Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT02831855
- Lead Sponsor
- Pfizer
- Brief Summary
This study is designed to evaluate the efficacy and safety of tofacitinib modified release formulation (11mg QD) versus tofacitinib modified release formulation plus continued methotrexate treatment in subjects with moderate to severe rheumatoid arthritis who are insufficiently responding to their stable dose of methotrexate treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 694
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CP-690,550 and methotrexate CP-690,550 Open-label tofacitinib tablet and blinded methotrexate capsule CP-690,550 and placebo Placebo open-label tofacitinib tablet and blinded matching placebo for methotrexate capsule CP-690,550 and methotrexate Methotrexate Open-label tofacitinib tablet and blinded methotrexate capsule
- Primary Outcome Measures
Name Time Method Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and participant global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
- Secondary Outcome Measures
Name Time Method Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive Protein [CRP]) at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter \[mg/L\]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<= 3.2 implied low disease activity and \> 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \< 2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.
Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 millimeter (mm) VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) less than (\<) 2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and physician global assessment of arthritis (PhyGA). PtGA and PhyGA both were assessed on 0-10 centimeter (cm) VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicates low disease activity and a score of \<=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Double Blind Phase: Percentage of Participants With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48 Weeks 36 and 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicated worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm; ln = natural logarithm, sqrt = square root of.
Double Blind Phase: Percentage of Participants With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48 Weeks 36 and 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root of.
Double Blind Phase: Percentage of Participants With LDA Assessed by CDAI <=10 at Weeks 36 and 48 Weeks 36 and 48 CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. Percentage of participants with CDAI \<=10 were reported. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Double Blind Phase: Percentage of Participants With LDA Assessed by SDAI <=11 at Weeks 36 and 48 Weeks 36 and 48 SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicated low disease activity and a score of \<=3.3 indicated remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Double Blind Phase: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48 Weeks 36 and 48 ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), CRP (in mg/dL), and PtGA (VAS: 0 cm \[very well\] to 10 cm \[worst\], higher scores indicated worse health condition) and all scores were \<=1.
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48 Weeks 36 and 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. DAS28-4 (ESR) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.70\*In(ESR in mm/hour) + 0.014\*PtGA in mm. Percentage of participants with DAS remission (DAS28-4-ESR\<2.6) were reported in this outcome measure.
Double Blind Phase: Percentage of Participants With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 36 and 48 Weeks 36 and 48 DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/l +1) + 0.014\*PtGA in mm+ 0.96. Percentage of participants with DAS remission (DAS28-4-CRP\<2.6) were reported in this outcome measure.
Double Blind Phase: Percentage of Participants With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48 Weeks 36 and 48 CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of \<=10 indicated low disease activity and a score of \<= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm).
Double Blind Phase: Percentage of Participants With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48 Weeks 36 and 48 SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm \[very well\] to 10 cm \[worst\]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of \<=11 indicates low disease activity and a score of \<=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL).
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48 Baseline (Day 1), Weeks 36 and 48 Participants with 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Weeks 36 and 48 Baseline (Day 1), Weeks 36 and 48 Participants with 50% improvement in tender and swollen joint counts and 50% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Double Blind Phase: Percentage of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Weeks 36 and 48 Baseline (Day 1), Weeks 36 and 48 Participants with 70% improvement in tender and swollen joint counts and 70% improvement in at least 3 of the 5 measures: PtGA, PhyGA, participant's assessment of arthritis pain, HAQ-DI and CRP. PtGA: participant assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged participants' pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Participant's assessment of arthritis pain: participant assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1).
Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized to derive the 2 component scores (physical component scores \[PCS\], mental component scores \[MCS\]) ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized aggregated to derive the two 2 component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition.
Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48 WPAI is 6-question participant rated questionnaire to determine the impact of rheumatoid arthritis and yields 4 types of outcomes: absenteeism (work time missed), presenteeism (impairment while working), work productivity loss (overall work impairment), and daily activity impairment (activity impairment) for a period of 7 days prior to a visit. These 4 outcomes are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. 3 possible answers for mobility: 1=no problem in walking, 2=moderate problems in walking, 3= confined to bed; self-care: 1=no problem, 2=moderate problems, 3= unable to wash/dress; usual activities: 1=no problem, 2=moderate problems, 3= unable to do usual activities; pain and discomfort: 1=no pain or discomfort, 2=moderate pain or discomfort, 3= extreme pain or discomfort; anxiety and depression: 1=not anxious or depressed, 2=moderately anxious or depressed, 3= extremely anxious or depressed. The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state.
Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Weeks 36 and 48 Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48 The FACIT-Fatigue scale was a participant completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (maximum fatigue) to 4 (no fatigue), higher scores indicate less fatigue. Total FACIT-fatigue score was obtained by addition of scores from 13 items, giving a possible overall range from 0 (maximum fatigue) to 52 (no fatigue). Higher FACIT-fatigue scores indicated lower level of fatigue, better participant status.
Double Blind Phase: Percentage of Participants Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48 Baseline (Day 1), Weeks 36 and 48 HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Percentage of participants with an improvement of at least 0.22 units in HAQ scores from baseline (Day 1) to Weeks 36 and 48 were reported in this outcome measure.
Trial Locations
- Locations (132)
Rheumatology Associates of North Alabama, PC
🇺🇸Huntsville, Alabama, United States
Arthrocare, Arthritiscare & Research, PC
🇺🇸Gilbert, Arizona, United States
SunValley Arthritis Center, Ltd.
🇺🇸Peoria, Arizona, United States
CHI St. Vincent Medical Group Hot Springs
🇺🇸Hot Springs, Arkansas, United States
Med Investigations, Inc
🇺🇸Fair Oaks, California, United States
HCP Clinical Research, LLC
🇺🇸Huntington Beach, California, United States
Sierra Rheumatology
🇺🇸Roseville, California, United States
Pacific Arthritis Center Medical Group
🇺🇸Santa Maria, California, United States
Robin K. Dore, MD, Inc.
🇺🇸Tustin, California, United States
Inland Rheumatology and Osteoporosis Medical Group
🇺🇸Upland, California, United States
Scroll for more (122 remaining)Rheumatology Associates of North Alabama, PC🇺🇸Huntsville, Alabama, United States