Arthritis, Rheumatoid
Conditions
Keywords
active, rheumatoid, arthritis, anti CD20
Brief summary
This study will evaluate the efficacy and safety of two dosing regimens of a compound known as TRU-015 in combination with methotrexate (MTX) in patients with active rheumatoid arthritis.
Interventions
DRUGTRU-015
IV 800 mg TRU-015 at Baseline (both arms) and Week 24 (both arms); corresponding IV Placebo at Week 12 and Week 36 (both arms).
DRUGMethylprednisolone
IV 100 mg Methylprednisolone at Baseline (both arms), Week 12 (arm 1a) and Week 24 (both arms); corresponding IV Placebo at Week 12 (Arm 1b) and Week 36 (both arms).
DRUGPrednisone
Oral 20 mg tablets Prednisone at Baseline (both arms), Week 12 (arm 1a), and Week 24 (both arms); corresponding Oral Placebo at Week 12 (Arm 1b) and Week 36 (both arms)
Sponsors
Trubion Pharmaceuticals/Emergent BioSolutions Inc.
Pfizer
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of active seropositive rheumatoid arthritis on a stable dose of methotrexate (7.5-25 mg weekly) for at least 12 weeks with or without a history of anti-TNF use.
Exclusion criteria
* Any prior use of rituximab or other B cell depleting agents. * Any significant health problem other than rheumatoid arthritis * Clinically significant laboratory abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24 | Week 24 | ACR50 response: greater than or equal to (\>=) 50 percent (%) improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and C-Reactive Protein (CRP). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| General Health Visual Analog Scale (VAS) | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 100 mm line (VAS) marked by participant. Participants were asked, How do you feel concerning your arthritis? Total possible score range, 0 mm = very well to 100 mm = extremely bad. |
| Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The overall disability index computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Disease Activity Score Based on 28-joints Count (DAS28) | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's general health visual analog scale (scores ranging 0 \[very well\] to 100 mm \[extremely bad\]). DAS28 less than or equal to (=\<) 3.2 = low disease activity, DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity. |
| 36-Item Short-Form Health Survey (SF-36) | Baseline, Week 12, 24, 36, 52 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). |
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | Baseline, Week 12, 24, 36, 52 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates a better health state. |
| Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) | Baseline, Week 12, 24, 36, 52 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. |
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score | Baseline, Week 12, 24, 36, 52 | FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). |
| Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI-RA) Score | Baseline, Week 12, 24, 36, 52 | WPAI-RA consisted of 6 items, a binary question on current employment, 3 questions on hours of work and work-loss, and 2 questions based on 0-10 point scale to judge how RA affects productivity at work and outside of work (0 = no effect on work and 10 = completely prevented from working). Four scores are derived: percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health and percent activity impairment due to health. Total possible score range: 0 to 100, where 0 = no impairment and 100 = completely impaired. |
| Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. |
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | ACR20 response: \>= 20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP. |
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2, 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52 | ACR50 response: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP. |
| Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | ACR70 response: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP. |
| Number of Tender Joints | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | The number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. |
| Number of Swollen Joints | Baseline. Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | The number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. |
| Duration of Morning Stiffness | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if morning stiffness was continuing, average of duration of stiffness over the past 3 days was reported; if stiffness persisted the entire day, 1440 minutes \[24 hours\*60 minutes\] was recorded). |
| Visual Analogue Scale for Pain (VAS-pain) | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 = no pain to 100 = worst possible pain. |
| Patient Global Assessment (PtGA) of Disease Activity | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Measured using a 0-10 point scale, where 0 = no disease activity and 10 = extreme disease activity. |
| Physician Global Assessment (PGA) of Disease Activity | Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Physician Global Assessment of Disease Activity was measured on a 0 to 10 point scale, where 0 = no disease activity and 10 = extreme disease activity. |
Countries
Belgium, Canada, France, Germany, Hungary, Mexico, Netherlands, Romania, Serbia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo infusion, matched to TRU-015 (800 mg), IV along with methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at baseline. Placebo infusion, matched to TRU-015 (800 mg), IV along with methylprednisolone 100 mg or matching placebo IV 1 hr prior to infusion and prednisone 20 mg capsule or matching placebo orally each day for 2 days prior to and on the morning of the infusion at Week 12. TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at Week 24. TRU-015 (800 mg) infusion or matching placebo IV, methylprednisolone 100 mg or matching placebo IV 1 hr prior to infusion and prednisone 20 mg capsule or matching placebo orally each day for 2 days prior to and on the morning of infusion at Week 36. | 74 |
| TRU-015 Single Dose TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at baseline. Placebo infusion, matched to TRU-015 (800 mg), IV, methylprednisolone 100 mg or matching placebo IV 1 hr prior to infusion and prednisone 20 mg capsule or matching placebo orally each day for 2 days prior to and on the morning of infusion at Week 12. TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at Week 24. Placebo infusion, matched to TRU-015 (800 mg) IV along with placebo matched to methylprednisolone 100 mg IV 1 hr prior to infusion and placebo matched to prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at Week 36. | 75 |
| TRU-015 Induction Dose TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at baseline. TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule or matching placebo orally each day for 2 days prior to and on the morning of infusion at Week 12. Placebo infusion, matched to TRU-015 (800 mg), IV, placebo matched to methylprednisolone 100 mg IV 1 hr prior to infusion and placebo capsule matched to prednisone 20 mg orally each day for 2 days prior to and on the morning of infusion at Week 24. TRU-015 (800 mg) infusion IV, methylprednisolone 100 mg IV 1 hr prior to infusion and prednisone 20 mg capsule orally each day for 2 days prior to and on the morning of infusion at Week 36. | 73 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Between Part A and Part B | Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Part A: Baseline to Week 24 | Adverse Event | 4 | 4 | 8 | 0 | 0 |
| Part A: Baseline to Week 24 | Death | 1 | 0 | 0 | 0 | 0 |
| Part A: Baseline to Week 24 | Failed to Return | 1 | 0 | 0 | 0 | 0 |
| Part A: Baseline to Week 24 | Investigator Request | 1 | 1 | 1 | 0 | 0 |
| Part A: Baseline to Week 24 | Lack of Efficacy | 3 | 1 | 0 | 0 | 0 |
| Part A: Baseline to Week 24 | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 |
| Part A: Baseline to Week 24 | Other | 1 | 8 | 5 | 0 | 0 |
| Part A: Baseline to Week 24 | Withdrawal by Subject | 0 | 3 | 3 | 0 | 0 |
| Part B: Week 24 to Week 52 | Adverse Event | 0 | 1 | 1 | 1 | 0 |
| Part B: Week 24 to Week 52 | Discontinuation of Study by Sponsor | 0 | 11 | 14 | 3 | 7 |
| Part B: Week 24 to Week 52 | Lack of Efficacy | 0 | 1 | 1 | 0 | 0 |
| Part B: Week 24 to Week 52 | Other | 0 | 0 | 5 | 0 | 1 |
| Part B: Week 24 to Week 52 | Physician Decision | 0 | 1 | 1 | 0 | 0 |
| Part B: Week 24 to Week 52 | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Part B: Week 24 to Week 52 | Withdrawal by Subject | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | TRU-015 Single Dose | TRU-015 Induction Dose | Total |
|---|---|---|---|---|
| Age Continuous | 50.62 years STANDARD_DEVIATION 11.07 | 52.99 years STANDARD_DEVIATION 11.33 | 52.55 years STANDARD_DEVIATION 13 | 52.05 years STANDARD_DEVIATION 11.81 |
| Sex: Female, Male Female | 64 Participants | 62 Participants | 59 Participants | 185 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 14 Participants | 37 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 | 25 / 74 | 27 / 75 | 25 / 73 | 22 / 56 | 12 / 55 | 18 / 31 | 14 / 32 |
| serious Total, serious adverse events | 7 / 74 | 4 / 75 | 7 / 73 | 2 / 56 | 2 / 55 | 0 / 31 | 0 / 32 |
Outcome results
Primary
Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24
ACR50 response: greater than or equal to (\>=) 50 percent (%) improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and C-Reactive Protein (CRP).
Time frame: Week 24
Population: Modified intent-to-treat (mITT) population included all randomized participants who received any portion of test article. Last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24 | 16.2 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24 | 29.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24 | 27.4 percentage of participants |
Comparison: A 2-sided Cochran-Mantel-Haenszel test (CMH), stratified by prior anti-tumor necrosis factor (anti-TNF) use and geographic region, was used.p-value: 0.061Cochran-Mantel-Haenszel
Comparison: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.12Cochran-Mantel-Haenszel
Secondary
36-Item Short-Form Health Survey (SF-36)
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time frame: Baseline, Week 12, 24, 36, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
Disease Activity Score Based on 28-joints Count (DAS28)
DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's general health visual analog scale (scores ranging 0 \[very well\] to 100 mm \[extremely bad\]). DAS28 less than or equal to (=\<) 3.2 = low disease activity, DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Baseline | 6.1 units on a scale | Standard Deviation 0.7 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 2 | 5.4 units on a scale | Standard Deviation 1 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 4 | 5.2 units on a scale | Standard Deviation 1.1 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 8 | 5.1 units on a scale | Standard Deviation 1.3 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 12 | 5.0 units on a scale | Standard Deviation 1.3 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 16 | 4.7 units on a scale | Standard Deviation 1.5 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 20 | 4.7 units on a scale | Standard Deviation 1.4 |
| Placebo | Disease Activity Score Based on 28-joints Count (DAS28) | Week 24 | 4.7 units on a scale | Standard Deviation 1.4 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 4 | 4.9 units on a scale | Standard Deviation 1.4 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 20 | 4.0 units on a scale | Standard Deviation 1.3 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 8 | 4.6 units on a scale | Standard Deviation 1.3 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 12 | 4.3 units on a scale | Standard Deviation 1.3 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 16 | 3.9 units on a scale | Standard Deviation 1.4 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Baseline | 5.8 units on a scale | Standard Deviation 0.9 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 2 | 5.1 units on a scale | Standard Deviation 1.3 |
| TRU-015 Single Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 24 | 4.1 units on a scale | Standard Deviation 1.3 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 4 | 5.0 units on a scale | Standard Deviation 1.4 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 2 | 5.3 units on a scale | Standard Deviation 1.3 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Baseline | 6.1 units on a scale | Standard Deviation 1 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 8 | 4.7 units on a scale | Standard Deviation 1.3 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 20 | 4.1 units on a scale | Standard Deviation 1.4 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 16 | 4.3 units on a scale | Standard Deviation 1.4 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 12 | 4.6 units on a scale | Standard Deviation 1.4 |
| TRU-015 Induction Dose | Disease Activity Score Based on 28-joints Count (DAS28) | Week 24 | 4.0 units on a scale | Standard Deviation 1.5 |
Secondary
Duration of Morning Stiffness
Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if morning stiffness was continuing, average of duration of stiffness over the past 3 days was reported; if stiffness persisted the entire day, 1440 minutes \[24 hours\*60 minutes\] was recorded).
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates a better health state.
Time frame: Baseline, Week 12, 24, 36, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.
Time frame: Baseline, Week 12, 24, 36, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
Time frame: Baseline, Week 12, 24, 36, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
General Health Visual Analog Scale (VAS)
100 mm line (VAS) marked by participant. Participants were asked, How do you feel concerning your arthritis? Total possible score range, 0 mm = very well to 100 mm = extremely bad.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.
Secondary
Health Assessment Questionnaire Disability Index (HAQ-DI)
HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The overall disability index computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 1.8 units on a scale | Standard Deviation 0.6 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 1.5 units on a scale | Standard Deviation 0.6 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 1.4 units on a scale | Standard Deviation 0.7 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 1.5 units on a scale | Standard Deviation 0.7 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 1.5 units on a scale | Standard Deviation 0.7 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 16 | 1.4 units on a scale | Standard Deviation 0.7 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 20 | 1.4 units on a scale | Standard Deviation 0.7 |
| Placebo | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 | 1.4 units on a scale | Standard Deviation 0.6 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 1.4 units on a scale | Standard Deviation 0.7 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 20 | 1.2 units on a scale | Standard Deviation 0.7 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 1.3 units on a scale | Standard Deviation 0.6 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 1.3 units on a scale | Standard Deviation 0.6 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 16 | 1.2 units on a scale | Standard Deviation 0.6 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 1.7 units on a scale | Standard Deviation 0.6 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 1.4 units on a scale | Standard Deviation 0.7 |
| TRU-015 Single Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 | 1.2 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 1.3 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 1.3 units on a scale | Standard Deviation 0.6 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 1.6 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 1.2 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 20 | 1.0 units on a scale | Standard Deviation 0.8 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 16 | 1.1 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 1.1 units on a scale | Standard Deviation 0.7 |
| TRU-015 Induction Dose | Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 | 1.0 units on a scale | Standard Deviation 0.8 |
Secondary
Number of Swollen Joints
The number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.
Time frame: Baseline. Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Number of Swollen Joints | Baseline | 12.2 swollen joints | Standard Deviation 4.4 |
| Placebo | Number of Swollen Joints | Week 2 | 9.5 swollen joints | Standard Deviation 5.7 |
| Placebo | Number of Swollen Joints | Week 4 | 7.8 swollen joints | Standard Deviation 5.3 |
| Placebo | Number of Swollen Joints | Week 8 | 7.0 swollen joints | Standard Deviation 5.7 |
| Placebo | Number of Swollen Joints | Week 12 | 7.6 swollen joints | Standard Deviation 5.8 |
| Placebo | Number of Swollen Joints | Week 16 | 6.1 swollen joints | Standard Deviation 5.4 |
| Placebo | Number of Swollen Joints | Week 20 | 6.0 swollen joints | Standard Deviation 5.4 |
| Placebo | Number of Swollen Joints | Week 24 | 6.2 swollen joints | Standard Deviation 5.5 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 4 | 8.5 swollen joints | Standard Deviation 6.4 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 20 | 4.8 swollen joints | Standard Deviation 4.6 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 8 | 6.9 swollen joints | Standard Deviation 5.2 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 12 | 6.0 swollen joints | Standard Deviation 4.9 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 16 | 5.1 swollen joints | Standard Deviation 5.2 |
| TRU-015 Single Dose | Number of Swollen Joints | Baseline | 12.3 swollen joints | Standard Deviation 6 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 2 | 9.0 swollen joints | Standard Deviation 6.5 |
| TRU-015 Single Dose | Number of Swollen Joints | Week 24 | 4.7 swollen joints | Standard Deviation 4.6 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 4 | 9.0 swollen joints | Standard Deviation 6.2 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 2 | 10.2 swollen joints | Standard Deviation 6.2 |
| TRU-015 Induction Dose | Number of Swollen Joints | Baseline | 13.9 swollen joints | Standard Deviation 5.7 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 8 | 7.7 swollen joints | Standard Deviation 5.6 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 20 | 5.1 swollen joints | Standard Deviation 4.9 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 16 | 5.9 swollen joints | Standard Deviation 4.7 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 12 | 7.1 swollen joints | Standard Deviation 5.5 |
| TRU-015 Induction Dose | Number of Swollen Joints | Week 24 | 5.0 swollen joints | Standard Deviation 5 |
Secondary
Number of Tender Joints
The number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Number of Tender Joints | Baseline | 17.0 tender joints | Standard Deviation 6.1 |
| Placebo | Number of Tender Joints | Week 2 | 13.6 tender joints | Standard Deviation 7 |
| Placebo | Number of Tender Joints | Week 4 | 11.9 tender joints | Standard Deviation 7 |
| Placebo | Number of Tender Joints | Week 8 | 11.7 tender joints | Standard Deviation 8.4 |
| Placebo | Number of Tender Joints | Week 12 | 11.0 tender joints | Standard Deviation 7.9 |
| Placebo | Number of Tender Joints | Week 16 | 9.4 tender joints | Standard Deviation 7.9 |
| Placebo | Number of Tender Joints | Week 20 | 9.0 tender joints | Standard Deviation 7.2 |
| Placebo | Number of Tender Joints | Week 24 | 9.4 tender joints | Standard Deviation 7.5 |
| TRU-015 Single Dose | Number of Tender Joints | Week 4 | 10.7 tender joints | Standard Deviation 7.7 |
| TRU-015 Single Dose | Number of Tender Joints | Week 20 | 7.6 tender joints | Standard Deviation 7.3 |
| TRU-015 Single Dose | Number of Tender Joints | Week 8 | 9.8 tender joints | Standard Deviation 6.7 |
| TRU-015 Single Dose | Number of Tender Joints | Week 12 | 8.8 tender joints | Standard Deviation 6.9 |
| TRU-015 Single Dose | Number of Tender Joints | Week 16 | 7.3 tender joints | Standard Deviation 7 |
| TRU-015 Single Dose | Number of Tender Joints | Baseline | 16.8 tender joints | Standard Deviation 7 |
| TRU-015 Single Dose | Number of Tender Joints | Week 2 | 11.9 tender joints | Standard Deviation 7.4 |
| TRU-015 Single Dose | Number of Tender Joints | Week 24 | 8.1 tender joints | Standard Deviation 7.6 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 4 | 11.6 tender joints | Standard Deviation 7.7 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 2 | 13.0 tender joints | Standard Deviation 7.7 |
| TRU-015 Induction Dose | Number of Tender Joints | Baseline | 17.7 tender joints | Standard Deviation 6.2 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 8 | 10.1 tender joints | Standard Deviation 7.4 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 20 | 7.6 tender joints | Standard Deviation 7.1 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 16 | 8.4 tender joints | Standard Deviation 7.2 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 12 | 9.6 tender joints | Standard Deviation 7.7 |
| TRU-015 Induction Dose | Number of Tender Joints | Week 24 | 7.6 tender joints | Standard Deviation 7.4 |
Secondary
Patient Global Assessment (PtGA) of Disease Activity
Measured using a 0-10 point scale, where 0 = no disease activity and 10 = extreme disease activity.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 24 | 5.3 units on a scale | Standard Deviation 2 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 2 | 6.2 units on a scale | Standard Deviation 2.1 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 4 | 6.0 units on a scale | Standard Deviation 1.8 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 8 | 6.2 units on a scale | Standard Deviation 2.1 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 12 | 5.9 units on a scale | Standard Deviation 2.1 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 16 | 6.6 units on a scale | Standard Deviation 9.2 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Week 20 | 5.5 units on a scale | Standard Deviation 2.1 |
| Placebo | Patient Global Assessment (PtGA) of Disease Activity | Baseline | 7.3 units on a scale | Standard Deviation 1.6 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 4 | 5.4 units on a scale | Standard Deviation 2.4 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 20 | 4.5 units on a scale | Standard Deviation 2.3 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 8 | 5.2 units on a scale | Standard Deviation 2.4 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 12 | 4.8 units on a scale | Standard Deviation 2.3 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 24 | 4.6 units on a scale | Standard Deviation 2.3 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 16 | 4.4 units on a scale | Standard Deviation 2.3 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Baseline | 6.9 units on a scale | Standard Deviation 1.9 |
| TRU-015 Single Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 2 | 5.6 units on a scale | Standard Deviation 2.4 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 2 | 5.6 units on a scale | Standard Deviation 2.3 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 24 | 4.7 units on a scale | Standard Deviation 2.7 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Baseline | 7.0 units on a scale | Standard Deviation 2.3 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 8 | 5.3 units on a scale | Standard Deviation 2.3 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 20 | 4.5 units on a scale | Standard Deviation 2.4 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 16 | 4.6 units on a scale | Standard Deviation 2.5 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 12 | 5.2 units on a scale | Standard Deviation 2.4 |
| TRU-015 Induction Dose | Patient Global Assessment (PtGA) of Disease Activity | Week 4 | 5.6 units on a scale | Standard Deviation 2.4 |
Secondary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
ACR20 response: \>= 20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.
Time frame: Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 31.1 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 16 | 41.9 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 31.1 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 17.6 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 24 | 43.2 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 20 | 47.3 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 31.1 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 52.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 21.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 34.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 44.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 16 | 64.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 20 | 62.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 24 | 61.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 16 | 61.6 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 34.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 24 | 67.1 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 20 | 64.4 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 49.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 42.5 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 26.0 percentage of participants |
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.57Cochran-Mantel-Haenszel
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.2Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.616Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.671Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.108Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.174Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.01Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.029Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.006Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.021Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.062Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.049Cochran-Mantel-Haenszel
Comparison: Week 24: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.03Cochran-Mantel-Haenszel
Comparison: Week 24: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.005Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response
ACR50 response: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.
Time frame: Week 2, 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 20 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 0.0 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 6.8 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 12.2 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 14.9 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 16 | 16.2 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 20 | 16.2 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 20 | 28.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 8.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 16.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 16 | 30.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 8.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 10.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 6.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 8.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 20 | 28.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 13.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 6.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 16 | 31.5 percentage of participants |
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.014Cochran-Mantel-Haenszel
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.025Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.794Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.966Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.77Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.456Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.88Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.814Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.042Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.035Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.086Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.082Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response
ACR70 response: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.
Time frame: Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 1.4 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 16 | 6.8 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 1.4 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 0.0 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 24 | 2.7 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 20 | 2.7 percentage of participants |
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 1.4 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 2.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 1.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 1.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 2.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 16 | 8.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 20 | 6.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 24 | 9.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 16 | 6.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 0.0 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 24 | 9.6 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 20 | 6.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 2.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 1.4 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 1.4 percentage of participants |
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.325Cochran-Mantel-Haenszel
Comparison: Week 2: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.338Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.983Cochran-Mantel-Haenszel
Comparison: Week 4: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.296Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.575Cochran-Mantel-Haenszel
Comparison: Week 8: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 1Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.573Cochran-Mantel-Haenszel
Comparison: Week 12: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.563Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.768Cochran-Mantel-Haenszel
Comparison: Week 16: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.977Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.249Cochran-Mantel-Haenszel
Comparison: Week 20: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.268Cochran-Mantel-Haenszel
Comparison: Week 24: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.089Cochran-Mantel-Haenszel
Comparison: Week 24: A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.079Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1.
Time frame: Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: moderate response | 44.6 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: moderate response | 44.6 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: no response | 40.5 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: no response | 47.3 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: good response | 5.4 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: moderate response | 40.5 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: good response | 9.5 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: good response | 1.4 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: good response | 18.9 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: moderate response | 39.2 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: good response | 14.9 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: no response | 51.4 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: moderate response | 39.2 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: no response | 40.5 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: no response | 44.6 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: no response | 55.4 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: no response | 64.9 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: moderate response | 37.8 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: good response | 8.1 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: moderate response | 33.8 percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: good response | 17.6 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: no response | 26.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: good response | 6.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: moderate response | 38.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: no response | 54.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: good response | 14.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: moderate response | 41.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: no response | 44.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: good response | 14.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: moderate response | 44.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: no response | 41.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: good response | 21.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: moderate response | 53.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: no response | 25.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: good response | 34.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: moderate response | 41.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: no response | 24.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: good response | 29.3 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: moderate response | 52.0 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: no response | 18.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: good response | 26.7 percentage of participants |
| TRU-015 Single Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: moderate response | 46.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: moderate response | 53.4 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: no response | 57.5 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: no response | 23.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: good response | 12.3 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: good response | 2.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: good response | 26.0 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: no response | 46.6 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: moderate response | 50.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: moderate response | 54.8 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: moderate response | 45.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 2: moderate response | 39.7 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20: no response | 19.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: moderate response | 52.1 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4: good response | 8.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: no response | 31.5 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12: good response | 16.4 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: no response | 19.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: good response | 20.5 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8: no response | 34.2 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24: good response | 30.1 percentage of participants |
| TRU-015 Induction Dose | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16: moderate response | 56.2 percentage of participants |
Comparison: Week 2: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.106Cochran-Mantel-Haenszel
Comparison: Week 2: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.322Cochran-Mantel-Haenszel
Comparison: Week 4 Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.059Cochran-Mantel-Haenszel
Comparison: Week 4: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.25Cochran-Mantel-Haenszel
Comparison: Week 8: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.255Cochran-Mantel-Haenszel
Comparison: Week 8: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.105Cochran-Mantel-Haenszel
Comparison: Week 12: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.001Cochran-Mantel-Haenszel
Comparison: Week 12: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.019Cochran-Mantel-Haenszel
Comparison: Week 16: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.011Cochran-Mantel-Haenszel
Comparison: Week 16: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.113Cochran-Mantel-Haenszel
Comparison: Week 20: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.002Cochran-Mantel-Haenszel
Comparison: Week 20: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.006Cochran-Mantel-Haenszel
Comparison: Week 24: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.034Cochran-Mantel-Haenszel
Comparison: Week 24: Good response- A 2-sided CMH test, stratified by prior anti-TNF use and geographic region, was used.p-value: 0.003Cochran-Mantel-Haenszel
Secondary
Physician Global Assessment (PGA) of Disease Activity
Physician Global Assessment of Disease Activity was measured on a 0 to 10 point scale, where 0 = no disease activity and 10 = extreme disease activity.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Baseline | 6.8 units on a scale | Standard Deviation 1.3 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 2 | 5.5 units on a scale | Standard Deviation 1.5 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 4 | 5.0 units on a scale | Standard Deviation 1.9 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 8 | 5.0 units on a scale | Standard Deviation 2.2 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 12 | 4.8 units on a scale | Standard Deviation 2.1 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 16 | 4.6 units on a scale | Standard Deviation 2.4 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 20 | 4.4 units on a scale | Standard Deviation 2.1 |
| Placebo | Physician Global Assessment (PGA) of Disease Activity | Week 24 | 4.3 units on a scale | Standard Deviation 2.2 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 4 | 5.0 units on a scale | Standard Deviation 2.3 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 20 | 3.8 units on a scale | Standard Deviation 1.8 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 8 | 4.1 units on a scale | Standard Deviation 2.1 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 12 | 4.1 units on a scale | Standard Deviation 2.1 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 16 | 3.7 units on a scale | Standard Deviation 2.1 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Baseline | 6.4 units on a scale | Standard Deviation 1.6 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 2 | 5.1 units on a scale | Standard Deviation 2.2 |
| TRU-015 Single Dose | Physician Global Assessment (PGA) of Disease Activity | Week 24 | 3.7 units on a scale | Standard Deviation 2.1 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 4 | 4.9 units on a scale | Standard Deviation 2.1 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 2 | 5.2 units on a scale | Standard Deviation 1.9 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Baseline | 6.6 units on a scale | Standard Deviation 1.7 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 8 | 4.4 units on a scale | Standard Deviation 2.1 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 20 | 3.6 units on a scale | Standard Deviation 2.2 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 16 | 3.6 units on a scale | Standard Deviation 2.1 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 12 | 4.3 units on a scale | Standard Deviation 2.3 |
| TRU-015 Induction Dose | Physician Global Assessment (PGA) of Disease Activity | Week 24 | 3.6 units on a scale | Standard Deviation 2.4 |
Secondary
Visual Analogue Scale for Pain (VAS-pain)
100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 = no pain to 100 = worst possible pain.
Time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: mITT population included all randomized participants who received any portion of test article. LOCF method was used to impute missing values. Data for time points after Week 24 were not analyzed because of early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Baseline | 65.4 mm | Standard Deviation 17.9 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 2 | 53.0 mm | Standard Deviation 21.2 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 4 | 53.6 mm | Standard Deviation 20.3 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 8 | 56.4 mm | Standard Deviation 23 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 12 | 54.3 mm | Standard Deviation 21.6 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 16 | 51.1 mm | Standard Deviation 24.2 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 20 | 51.1 mm | Standard Deviation 21.6 |
| Placebo | Visual Analogue Scale for Pain (VAS-pain) | Week 24 | 49.2 mm | Standard Deviation 22.2 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 4 | 48.9 mm | Standard Deviation 25.9 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 20 | 39.5 mm | Standard Deviation 24.2 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 8 | 45.8 mm | Standard Deviation 24 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 12 | 42.3 mm | Standard Deviation 24.1 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 16 | 39.3 mm | Standard Deviation 24.4 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Baseline | 62.5 mm | Standard Deviation 20.7 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 2 | 47.7 mm | Standard Deviation 25.2 |
| TRU-015 Single Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 24 | 39.2 mm | Standard Deviation 25 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 4 | 49.0 mm | Standard Deviation 24.2 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 2 | 49.6 mm | Standard Deviation 24.6 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Baseline | 61.6 mm | Standard Deviation 23 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 8 | 47.0 mm | Standard Deviation 24.5 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 20 | 39.1 mm | Standard Deviation 25.7 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 16 | 40.8 mm | Standard Deviation 25.2 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 12 | 44.8 mm | Standard Deviation 25.4 |
| TRU-015 Induction Dose | Visual Analogue Scale for Pain (VAS-pain) | Week 24 | 43.9 mm | Standard Deviation 28.3 |
Secondary
Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI-RA) Score
WPAI-RA consisted of 6 items, a binary question on current employment, 3 questions on hours of work and work-loss, and 2 questions based on 0-10 point scale to judge how RA affects productivity at work and outside of work (0 = no effect on work and 10 = completely prevented from working). Four scores are derived: percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health and percent activity impairment due to health. Total possible score range: 0 to 100, where 0 = no impairment and 100 = completely impaired.
Time frame: Baseline, Week 12, 24, 36, 52
Population: Data was not analyzed because development of TRU-015 was discontinued as results of primary analysis did not meet the predefined efficacy criteria.