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A Study of PF-06438179 (Infliximab-Pfizer) and Infliximab in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (REFLECTIONS B537-02).

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02222493
Recruitment Status : Completed
First Posted : August 21, 2014
Results First Posted : September 11, 2017
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE August 19, 2014
First Posted Date  ICMJE August 21, 2014
Results First Submitted Date  ICMJE June 26, 2017
Results First Posted Date  ICMJE September 11, 2017
Last Update Posted Date May 30, 2018
Actual Study Start Date  ICMJE August 26, 2014
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2018)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14: Period 1 [ Time Frame: Week 14 ]
ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity (PGA); physician global assessment of disease activity; self-assessed disability (health assessment questionnaire-disability index [HAQ-DI]); and C-Reactive Protein (CRP).
Original Primary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
Number of Participants With an American College of Rheumatology 20% (ACR20) Response [ Time Frame: 14 Weeks ]
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2018)
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2, 4, 6, 12, 22 and 30 (Pre-dose): Period 1 [ Time Frame: Week 2, 4, 6, 12, 22 and 30 (pre-dose) ]
    ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 38, 46 and 54 (Pre-dose): Period 2 [ Time Frame: Week 38, 46 and 54 (pre-dose) ]
    ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 62, 70 and 78: Period 3 [ Time Frame: Week 62, 70 and 78 ]
    ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; HAQ-DI and CRP.
  • Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 2, 4, 6, 12, 14, 22 and 30 (Pre-dose): Period 1 [ Time Frame: Week 2, 4, 6, 12, 14, 22 and 30 (pre-dose) ]
    ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.
  • Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 38, 46 and 54 (Pre-dose): Period 2 [ Time Frame: Week 38, 46 and 54 (pre-dose) ]
    ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.
  • Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 62, 70 and 78: Period 3 [ Time Frame: Week 62, 70 and 78 ]
    ACR50 response: >=50% improvement in tender joint count, >=50% improvement in swollen joint count improvement and >=50% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP. ACR70 response: >=70% improvement in tender joint count, >=70% improvement in swollen joint count improvement and >=70% in at least 3 of 5 remaining ACR core measures: participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, HAQ-DI and CRP.
  • Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 2, 4, 6, 12, 14, 22 and 30: Period 1 [ Time Frame: Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30 ]
    DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on visual analogue scale [VAS] from 0 to 100 mm; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) less than (<)2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and greater than (>) 5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.
  • Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 38, 46 and 54: Period 2 [ Time Frame: Baseline (Week 30 pre-dose), Week 38, 46 and 54 ]
    DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on VAS from 0 to 100 millimeter [mm]; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) <2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and >5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.
  • Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 62, 70 and 78: Period 3 [ Time Frame: Baseline (Week 54 pre-dose), Week 62, 70 and 78 ]
    DAS28 is measure of disease activity in participants. DAS28-4 (CRP): calculated from SJC, TJC, CRP(mg/L) and PGA (participant rated disease activity on VAS from 0 to 100 mm; high score=worse health). Total score range of DAS28-4 (CRP): 0 to 9.4(0=no activity; 9.4=extreme disease activity), higher score=more disease activity. DAS28-4(CRP) <2.6=remission, <3.2=low disease activity, >=3.2-5.1=moderate disease activity and >5.1=high disease activity. HAQ-DI assess degree of difficulty a participant experienced (past week) in 8 domain of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each item scored on a 4-point scale ranging from 0 to 3(0=no difficulty; 3=extreme difficulty). Overall score: sum of domain scores/number of domains answered. Total possible score range (0=least difficulty; 3=extreme difficulty); high scores=more difficulty in performing daily living activities.
  • Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 1 [ Time Frame: Week 2, 4, 6, 12, 14, 22 and Week 30 (pre-dose) ]
    ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and patient's global assessment of arthritis (PGA) all were less than or equal to (=<) 1 or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.
  • Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 2 [ Time Frame: Week 38, 46 and 54 (pre-dose) ]
    ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and PGA all were =<1 or the score on the SDAI was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.
  • Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 3 [ Time Frame: Week 62, 70 and 78 ]
    ACR/EULAR remission was considered if the scores on tender joint count, swollen joint count, hs-CRP (mg/dL), and PGA all were =<1 or the score on the SDAI was =<3.3. SDAI was calculated as the sum of number of tender and swollen joint count (using 28 joints), PGA, physician global assessment, and CRP (mg/dL). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. Physician global assessment was recorded on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicated more disease activity. DAS28 calculated from number of swollen joints and painful joints using the 28 joints count, CRP (mg/dL) and PGA using a 10 mm-VAS from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition. DAS28 <3.2: low disease activity, DAS28 <2.6: remission.
  • Number of Participants With European League Against Rheumatism (EULAR) Response: Period 1 [ Time Frame: Week 2, 4, 6, 12, 14, 22 and Week 30 (pre-dose) ]
    EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.
  • Number of Participants With European League Against Rheumatism (EULAR) Response: Period 2 [ Time Frame: Week 38, 46 and Week 54 (pre-dose) ]
    EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.
  • Number of Participants With European League Against Rheumatism (EULAR) Response: Period 3 [ Time Frame: Week 62, 70 and Week 78 ]
    EULAR response was based on DAS28 EULAR response criteria which was defined as good response = DAS28 change of >1.2 with DAS28 =<3.2; moderate response = DAS28 change of >0.6 to =<1.2 with DAS28 >3.2-5.1 and no-response = DAS28 change of =<0.6 with DAS28 >5.1.
  • 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 30 ]
    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 were events between first dose of study drug and up to Week 30 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2 [ Time Frame: Baseline (Week 30 pre-dose) up to Week 54 ]
    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 were events between first dose of study drug and up to Week 54 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3 [ Time Frame: Baseline (Week 54 pre-dose) up to Week 78 ]
    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 were events between first dose of study drug and up to Week 78 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 in a participant who received study drug. AEs included both serious and non-serious adverse events.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 1 [ Time Frame: Baseline (Day 1) up to Week 30 ]
    AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 2 [ Time Frame: Baseline (Week 30 pre-dose) up to Week 54 ]
    AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) of Grade 3 or Higher Severity: Period 3 [ Time Frame: Baseline (Week 54 pre-dose) up to Week 78 ]
    AEs were graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Version 4.03 as Grades 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life threatening AEs and Grade 5= death related to AE. AEs of Grade 3 and higher severity are reported in this outcome measure.
  • Number of Participants With Laboratory Abnormalities: Period 1 [ Time Frame: Baseline (Day 1) up to Week 30 ]
    Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN; renal function:blood urea nitrogen,creatinine: >1.3*ULN; uric acid: >1.2*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: <0.9*LLN,>1.1*ULN; urinalysis: pH<4.5, >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: <0.6*LLN,>1.5*ULN). Participants with any laboratory abnormality in Period 1 were reported in this outcome measure.
  • Number of Participants With Laboratory Abnormalities: Period 2 [ Time Frame: Baseline (Week 30 pre-dose) up to Week 54 ]
    Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN; renal function:blood urea nitrogen,creatinine: >1.3*ULN; uric acid: >1.2*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: <0.9*LLN,>1.1*ULN; urinalysis: pH<4.5, >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: <0.6*LLN,>1.5*ULN). Participants with any laboratory abnormality in Period 2 were reported in this outcome measure.
  • Number of Participants With Laboratory Abnormalities: Period 3 [ Time Frame: Baseline (Week 54 pre-dose) up to Week 78 ]
    Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); platelets: >1.75*upper limit of normal (ULN); white blood cell count: <0.6*LLN; basophils, eosinophils, monocytes: >1.2*ULN. liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN; renal function:blood urea nitrogen,creatinine: >1.3*ULN; uric acid: >1.2*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: <0.9*LLN,>1.1*ULN; urinalysis: pH<4.5, >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: <0.6*LLN,>1.5*ULN). Participants with any laboratory abnormality in Period 3 were reported in this outcome measure.
  • Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 2, 4, 6, 12, 14, 22 and 30: Period 1 [ Time Frame: Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and Week 30 ]
    Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.
  • Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 38, 46 and 54: Period 2 [ Time Frame: Baseline (Week 30 pre-dose), Week 38, 46 and Week 54 ]
    Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.
  • Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 62, 70 and 78: Period 3 [ Time Frame: Baseline (Week 54 pre-dose), Week 62, 70 and 78 ]
    Tender joint count was an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed as: Present or Absent. Swollen joint count was an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling as: Present or Absent.
  • Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 2, 4, 6, 12, 14, 22, 30: Period 1 [ Time Frame: Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30 ]
    PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.
  • Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 38, 46 and 54: Period 2 [ Time Frame: Baseline (Week 30 pre-dose), Week 38, 46 and 54 ]
    PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.
  • Change From Baseline in Patient's Assessment of Arthritis Pain (PAAP), Patient's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 62, 70 and 78: Period 3 [ Time Frame: Baseline (Week 54 pre-dose), Week 62, 70 and 78 ]
    PAAP: Participants assessed the severity of their arthritis pain by using a 100 mm VAS ranging from 0 (no pain) to 100 (most severe pain), which corresponded to the magnitude of their pain, where higher scores indicated more pain. PGA: Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" and their response was recorded on a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated worse health condition. PGAA: Participants were assessed how their overall arthritis appears at the time of the visit. The evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the PAAP and PGA assessments. The physician's response was recorded using a 100 mm VAS ranging from 0 (very well) to 100 (very poor), where higher scores indicated more disease activity.
  • Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 2, 4, 6, 12, 14, 22 and 30: Period 1 [ Time Frame: Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30 ]
  • Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 38, 46 and 54: Period 2 [ Time Frame: Baseline (Week 30 pre-dose), Week 38, 46 and 54 ]
  • Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 62, 70 and 78: Period 3 [ Time Frame: Baseline (Week 54 pre-dose), Week 62, 70 and 78 ]
  • Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 1 [ Time Frame: Baseline (Day 1) up to Week 30 ]
    ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.
  • Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 2 [ Time Frame: Baseline (Week 30 pre-dose) up to Week 54 ]
    ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.
  • Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 3 [ Time Frame: Baseline (Week 54 pre-dose) up to Week 78 ]
    ADA positive results was defined as ADA titer level >=1.30 and NAb positive was defined as NAb titer level >=0.70.
  • Serum Concentration Versus Time Summary: Period 1 [ Time Frame: Pre dose on Day 1, 15, 43, 99, 155 and 211; 2 hours post dose on Day 1 and 99; and 336 hours post dose on Day 29 ]
  • Serum Concentration Versus Time Summary: Period 2 [ Time Frame: Pre dose on Day 211, 267, 379 and 547 ]
  • Serum Concentration Versus Time Summary: Period 3 [ Time Frame: Pre dose on Day 379, 435 and 547 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response [ Time Frame: 30 Weeks ]
    ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).
  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: 30 Weeks ]
    ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: 30 Weeks ]
    ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
  • Disease Activity Score Based on 28-joints Count (DAS28)-CRP [ Time Frame: 30 Weeks ]
  • DAS Remission [ Time Frame: 30 Weeks ]
  • EULAR Response [ Time Frame: 30 Weeks ]
  • Change from baseline in individual components of ACR response [ Time Frame: 30 Weeks ]
  • Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) in response to infliximab-Pfizer and infliximab-EU [ Time Frame: 30 Weeks ]
  • Serum drug concentration [ Time Frame: 30 Weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PF-06438179 (Infliximab-Pfizer) and Infliximab in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (REFLECTIONS B537-02).
Official Title  ICMJE A Phase 3 Randomized, Double-blind Study Assessing The Efficacy And Safety Of Pf-06438179 And Infliximab In Combination With Methotrexate In Subjects With Moderately To Severely Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate
Brief Summary The study will assess the efficacy and safety of PF-06438179 and infliximab in combination with methotrexate in subjects with active rheumatoid arthritis who have had an inadequate response to methotrexate.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Biological: PF-06438179
    PF-06438179 will be administered by intravenous infusion at an initial dose of 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.
    Other Name: Infliximab-Pfizer
  • Biological: Infliximab
    Infliximab will be administered by intravenous infusion at an initial dose of 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.
    Other Name: Infliximab-EU, Remicade
Study Arms  ICMJE
  • Experimental: PF-06438179
    Intervention: Biological: PF-06438179
  • Active Comparator: Infliximab
    Intervention: Biological: Infliximab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2016)
650
Original Estimated Enrollment  ICMJE
 (submitted: August 19, 2014)
614
Actual Study Completion Date  ICMJE June 1, 2017
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 10 mg/L.

Must have received methotrexate for at least 12 weeks and be on a stable dose for at least 4 weeks.

Exclusion Criteria:

Evidence of untreated or inadequately treated latent or active TB.

Evidence or history of moderate or severe heart failure (NYHA Class III/IV)

Infection requiring hospitalization or parenteral antimicrobial therapy judged clinically significant by the investigator within 6 months prior to first dose of study drug.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Czechia,   Georgia,   Germany,   Guatemala,   Hungary,   Israel,   Japan,   Jordan,   Korea, Republic of,   Lithuania,   Mexico,   Morocco,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   Serbia,   South Africa,   Tunisia,   Ukraine,   United Kingdom,   United States
Removed Location Countries Colombia,   Czech Republic,   France
 
Administrative Information
NCT Number  ICMJE NCT02222493
Other Study ID Numbers  ICMJE B5371002
REFLECTIONS B537-02 ( Other Identifier: Alias ID )
2013-004148-49 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP