Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of T-614 versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis
Interventions
DRUGT-614
T-614 is administered twice daily in combination with methotrexate. The daily dose of T-614 is 25 mg for the first 4 weeks and 50 mg for subsequent weeks.
DRUGPlacebo
Placebo is administered twice daily in combination with methotrexate. In placebo group, patients will receive T-614 after completing 28 weeks of treatment.
Sponsors
FUJIFILM Toyama Chemical Co., Ltd.
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have a diagnosis of Rheumatoid Arthritis by the ACR criteria * Age greater or 20 years and less than 70 years old
Exclusion criteria
* Subject who is considered by the investigator, for any reason, to be an unsuitable candidate for the study * Women of childbearing potential who are not practicing a successful method of contraception, or wish to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 24 Last Observation Carried Forward (LOCF) (for T-614 arm and placebo arm) and Week 52 LOCF (for T-614 arm and placebo/T614 arm) | ACR20 response is defined as at least a 20% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PAP, PtGADA and PyGADA | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | Patient's assessment of pain (PAP), patient's global assessment of disease activity (PtGADA) and physician's global assessment of disease activity (PyGADA) each was assessed on a visual analog scale ranging from 0-100 mm, with higher scores indicating severe disease. |
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | HAQ-DI was a participant assessed measure of health assessment, measured on a single scale ranging from 0 (no difficulty) to 3 (unable to do), with higher scores indicating severe disease. |
| Change From Baseline in C-reactive Protein (CRP) | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | Assessment of individual ACR core components i.e. CRP |
| Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | Assessment of individual ACR core components like Tender Joint Counts (TJC) and Swollen Joint Counts (SJC) |
| Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | The DAS28 is a composite score derived from 4 of these measures i.e count of 28 swollen joints, 28 tender joints, measure erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) and to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). DAS28 is assessed as score on scale from 0 to 10 indicating current rheumatoid arthritis (RA) disease activity (0= low disease activity and 10 = high disease activity). |
| Percentage of ACR 50 Criteria Responders | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | ACR50 response is defined as at least a 50% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\]. |
| Percentage of ACR 70 Criteria Responders | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | ACR70 response is defined as at least a 70% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\]. |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | Assessment of individual ACR core components i.e. ESR |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T-614 (Double-blind, 1-28 Weeks) T-614 was administered in combination with methotrexate. Double blind phase-T-614 was orally administered at dosages of 25 mg/day for the first 4 weeks (25 mg once daily) and 50 mg/day (25 mg twice daily) for subsequent 24 weeks. | 164 |
| Placebo (Double-blind, 1-28 Weeks) Placebo was administered in combination with methotrexate. Placebo was administered orally at dosages of a tablet once daily for first 4 weeks and a tablet twice daily for subsequent 24 weeks in double-blind period. | 88 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Phase | Abnormal Laboratory Value | 2 | 0 | 0 | 0 |
| Double-blind Phase | Adverse drug reaction | 2 | 1 | 0 | 0 |
| Double-blind Phase | Drug Refusal Due to Adverse Event | 2 | 0 | 0 | 0 |
| Double-blind Phase | Ineligible after Taking Study Drug | 2 | 3 | 0 | 0 |
| Double-blind Phase | Lack of Efficacy | 7 | 11 | 0 | 0 |
| Double-blind Phase | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Double-blind Phase | Other | 1 | 0 | 0 | 0 |
| Double-blind Phase | Progression of concomitant disease | 1 | 2 | 0 | 0 |
| Extension Phase | Abnormal Laboratory Value | 0 | 0 | 6 | 1 |
| Extension Phase | Adverse drug reaction | 0 | 0 | 6 | 3 |
| Extension Phase | Drug Refusal Due to Adverse Event | 0 | 0 | 4 | 0 |
| Extension Phase | Ineligible after Taking Study Drug | 0 | 0 | 3 | 3 |
| Extension Phase | Lack of Efficacy | 0 | 0 | 8 | 12 |
| Extension Phase | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Extension Phase | Other | 0 | 0 | 2 | 1 |
| Extension Phase | Progression of concomitant disease | 0 | 0 | 4 | 2 |
| Extension Phase | Protocol Violation | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | T-614 (Double-blind, 1-28 Weeks) | Placebo (Double-blind, 1-28 Weeks) | Total |
|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 9.9 | 53.5 Years STANDARD_DEVIATION 10 | 54.3 Years STANDARD_DEVIATION 10 |
| Duration of Rheumatoid Arthritis | 53.8 Months STANDARD_DEVIATION 35 | 50.3 Months STANDARD_DEVIATION 34 | 52.6 Months STANDARD_DEVIATION 34.6 |
| Sex: Female, Male Female | 134 Participants | 70 Participants | 204 Participants |
| Sex: Female, Male Male | 30 Participants | 18 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 135 / 164 | 43 / 88 | 41 / 68 |
| serious Total, serious adverse events | 2 / 164 | 2 / 88 | 0 / 68 |
Outcome results
Primary
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders
ACR20 response is defined as at least a 20% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\].
Time frame: Week 24 Last Observation Carried Forward (LOCF) (for T-614 arm and placebo arm) and Week 52 LOCF (for T-614 arm and placebo/T614 arm)
Population: Full Analysis Set (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 24 LOCF | 69.5 Percentage of Participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 52 LOCF | 71.3 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 24 LOCF | 30.7 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 52 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 24 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | Week 52 LOCF | 72.1 Percentage of Participants |
Secondary
Change From Baseline in C-reactive Protein (CRP)
Assessment of individual ACR core components i.e. CRP
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Baseline | 1.843 mg/dl | Standard Deviation 1.943 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 52 LOCF | -0.609 mg/dl | Standard Deviation 1.841 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 24 LOCF | -0.528 mg/dl | Standard Deviation 2.067 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Baseline | 1.705 mg/dl | Standard Deviation 1.583 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 24 LOCF | 0.47 mg/dl | Standard Deviation 2.028 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 52 LOCF | NA mg/dl | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Baseline | 1.714 mg/dl | Standard Deviation 1.611 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 52 LOCF | -0.581 mg/dl | Standard Deviation 1.866 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in C-reactive Protein (CRP) | Week 24 LOCF | NA mg/dl | — |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
Assessment of individual ACR core components i.e. ESR
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 24 LOCF | -9.3 mm/hr | Standard Deviation 20.8 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 45.6 mm/hr | Standard Deviation 21 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 52 LOCF | -9.4 mm/hr | Standard Deviation 21.3 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 24 LOCF | 2.6 mm/hr | Standard Deviation 19.7 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 41.8 mm/hr | Standard Deviation 22.5 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 52 LOCF | NA mm/hr | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 40.1 mm/hr | Standard Deviation 23.2 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 52 LOCF | -8.8 mm/hr | Standard Deviation 21.5 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Week 24 LOCF | NA mm/hr | — |
Secondary
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
HAQ-DI was a participant assessed measure of health assessment, measured on a single scale ranging from 0 (no difficulty) to 3 (unable to do), with higher scores indicating severe disease.
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 LOCF | -0.3544 score on scale | Standard Deviation 0.4492 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 0.8178 score on scale | Standard Deviation 0.5525 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 52 LOCF | -0.4093 score on scale | Standard Deviation 0.4566 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 LOCF | 0.0256 score on scale | Standard Deviation 0.549 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 0.7344 score on scale | Standard Deviation 0.5117 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 52 LOCF | NA score on scale | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline | 0.7188 score on scale | Standard Deviation 0.5274 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 52 LOCF | -0.2904 score on scale | Standard Deviation 0.4669 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 24 LOCF | NA score on scale | — |
Secondary
Change From Baseline in PAP, PtGADA and PyGADA
Patient's assessment of pain (PAP), patient's global assessment of disease activity (PtGADA) and physician's global assessment of disease activity (PyGADA) each was assessed on a visual analog scale ranging from 0-100 mm, with higher scores indicating severe disease.
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PAP | 47.5 mm | Standard Deviation 22.2 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 24 LOCF | -22 mm | Standard Deviation 23.8 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 52 LOCF | -24 mm | Standard Deviation 24.1 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 24 LOCF | -21.2 mm | Standard Deviation 26.4 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 52 LOCF | -24.3 mm | Standard Deviation 26 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PyGADA | 52.6 mm | Standard Deviation 18.3 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 24 LOCF | -27.1 mm | Standard Deviation 19.3 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 52 LOCF | -29.1 mm | Standard Deviation 22.4 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PtGADA | 47.7 mm | Standard Deviation 24.3 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PtGADA | 50.1 mm | Standard Deviation 23.5 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 24 LOCF | -10.4 mm | Standard Deviation 26.6 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 24 LOCF | -5 mm | Standard Deviation 27.1 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 52 LOCF | NA mm | — |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PyGADA | 53.2 mm | Standard Deviation 19 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PAP | 46.4 mm | Standard Deviation 23.1 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 24 LOCF | -2.5 mm | Standard Deviation 27 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 52 LOCF | NA mm | — |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 52 LOCF | NA mm | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 52 LOCF | -21.4 mm | Standard Deviation 26.6 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PtGADA | 48.4 mm | Standard Deviation 23.6 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PAP: week 24 LOCF | NA mm | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PAP | 44.8 mm | Standard Deviation 22.4 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 24 LOCF | NA mm | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 24 LOCF | NA mm | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Baseline PyGADA | 52.1 mm | Standard Deviation 17.9 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PtGADA: week 52 LOCF | -23.1 mm | Standard Deviation 27.7 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in PAP, PtGADA and PyGADA | Change from baseline in PyGADA: week 52 LOCF | -29.9 mm | Standard Deviation 24.4 |
Secondary
Change From Baseline in Tender Joint Counts and Swollen Joint Counts
Assessment of individual ACR core components like Tender Joint Counts (TJC) and Swollen Joint Counts (SJC)
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: TJC | 12.5 joint counts | Standard Deviation 6.5 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: TJC | -7.4 joint counts | Standard Deviation 6 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: TJC | -8.4 joint counts | Standard Deviation 6.1 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: SJC | 11.5 joint counts | Standard Deviation 6.3 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: SJC | -6.5 joint counts | Standard Deviation 5.9 |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: SJC | -7.1 joint counts | Standard Deviation 6.8 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: SJC | NA joint counts | — |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: TJC | 13.3 joint counts | Standard Deviation 8.1 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: SJC | 11.1 joint counts | Standard Deviation 5.7 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: SJC | -2.9 joint counts | Standard Deviation 6.7 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: TJC | -4.6 joint counts | Standard Deviation 7.8 |
| Placebo (Double-blind, 1-28 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: TJC | NA joint counts | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: TJC | NA joint counts | — |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: TJC | -9.9 joint counts | Standard Deviation 7.6 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 52 LOCF: SJC | -6.3 joint counts | Standard Deviation 6.5 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: SJC | 10.9 joint counts | Standard Deviation 5.8 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Baseline: TJC | 13.8 joint counts | Standard Deviation 8.5 |
| Placebo/T-614 (Extension, 29-52 Weeks) | Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Change from baseline at week 24 LOCF: SJC | NA joint counts | — |
Secondary
Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2)
The DAS28 is a composite score derived from 4 of these measures i.e count of 28 swollen joints, 28 tender joints, measure erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) and to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). DAS28 is assessed as score on scale from 0 to 10 indicating current rheumatoid arthritis (RA) disease activity (0= low disease activity and 10 = high disease activity).
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 24 LOCF | 45 participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 52 LOCF | 56 participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 24 LOCF | 78 participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 52 LOCF | 88 participants |
| Placebo (Double-blind, 1-28 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 52 LOCF | NA participants |
| Placebo (Double-blind, 1-28 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 24 LOCF | 8 participants |
| Placebo (Double-blind, 1-28 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 24 LOCF | 18 participants |
| Placebo (Double-blind, 1-28 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 52 LOCF | NA participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 52 LOCF | 38 participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 52 LOCF | 23 participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Low Disease Activity: week 24 LOCF | NA participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | Remission: week 24 LOCF | NA participants |
Secondary
Percentage of ACR 50 Criteria Responders
ACR50 response is defined as at least a 50% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\].
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: Full Analysis Set (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of ACR 50 Criteria Responders | Week 24 LOCF | 38.4 Percentage of Participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of ACR 50 Criteria Responders | Week 52 LOCF | 49.4 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of ACR 50 Criteria Responders | Week 24 LOCF | 15.9 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of ACR 50 Criteria Responders | Week 52 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of ACR 50 Criteria Responders | Week 24 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of ACR 50 Criteria Responders | Week 52 LOCF | 45.6 Percentage of Participants |
Secondary
Percentage of ACR 70 Criteria Responders
ACR70 response is defined as at least a 70% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant \[erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\].
Time frame: Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm)
Population: FAS (Double-blind), Efficacy Analysis Set (Extension)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of ACR 70 Criteria Responders | Week 24 LOCF | 17.1 Percentage of Participants |
| T-614 (Double-blind, 1-28 Weeks) and (Extension, 29-52 Weeks) | Percentage of ACR 70 Criteria Responders | Week 52 LOCF | 23.8 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of ACR 70 Criteria Responders | Week 24 LOCF | 5.7 Percentage of Participants |
| Placebo (Double-blind, 1-28 Weeks) | Percentage of ACR 70 Criteria Responders | Week 52 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of ACR 70 Criteria Responders | Week 24 LOCF | NA Percentage of Participants |
| Placebo/T-614 (Extension, 29-52 Weeks) | Percentage of ACR 70 Criteria Responders | Week 52 LOCF | 22.1 Percentage of Participants |