assignment details
Participant Flow reports participants who discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Part B - 0.02 mg/kg/wk LY2189102 Participants were administered a loading dose of 0.04 mg/kg/wk of LY2189102, followed by 0.02 mg/kg/wk for 4 wks, IV. | 20 |
| Part A - 0.1 mg/kg/wk LY2189102 Participants were administered a loading dose of 0.2 mg/kg/wk of LY2189102, followed by 0.1 mg/kg/wk for 4 wks, IV. | 4 |
| Part B - 0.15 mg/kg/wk LY2189102 Participants were administered a loading dose of 0.3 mg/kg/wk of LY2189102, followed by 0.15 mg/kg/wk for 4 wks, IV. | 20 |
| Part A - 0.3 mg/kg/wk LY2189102 Participants were administered a loading dose of 0.6 mg/kg/wk of LY2189102, followed by 0.3 mg/kg/wk for 4 wks, IV. | 4 |
| All Parts - 1.0 mg/kg/wk LY2189102 Participants were administered a loading dose of 2.0 mg/kg/wk of LY2189102, followed by 1.0 mg/kg/wk for 4 wks, IV. | 23 |
| All Parts - 2.5 mg/kg/wk LY2189102 Participants were administered a loading dose of 5.0 mg/kg/wk of LY2189102, followed by 2.5 mg/kg/wk for 4 wks, IV. | 25 |
| All Parts - Placebo Participants were administered matched placebo IV, once weekly for 4 wks. | 25 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A - 0.1 mg/kg/wk LY2189102 | Part B - 0.02 mg/kg/wk LY2189102 | Part B - 0.15 mg/kg/wk LY2189102 | Part A - 0.3 mg/kg/wk LY2189102 | All Parts - 1.0 mg/kg/wk LY2189102 | All Parts - 2.5 mg/kg/wk LY2189102 | All Parts - Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 8 | 53.9 years STANDARD_DEVIATION 10.1 | 50.2 years STANDARD_DEVIATION 14.7 | 51.7 years STANDARD_DEVIATION 14.1 | 52.0 years STANDARD_DEVIATION 12.4 | 54.0 years STANDARD_DEVIATION 13.9 | 55.7 years STANDARD_DEVIATION 10.6 | 53.2 years STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized African | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 3 Participants | 14 Participants | 15 Participants | 4 Participants | 17 Participants | 19 Participants | 19 Participants | 91 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 4 Participants | 5 Participants | 0 Participants | 3 Participants | 5 Participants | 5 Participants | 23 Participants |
| Region of Enrollment Argentina | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 3 Participants | 7 Participants | 6 Participants | 24 Participants |
| Region of Enrollment Hungary | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 15 Participants |
| Region of Enrollment Poland | 0 Participants | 8 Participants | 8 Participants | 0 Participants | 8 Participants | 7 Participants | 7 Participants | 38 Participants |
| Region of Enrollment Spain | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 10 Participants |
| Region of Enrollment United States | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 7 Participants | 4 Participants | 7 Participants | 34 Participants |
| Sex: Female, Male Female | 2 Participants | 17 Participants | 17 Participants | 4 Participants | 16 Participants | 15 Participants | 22 Participants | 93 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 7 Participants | 10 Participants | 3 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 20 | 4 / 4 | 10 / 20 | 4 / 4 | 7 / 23 | 11 / 25 | 14 / 25 |
| serious Total, serious adverse events | 0 / 20 | 0 / 4 | 0 / 20 | 0 / 4 | 0 / 23 | 1 / 25 | 2 / 25 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of s SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline up to Day 98
Population: All data from all randomized participants who received at least 1 dose of study drug according to the assigned treatment.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| 0.02 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 8 Participants |
| 0.1 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| 0.1 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 4 Participants |
| 0.15 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 10 Participants |
| 0.15 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| 0.3 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| 0.3 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 4 Participants |
| 1.0 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 0 Participants |
| 1.0 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 7 Participants |
| 2.5 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | SAEs | 1 Participants |
| 2.5 mg/kg/wk LY2189102 | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 11 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Other Non-Serious AEs | 14 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | SAEs | 2 Participants |
Secondary
Change From Baseline in C-Reactive Protein (CRP)
CRP is a biomarker associated with inflammation and structural damage. A negative change from baseline indicates improvement. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time.
Time frame: Baseline, Days 7, 14, 21, 28, 35, 63, and 98
Population: All data from all randomized participants who received at least 1 dose of study drug according to the assigned treatment.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -12.43 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -8.36 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -9.43 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -7.37 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -11.06 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -11.26 milligrams/deciliter (mg/dL) |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -10.65 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -19.61 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -20.04 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -19.73 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -19.86 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -19.30 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -19.01 milligrams/deciliter (mg/dL) |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -19.18 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -10.18 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -8.33 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -10.85 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -9.63 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -11.51 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -10.23 milligrams/deciliter (mg/dL) |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -12.94 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -19.60 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -21.02 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -20.57 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -19.59 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -20.73 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -20.69 milligrams/deciliter (mg/dL) |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -20.76 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -9.44 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -13.68 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -11.41 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -10.88 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -12.10 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -10.29 milligrams/deciliter (mg/dL) |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -13.53 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -10.27 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -10.14 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -13.35 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -10.42 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -8.29 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -8.66 milligrams/deciliter (mg/dL) |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -13.66 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 21 | -9.69 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 98 | -8.90 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 28 | -12.05 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 7 | -10.64 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 35 | -11.60 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 63 | -9.05 milligrams/deciliter (mg/dL) |
| Placebo | Change From Baseline in C-Reactive Protein (CRP) | Day 14 | -9.04 milligrams/deciliter (mg/dL) |
Secondary
Change From Baseline in Disease Activity Score 28-Joint Count (DAS28)
DAS28-4 (crp) is a modification of the original DAS based on TJC and SJC based on 28 joint counts, PGA VAS. DAS28-4 (crp) calculated as: 0.56\*square root (sqrt) (TJC)+0.28\*sqrt(SJC)+0.36\*ln(CRP+1)+0.014\*PGA+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time.
Time frame: Baseline, Days 7, 21, 35, 63, and 98
Population: All data from all randomized participants who received at least 1 dose of study drug according to the assigned treatment.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.43 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.71 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.06 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -1.22 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -1.49 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.99 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -1.53 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -1.71 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.68 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -2.25 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.08 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -0.88 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.50 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -0.84 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -0.70 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.43 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -1.66 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -2.01 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -2.17 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.84 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.48 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.23 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.06 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -1.02 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -1.13 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.59 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.89 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -1.58 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -1.11 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.56 units on a scale |
| Placebo | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 63 | -0.82 units on a scale |
| Placebo | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 21 | -0.71 units on a scale |
| Placebo | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 35 | -1.04 units on a scale |
| Placebo | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 7 | -0.61 units on a scale |
| Placebo | Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | Day 98 | -1.11 units on a scale |
Secondary
Change From Baseline in Health Assessment Questionnaire (HAQ) Score
HAQ 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 score. If the participant had scores for fewer than 6 categories, the HAQ score was considered missing. The HAQ score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement.
Time frame: Baseline, Days 35, 63, and 98
Population: All data from all randomized participants who received at least 1 dose of study drug according to the assigned treatment.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.25 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.22 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.22 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.15 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.09 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.34 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.11 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.09 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.04 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.04 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.22 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.13 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.19 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.19 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.18 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.71 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.75 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.72 units on a scale |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 98 | -0.31 units on a scale |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 63 | -0.28 units on a scale |
| Placebo | Change From Baseline in Health Assessment Questionnaire (HAQ) Score | Day 35 | -0.29 units on a scale |
Secondary
Change From Baseline in Simple Disease Activity Index Score (SDAI)
SDAI is calculated as the sum of 5 components: tender joint count (TJC) and swollen joint count (SJC), Patient Global Assessment (PtGA) of disease activity visual analog scale (VAS) and Physician's Global Assessment of Disease Activity (PGA) VAS, and C-reactive protein (CRP). Total Score scale range is 0 (remission) to 86 (high disease activity). A negative change from baseline indicated an improvement. Least Squares (LS) mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment \* time.
Time frame: Baseline, Days 7, 21, 35, 63, and 98
Population: All data from all randomized participants who received at least 1 dose of study drug according to the assigned treatment.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -17.45 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -6.81 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -12.43 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -13.96 units on a scale |
| 0.02 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -17.73 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -25.05 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -19.61 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -20.48 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -7.41 units on a scale |
| 0.1 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -24.86 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -13.23 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -10.78 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -5.72 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -10.69 units on a scale |
| 0.15 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -9.27 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -19.66 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -22.59 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -26.16 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -21.72 units on a scale |
| 0.3 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -19.13 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -4.60 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -15.16 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -13.76 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -14.14 units on a scale |
| 1.0 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -14.85 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -7.87 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -22.93 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -19.49 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -13.57 units on a scale |
| 2.5 mg/kg/wk LY2189102 | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -19.12 units on a scale |
| Placebo | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 63 | -13.02 units on a scale |
| Placebo | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 21 | -11.70 units on a scale |
| Placebo | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 35 | -16.63 units on a scale |
| Placebo | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 7 | -8.46 units on a scale |
| Placebo | Change From Baseline in Simple Disease Activity Index Score (SDAI) | Day 98 | -16.70 units on a scale |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102
AUC0-168 hr,ss of individual participants was calculated by equation AUC=Dose/Clearance (CL), where the CL was estimated using a population PK model. Time frame for Part B: Day 1 predose, immediately after infusion (IAI), Day 14 and 28: predose and IAI, and Day 63 (Convenient time);
Time frame: Part A: Day 1 predose and IAI, 2days post infusion, Day 14 and Day 28 predose and IAI, Day 35, 63 (convenient time)
Population: All participants who received at least 1 dose of study drug in part A \& B and had evaluable AUC0-168 hr,ss results.~Per protocol analysis was performed per dose irrespective of study parts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.02 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 196 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 52.5 |
| 0.1 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 902 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 26.8 |
| 0.15 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 1150 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 25.8 |
| 0.3 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 2810 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 29 |
| 1.0 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 6650 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 40.1 |
| 2.5 mg/kg/wk LY2189102 | Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | 18200 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 37.9 |