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A Study Of PF-06410293 (Adalimumab-Pfizer) And Adalimumab (Humira®) In Combination With Methotrexate In Subjects With Active Rheumatoid Arthritis (REFLECTIONS B538-02).

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ClinicalTrials.gov Identifier: NCT02480153
Recruitment Status : Completed
First Posted : June 24, 2015
Results First Posted : September 26, 2017
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: PF-06410293 Biological: Adalimumab Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 597 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY ASSESSING THE EFFICACY AND SAFETY OF PF-06410293 AND ADALIMUMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE
Actual Study Start Date : June 25, 2015
Actual Primary Completion Date : August 31, 2016
Actual Study Completion Date : December 6, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06410293 Biological: PF-06410293
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.
Other Name: Adalimumab-Pfizer

Active Comparator: Adalimumab Biological: Adalimumab
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.
Other Name: Adalimumab-European Union, Humira®




Primary Outcome Measures :
  1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1 [ Time Frame: Week 12 ]
    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).


Secondary Outcome Measures :
  1. Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1 [ Time Frame: Weeks 2, 4, 6, 8, 18 and 26 (pre-dose) ]
    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).

  2. Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  3. Number of Participants With an American College of Rheumatology 20% (ACR20) Response: Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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).

  4. Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 1 [ Time Frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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).

  5. Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  6. Number of Participants With an American College of Rheumatology 50% (ACR50) Response: Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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).

  7. Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 1 [ Time Frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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).

  8. Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  9. Number of Participants With an American College of Rheumatology 70% (ACR70) Response: Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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).

  10. Change From Baseline in Tender Joint Count: Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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).

  11. Change From Baseline in Tender Joint Count: Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  12. Change From Baseline in Tender Joint Count: Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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).

  13. Change From Baseline in Swollen Joint Count: Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.

  14. Change From Baseline in Swollen Joint Count: Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.

  15. Change From Baseline in Swollen Joint Count: Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints.

  16. Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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".

  17. Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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".

  18. Change From Baseline in Physician's Global Assessment of Arthritis (PGAA): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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".

  19. Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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.

  20. Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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.

  21. Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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.

  22. Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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".

  23. Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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".

  24. Change From Baseline in Patient's Global Assessment of Arthritis (PGA): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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".

  25. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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.

  26. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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.

  27. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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.

  28. Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 1 [ Time Frame: Baseline, Weeks1, 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.

  29. Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.

  30. Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant.

  31. Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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).

  32. Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2 [ Time Frame: Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  33. Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3 [ Time Frame: Baseline, Weeks 52, 56, 66, 76 and 78 ]
    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).

  34. Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 1 [ Time Frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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.

  35. Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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.

  36. Number of Participants Achieving European League Against Rheumatism (EULAR) Response: Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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.

  37. Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 1 [ Time Frame: Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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.

  38. Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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.

  39. Number of Participants Achieving Disease Activity Score Remission (DAS <2.6): Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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.

  40. Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response:Period 1 [ Time Frame: Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose) ]
    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).

  41. Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2 [ Time Frame: Weeks 26, 30, 36, 44 and 52 (pre-dose) ]
    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).

  42. Number of Participants Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3 [ Time Frame: Weeks 52, 56, 66, 76 and 78 ]
    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).

  43. 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 ]
  44. Serum Concentration Versus Time Summary: Period 2 [ Time Frame: Pre-dose on Days 183, 211, 253 and 365 ]
  45. Serum Concentration Versus Time Summary: Period 3 [ Time Frame: Pre-dose on Days 365, 393, 463, 547 and 575 ]
  46. Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1 [ Time Frame: Baseline up to Week 26 (pre-dose) ]
    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.

  47. Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2 [ Time Frame: Week 26 dosing up to Week 52 (pre-dose) ]
    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.

  48. Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3 [ Time Frame: Week 52 dosing up to follow-up visit (Week 92) ]
    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.

  49. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1 [ Time Frame: Baseline (Day 1) up to Week 26 (pre-dose) ]
    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.

  50. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2 [ Time Frame: Week 26 dosing up to Week 52 (pre-dose) ]
    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.

  51. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3 [ Time Frame: Week 52 dosing up to follow-up visit (Week 92) ]
    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.

  52. Number of Participants With Laboratory Abnormalities: Period 1 [ Time Frame: Baseline (Day 1) up to Week 26 (pre-dose) ]
    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.

  53. Number of Participants With Laboratory Abnormalities: Period 2 [ Time Frame: Week 26 dosing up to Week 52 (pre-dose) ]
    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.

  54. Number of Participants With Laboratory Abnormalities: Period 3 [ Time Frame: Week 52 dosing up to follow-up visit (Week 92) ]
    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.


Other Outcome Measures:
  1. Percentage of Participants Who Achieved Delivery Success in Sub-study [ Time Frame: Weeks 56, 58, 60, 62, 64, 66 ]
    A sub-study was conducted to determine whether participants or their non-healthcare professional caregivers could safely and effectively administer PF-06410293 with the sponsor's prefilled pen (PFP) device.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of rheumatoid arthritis based on 2010 ACR/EULAR criteria for at least 4 months.
  • At least 6 tender (of 68 assessed) and 6 swollen (of 66 assessed) joints at screening and baseline.
  • Hs-CRP equal or greater than 8 mg/L.
  • Must have received methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to the first study dose.

Exclusion Criteria:

  • Evidence of untreated or inadequately treated latent or active TB.
  • Evidence of uncontrolled, clinically significant diseases, including moderate or severe heart failure (NYHA Class III/IV) or malignancy in the previous 5 years.
  • History of infection requiring hospitalization or parenteral antimicrobial therapy within 6 months prior to first dose of study drug.
  • May have received no more than 2 doses of one biologic therapy (other than adalimumab or lymphocyte depleting therapy).
  • Any second DMARD must be washed out prior to the first study dose.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02480153


  Show 183 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02480153     History of Changes
Other Study ID Numbers: B5381002
B5381002, REFLECTIONS B538-02
2014-000352-29 ( EudraCT Number )
ADALIMUMAB ( Other Identifier: Alias Study Number )
First Posted: June 24, 2015    Key Record Dates
Results First Posted: September 26, 2017
Last Update Posted: January 23, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
Phase 3
adalimumab
rheumatoid arthritis
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents