MedPath

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

Phase 3
Completed
Conditions
Rheumatoid Arthritis
Interventions
Biological: Infliximab
Biological: PF-06438179
Registration Number
NCT02222493
Lead Sponsor
Pfizer
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
650
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InfliximabInfliximab-
PF-06438179PF-06438179-
Primary Outcome Measures
NameTimeMethod
Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14: Period 1Week 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).

Secondary Outcome Measures
NameTimeMethod
Number of Participants With an American College of Rheumatology 50% (ACR50) and ACR 70% Response at Week 62, 70 and 78: Period 3Week 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.

Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2, 4, 6, 12, 22 and 30 (Pre-dose): Period 1Week 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 2Week 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 3Week 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 1Week 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 2Week 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.

Change From Baseline in Disease Activity Score-CRP (4 Variables) (DAS28-4 [CRP]) and HAQ-DI at Week 62, 70 and 78: Period 3Baseline (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 1Week 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.

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 1Baseline (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 2Baseline (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.

Number of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and Disease Activity Score (DAS <2.6) Remission: Period 2Week 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 3Week 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 1Week 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 2Week 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 3Week 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 1Baseline (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 2Baseline (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 3Baseline (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 1Baseline (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 2Baseline (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 3Baseline (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 1Baseline (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 2Baseline (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 3Baseline (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 1Baseline (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 2Baseline (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 3Baseline (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 High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 38, 46 and 54: Period 2Baseline (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 3Baseline (Week 54 pre-dose), Week 62, 70 and 78
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Status: Period 1Baseline (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 2Baseline (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 3Baseline (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 1Pre 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 2Pre dose on Day 211, 267, 379 and 547
Serum Concentration Versus Time Summary: Period 3Pre dose on Day 379, 435 and 547
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 1Baseline (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 2Baseline (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 3Baseline (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 1Baseline (Day 1), Week 2, 4, 6, 12, 14, 22 and 30

Trial Locations

Locations (183)

Rabta Hospital

🇹🇳

Tunis, Tunisia

Regional Medical Clinic

🇺🇸

Rapid City, South Dakota, United States

LTD Tbilisi Central Hospital

🇬🇪

Tbilisi, Georgia

LTD Medulla" Chemotherapy and Immunotherapy Clinic

🇬🇪

Tbilisi, Georgia

National Hospital Organization Sagamihara National Hospital

🇯🇵

Sagamihara, Kanagawa, Japan

Low Country Rheumatology, PA

🇺🇸

Charleston, South Carolina, United States

General Hospital "Prim.dr.Abdulah Nakas"

🇧🇦

Sarajevo, Kanton Sarajevo, Bosnia and Herzegovina

University Clinical Center Tuzla

🇧🇦

Tuzla, Tuzlanski Kanton, Bosnia and Herzegovina

Ramesh C Gupta, MD

🇺🇸

Memphis, Tennessee, United States

Clinical Center University of Sarajevo

🇧🇦

Sarajevo, Kanton Sarajevo, Bosnia and Herzegovina

University Multiprofile Hospital for Active Treatment (UMHAT) "Kaspela" EOOD

🇧🇬

Plovdiv, Bulgaria

Tbilisi Heart and Vascular Clinic LTD

🇬🇪

Tbilisi, Georgia

LTD MediClubGeorgia

🇬🇪

Tbilisi, Georgia

LTD Adapti

🇬🇪

Tbilisi, Georgia

DRC Gyógyszervizsgáló Központ Kft.

🇭🇺

Balatonfüred, Hungary

Sasebo Chuo Hospital

🇯🇵

Sasebo, Nagasaki, Japan

Kurashiki Sweet Hospital

🇯🇵

Kurashiki, Okayama, Japan

Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem

🇮🇱

Jerusalem, Israel

Inoue Hospital

🇯🇵

Takasaki, Gunma, Japan

Mazda Hospital

🇯🇵

Aki-gun, Hiroshima, Japan

Sapporo City General Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Hokkaido University Hospital

🇯🇵

Sapporo, Hokkaido, Japan

National Hospital Organization Nagasaki Medical Center

🇯🇵

Omura, Nagasaki, Japan

Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.

🇲🇽

San Luis De Potosí, SAN LUIS DE Potosi, Mexico

Yokohama Minami Kyosai Hospital

🇯🇵

Yokohama, Kanagawa, Japan

Centro de diagnóstico por imágenes, Radiología General y Especial

🇵🇪

Arequipa, Peru

Unidad de Investigación en Medicina Interna y Enfermedades Críticas

🇵🇪

Arequipa, Peru

Centro de Investigación Reumatología CAA

🇵🇪

Lima, Peru

Instituto de Ginecología y Reproducción & Cirugía Mínimamente Invasiva

🇵🇪

Santiago de Surco, Lima, Peru

Yuaikai Tomishiro Central Hospital

🇯🇵

Tomigusuku, Okinawa, Japan

Saitama Medical Center

🇯🇵

Kawagoe-shi, Saitama, Japan

Hirose Clinic

🇯🇵

Tokorozawa-shi, Saitama, Japan

National Hospital Organization Shizuoka Medical Center

🇯🇵

Sunto-gun, Shizuoka, Japan

St. Luke's International Hospital

🇯🇵

Chuo-ku, Tokyo, Japan

National Hospital Organization Chiba-East Hospital

🇯🇵

Chiba, Japan

Kondo clinic for rheumatism and orthopaedics

🇯🇵

Fukuoka, Japan

Toho University Ohashi Medical Center

🇯🇵

Meguro-ku, Tokyo, Japan

Showa University Hospital

🇯🇵

Shinagawa-ku, Tokyo, Japan

National Hospital Organization Kyushu Medical Center

🇯🇵

Fukuoka, Japan

Unidad de Investigaciones Reumatológicas A.C - Hospital Central "Dr. Ignacio Morones Prieto"

🇲🇽

Zona Universitaria, SAN LUIS DE Potosi, Mexico

El Ayachi Hospital

🇲🇦

Salé, Morocco

Clinica Medica Cayetano Heredia

🇵🇪

Lima, Peru

Servicio de Inmunología y Reumatología

🇵🇪

Lima, Peru

Medical Center Manila

🇵🇭

Manila, Philippines

Twoja Przychodnia - Centrum Medyczne Nowa Sol

🇵🇱

Nowa Sol, Poland

GBUZ of city of Moscow

🇷🇺

Moscow, Russian Federation

Komunalnyi zaklad Sumskoi oblasnoi rady "Sumska oblasna klinichna likarnia"

🇺🇦

M. Sumy, Ukraine

Advance Medical Research Services Corporation

🇺🇸

Miami, Florida, United States

Accurate Clinical Research, Inc.

🇺🇸

Houston, Texas, United States

Desert Valley Medical Group

🇺🇸

Victorville, California, United States

Alastair C. Kennedy, MD

🇺🇸

Vero Beach, Florida, United States

Sarasota Arthritis Research Center

🇺🇸

Sarasota, Florida, United States

Graves-Gilbert Clinic Bowling Green

🇺🇸

Bowling Green, Kentucky, United States

Clinical Research Center of Reading, LLC

🇺🇸

Wyomissing, Pennsylvania, United States

Austin Regional Clinic

🇺🇸

Austin, Texas, United States

CETI - Centro de Estudos em Terapias Inovadoras

🇧🇷

Curitiba, Paraná, Brazil

Clinical Research and Arthritis Center

🇨🇦

Windsor, Ontario, Canada

Elisabeth-Klinik gGmbH

🇩🇪

Olsberg, Germany

Clínica Médica especializada en Medicina Interna

🇬🇹

Guatemala, Guatemala

Qualiclinic Kft.

🇭🇺

Budapest, Hungary

Anjo Kosei Hospital

🇯🇵

Anjo-shi, Aichi, Japan

Meir Medical Center

🇮🇱

Kfar Saba, Israel

Aso Iizuka Hospital

🇯🇵

Iiduka, Fukuoka, Japan

Hospital María Auxiliadora - Centro de Investigaciones Medicas

🇵🇪

San juan de Miraflores, Lima, Peru

Groupe Radiologique de Salé

🇲🇦

Salé, Morocco

Laboratoire les Arcades d'Analyses Médicales

🇲🇦

Salé, Morocco

Mary Mediatrix Medical Center

🇵🇭

Lipa City, Batangas, Philippines

Philippine General Hospital

🇵🇭

Manila, Philippines

Spitalul Clinic Judetean de Urgenta Galati "Sf. Apostol Andrei"

🇷🇴

Galati, Romania

MTZ Clinical Research Sp. z o.o.

🇵🇱

Warszawa, Poland

Spitalul Clinic Judetean de Urgenta Targu Mures

🇷🇴

Targu Mures, Romania

GAUZ of Kemerovo Region "Regional clinical hospital for war veterans"

🇷🇺

Kemerovo, Russian Federation

KGBUZ "Krasnoyarsk Interdistrict Clinical Hospital #20 n.a. I.S.Berzon"

🇷🇺

Krasnoyarsk, Russian Federation

GBUZ "Republican hospital n.a. V.A.Baranov"

🇷🇺

Petrozavodsk, Republic OF Karelia, Russian Federation

GBOU VPO "Ryazan State medical university n.a. academician I.P.Pavlov"

🇷🇺

Ryazan, Russian Federation

GMU " Kursk regional clinical hospital" of the Committee of Healthcare of the Kursk region

🇷🇺

Kursk, Russian Federation

Krasnoyarsk State Medical University n.a.Prof.V.F.Voyno-Yasenetsky

🇷🇺

Krasnoyarsk, Russian Federation

GBOUVPO "Ryazan State Medical University n.a. Academician I.P.Pavlov"

🇷🇺

Ryazan, Russian Federation

GBOU of Ryazan region "Regional clinical hospital"

🇷🇺

Ryazan, Russian Federation

GBU of Ryazan region "Regional clinical cardiology dispanser"

🇷🇺

Ryazan, Russian Federation

Spb GBUZ "Clinical rheumatology hospital # 25" City CDC prevention of osteoporosis

🇷🇺

Saint-Petersburg, Russian Federation

GUZ "Regional clinical hospital"

🇷🇺

Saratov, Russian Federation

Charlotte Maxeke Johannesburg Academic Hospital

🇿🇦

Johannesburg, Gauteng, South Africa

GBUZ VO 'Regional clinical hospital"

🇷🇺

Vladimir, Russian Federation

GBKUZ of Yaroslavl region "City hospital n. a. N.A. Semashko"

🇷🇺

Yaroslavl, Russian Federation

Institute for Treatment and Rehabilitation "Niska Banja"

🇷🇸

Niska Banja, Serbia

Emmed Research

🇿🇦

Pretoria, Gauteng, South Africa

Arthritis Clinical Research Unit

🇿🇦

Cape Town, Western CAPE, South Africa

Vincent Pallotti Hospital

🇿🇦

Cape Town, Western CAPE, South Africa

Derzhavna ustanova "Ukrainskyi derzhavnyi naukovo-doslidnyi instytut

🇺🇦

Dnipropetrovsk, Ukraine

Oblasna klinichna likarnia, revmatolohichne viddilennia, Derzhavnyi vyshchyi navchalnyi zaklad

🇺🇦

Ivano-Frankivsk, Ukraine

Komunalnyi zaklad okhorony zdorovia "Kharkivska miska klinichna likarnia #8"

🇺🇦

Kharkiv, Ukraine

Klinichnyi hospital Derzhavnoi prykordonnoi sluzhby Ukrainy

🇺🇦

Lviv, Ukraine

Khmelnytska oblasna likarnia

🇺🇦

Khmelnytskyi, Ukraine

Komunalnyi zaklad "Kryvorizka miska klinichna likarnia #2" Dnipropetrovskoi oblasnoi rady"

🇺🇦

M. Kryvyi Rih, Ukraine

Vinnytska oblasna klinichna likarnia im. M.I.Pyrohova, revmatolohichne

🇺🇦

M. Vinnytsia, Ukraine

Komunalna ustanova "Odeska oblasna klinichna likarnia"

🇺🇦

Odesa, Ukraine

R.K. Will Pty Ltd

🇦🇺

Victoria Park, Western Australia, Australia

Arizona Arthritis & Rheumatology Associates, P.C.

🇺🇸

Phoenix, Arizona, United States

Arthritis & Osteoporosis Medical Center

🇺🇸

La Palma, California, United States

Lekarna U Robina, s.r.o.

🇨🇿

Praha, Czechia

Achieve Clinical Research, LLC

🇺🇸

Birmingham, Alabama, United States

Inland Rheumatology Clinical Trials, Inc.

🇺🇸

Upland, California, United States

Harbin Clinic

🇺🇸

Rome, Georgia, United States

Arthritis and Rheumatic Disease Specialties

🇺🇸

Aventura, Florida, United States

Clinical and Translational Research Center of Alabama, PC

🇺🇸

Tuscaloosa, Alabama, United States

Sun Valley Arthritis Center, Ltd.

🇺🇸

Peoria, Arizona, United States

Javed Rheumatology Associates, Inc

🇺🇸

Newark, Delaware, United States

International Medical Research

🇺🇸

Daytona Beach, Florida, United States

St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare

🇺🇸

Fullerton, California, United States

Arthritis, Rheumatic & Back Disease Associates

🇺🇸

Voorhees, New Jersey, United States

San Marcus Research Clinic, Inc.

🇺🇸

Miami, Florida, United States

Indian River Primary Care

🇺🇸

Vero Beach, Florida, United States

Physician's Clinic of Iowa, P.C.

🇺🇸

Cedar Rapids, Iowa, United States

West Tennessee Research Institute

🇺🇸

Jackson, Tennessee, United States

Gilbert-Graves Clinic

🇺🇸

Bowling Green, Kentucky, United States

Ochsner Clinic Baton Rouge

🇺🇸

Baton Rouge, Louisiana, United States

Advanced Clinical Research

🇺🇸

Meridian, Idaho, United States

Arthritis and Diabetes Clinic, Inc.

🇺🇸

Monroe, Louisiana, United States

Trinity Health Center-Medical Arts

🇺🇸

Minot, North Dakota, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Regional Health Clinical Research

🇺🇸

Rapid City, South Dakota, United States

The Queen Elizabeth Hospital

🇦🇺

Woodville South, South Australia, Australia

The Center for Rheumatology and Bone Research

🇺🇸

Wheaton, Maryland, United States

University Hospital Clinical Center Banja Luka

🇧🇦

Banja Luka, Bosnia and Herzegovina

Metroplex Clinical Research Center

🇺🇸

Dallas, Texas, United States

Pharmacy Services, Sentara Leigh Hospital

🇺🇸

Norfolk, Virginia, United States

Sentara Medical Group, Clinical Research

🇺🇸

Norfolk, Virginia, United States

Gold Coast Private Hospital Pty Ltd

🇦🇺

Southport, Queensland, Australia

HPS Pharmacies

🇦🇺

Southport, Queensland, Australia

Paradise Arthritis and Rheumatology Pty Ltd

🇦🇺

Southport, Queensland, Australia

CliniPath Pathology

🇦🇺

Osborne Park, Western Australia, Australia

Lekarna Hradebni s.r.o.

🇨🇿

Uherske Hradiste, Czechia

CCBR-SYNARC a.s.

🇨🇿

Pardubice, Czechia

Multiprofile Hospital for Active Treatment Trimontium OOD

🇧🇬

Plovdiv, Bulgaria

CCBR Czech Brno, s.r.o.

🇨🇿

Brno, Czechia

Hospital Israelita Albert Einstein

🇧🇷

São Paulo, Brazil

University Multiprofile Hospital for Active Treatment (UMHAT) "Sv. Ivan Rilski" EAD

🇧🇬

Sofia, Bulgaria

MEDICAL PLUS, s.r.o.

🇨🇿

Uherske Hradiste, Czechia

BENU Lekarna

🇨🇿

Pardubice, Czechia

LTD Unimedi Kakheti

🇬🇪

Tbilisi, Georgia

Lekarna Lancier, s.r.o.

🇨🇿

Brno, Czechia

CCBR Czech Prague, s.r.o.

🇨🇿

Praha 3, Czechia

Schlosspark-Klinik

🇩🇪

Berlin, Germany

Knappschaftsklinikum Saar GmbH

🇩🇪

Puettlingen, Germany

Klinikum der Universität München

🇩🇪

München, Germany

Clínica Médica Especializada en Medicina Interna y Reumatología

🇬🇹

Guatemala, Guatemala

Rheumazentrum Ratingen

🇩🇪

Ratingen, Germany

Centro de Nutricion y Rehabilitacion Cardiorespiratoria, S.A. (NUCARE)

🇬🇹

Guatemala, Guatemala

Therapeutic Research Institute and Lab S.A

🇬🇹

Guatemala, Guatemala

Rambam Health Care Campus

🇮🇱

Haifa, Israel

Matsubara Mayflower Hospital

🇯🇵

Katoh, Hyogo, Japan

Kumamoto Orthopaedic Hospital

🇯🇵

Kumamoto, Japan

Jordan Hospital

🇯🇴

Amman, Jordan

King Abdullah University Hospital

🇯🇴

Irbid, Jordan

LSMUL Kauno klinikos

🇱🇹

Kaunas, Lithuania

Unidad Reumatologica Las Americas S.C.P

🇲🇽

Merida, Yucatan, Mexico

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Hanyang University Seoul Hospital

🇰🇷

Seoul, Korea, Republic of

Konkuk University Medical Center

🇰🇷

Seoul, Korea, Republic of

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

Southern Philippines Medical Center

🇵🇭

Davao, Davao DEL SUR, Philippines

St. Luke's Medical Center

🇵🇭

Quezon, Philippines

Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy

🇵🇱

Bydgoszcz, Poland

NZOZ Lecznica MAK-MED. S.C.

🇵🇱

Nadarzyn, Poland

Makati Medical Center

🇵🇭

Makati, Metro Manila, Philippines

Szpital Specjalistyczny im. J. Dietla Malopolskie Centrum Reumatologii Immunologii i Rehabilitacji

🇵🇱

Krakow, Poland

Spitalul Clinic de Recuperare Iasi

🇷🇴

Iasi, Romania

Clinical Hospital Center Bezanijska Kosa

🇷🇸

Belgrade, Serbia

Military Medical Academy

🇷🇸

Belgrade, Serbia

Komunalna ustanova "Zaporizka oblasna klinichna likarnia" Zaporizkoi oblasnoi rady

🇺🇦

Zaporizhzhia, Ukraine

Mohamed Kassab Institute of orthopedics

🇹🇳

Manouba, Tunisia

Kyivska miska klinichna likarnia #6

🇺🇦

Kyiv, Ukraine

Bahatoprofilnyi medychnyi tsentr (Universytetska klinika #1)

🇺🇦

Odesa, Ukraine

Wrightington Hospital

🇬🇧

Wigan, Lancashire, United Kingdom

Maidstone Hospital, Maidstone and Tunbridge wells NHS Trust

🇬🇧

Maidstone, United Kingdom

Accurate Clinical Research

🇺🇸

Nassau Bay, Texas, United States

The Seattle Arthritis Clinic

🇺🇸

Seattle, Washington, United States

Western Michigan University Homer Stryker MD School of Medicine Center for Clinical Research

🇺🇸

Battle Creek, Michigan, United States

Methodist Medical Center of IL

🇺🇸

Peoria, Illinois, United States

Jakaranda Hospital

🇿🇦

Pretoria, Gauteng, South Africa

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