The study will assess the efficacy, safety, and immunogenicity of PF-06410293 and adalimumab in combination with methotrexate in subjects with moderately to severly active rheumatoid arthritis who have had an inadequate response to methotrexate. In an additional optional portion of the study, during open label Treatment Period 3 (TP3), a subset of subjects used a Prefilled Pen (PFP) to administer up to 3 injections of their study treatment (PF-06410293) at home.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
597
PF-06410293 will be administered with a uniform dose regimen, which is SC injection at a dose of 40 mg every other week, throughout the study treatment.
Adalimumab will be administered with a uniform dose regimen, which is SC injection at a dose of 40 mg every other week, throughout the study treatment.
ArthroCare, Arthritis Care & Research P.C.
Gilbert, Arizona, United States
Arizona Arthritis & Rheumatology Associates, PC
Glendale, Arizona, United States
Arizona Arthritis & Rheumatology Associates, PC
Phoenix, Arizona, United States
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
Fullerton, California, United States
East Bay Rheumatology Medical Group, Inc.
San Leandro, California, United States
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1
ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Week 12
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1
ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 2, 4, 6, 8, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 2
ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 3
ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 52, 56, 66, 76 and 78
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 1
ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 2
ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 3
ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 52, 56, 66, 76 and 78
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 1
ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 2
ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 3
ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI).
Time frame: Weeks 52, 56, 66, 76 and 78
Change From Baseline in Tender Joint Count: Period 1
Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Tender Joint Count: Period 2
Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Tender Joint Count: Period 3
Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V).
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Swollen Joint Count: Period 1
Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Swollen Joint Count: Period 2
Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Swollen Joint Count: Period 3
Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 1
The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 2
The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 3
The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This was an evaluation based on the participant's disease symptoms, functional capacity and physical examination, and independent of the participant's reported assessments of PGA (patient's global assessment of arthritis) and PAAP (patient's assessment of arthritis pain). The investigator's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "None" and the 100 mm end labeled "Extreme".
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 1
Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 2
Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 3
Participants assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 1
Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 2
Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 3
Participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participant's response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled "Very Well" and the 100 mm end labeled "Very Poorly".
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1
HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2
HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3
HAQ-DI assesses the degree of difficulty a participant had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each activity category consisted of 2-3 items. For each question in the questionnaire, the level of difficulty was scored from 0 to 3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Any activity that required assistance from another individual or required the use of an assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 representing "no difficulty", 1 as "some difficulty", 2 as "much difficulty", and 3 as "unable to do". Higher score indicate more difficulty in performing daily living activities.
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 1
Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Time frame: Baseline, Weeks1, 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 2
Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 3
Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Time frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).
Time frame: Baseline, Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 1
EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Time frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 2
EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 3
EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline \>1.2 and DAS28 =\<3.2. Moderate response was achieved if DAS28 improvement from baseline \>0.6 to =\<1.2 and DAS28 =\<5.1; or DAS improvement from baseline \>1.2 and DAS28 \>3.2. No response was achieved if DAS improvement from baseline =\<0.6 (no matter present DAS28 score); or DAS improvement from baseline \>0.6 to =\<1.2 and DAS28 \>5.1.
Time frame: Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 1
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 2
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 3
The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient's global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP \[mg/L\] +1) + 0.014 (PGA \[mm\]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) \<2.6 indicates remission.
Time frame: Weeks 52, 56, 66, 76 and 78
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response：Period 1
Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Time frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2
Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Time frame: Weeks 26, 30, 36, 44 and 52 (pre-dose)
Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3
Participants were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =\<1; or the score on the simplified disease activity index (SDAI) was =\<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician's global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL).
Time frame: Weeks 52, 56, 66, 76 and 78
Serum Concentration Versus Time Summary: Period 1
Time frame: Pre-dose on Days 1, 15, 43, 85 and 183, and at any time during Day 8 visit
Serum Concentration Versus Time Summary: Period 2
Time frame: Pre-dose on Days 183, 211, 253 and 365
Serum Concentration Versus Time Summary: Period 3
Time frame: Pre-dose on Days 365, 393, 463, 547 and 575
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1
Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Time frame: Baseline up to Week 26 (pre-dose)
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2
Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Time frame: Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3
Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer \>=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer \>=0.70.
Time frame: Week 52 dosing up to follow-up visit (Week 92)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 1 were events between first dose of study drug in Period 1 and up to Week 26 pre-dose assessments that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Time frame: Baseline (Day 1) up to Week 26 (pre-dose)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 2 were events between first dose of study drug in Period 2 and up to Week 52 pre-dose assessments that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Time frame: Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs for Period 3 were events between first dose of study drug in Period 3 and up to Week 92 visit that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs.
Time frame: Week 52 dosing up to follow-up visit (Week 92)
Number of Participants With Laboratory Abnormalities: Period 1
Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 1 (without regard to baseline abnormality) is presented.
Time frame: Baseline (Day 1) up to Week 26 (pre-dose)
Number of Participants With Laboratory Abnormalities: Period 2
Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 2 (without regard to baseline abnormality) is presented.
Time frame: Week 26 dosing up to Week 52 (pre-dose)
Number of Participants With Laboratory Abnormalities: Period 3
Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of participants with any laboratory abnormality during Period 3 (without regard to baseline abnormality) is presented.
Time frame: Week 52 dosing up to follow-up visit (Week 92)
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Westlake Medical Research
Thousand Oaks, California, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, United States
Desert Valley Medical Group
Victorville, California, United States
Javed Rheumatology Associates, Inc
Newark, Delaware, United States
Arthritis and Rheumatic Disease Specialties
Aventura, Florida, United States
...and 173 more locations