This is an 8 week study to assess the efficacy and safety profile of PF-06651600 in seropositive subjects with rheumatoid arthritis with an inadequate response to methotrexate (up to approximately 50% of subjects may also have had an inadequate response to 1 anti-TNF biologic).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
70
200mg pill every day (QD) for 8 weeks
Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 8
The SDAI is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment (PtGA) and physician global assessment (PGA) assessed on a visual analogue scale (VAS) scale ranging from 0 to 10 centimeter (cm), where higher scores=greater affection due to disease activity, and C-reactive protein (CRP) measured in terms of milligram per deciliter (mg/dL). SDAI total score= 0 to 86. SDAI greater than or equal to (\<=) 3.3 indicates disease remission, greater than (\>) 3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.
Time frame: Baseline, Week 8
Number of Participants With Vital Signs Abnormalities
Criteria: sitting pulse rate less than (\<) 40 beats per minute (bpm) or \>120 bpm; sitting systolic blood pressure (SBP) \>=30 millimeters of mercury (mmHg) change from baseline in same posture or \<90 mmHg; diastolic blood pressure (DBP) \>=20 mmHg change from baseline in same posture or \<50 mmHg. Only those categories in which at least one participant had abnormality, were reported in this outcome measure.
Time frame: Baseline up to Week 12
Number of Participants With Laboratory Abnormalities
Hemoglobin(Hb);hematocrit;RBC count:\<0.8\*lower limit of normal (LLN),mean corpuscular volume;mean corpuscular Hb concentration:\<0.9\*LLN or\>1.1\*upper limit of normal (ULN), platelet:\<0.5\*LLN or \>1.75\*ULN,reticulocytes \<0.5\*LLN or \>1.5\*ULN,leukocytes \<0.6\*LLN or \>1.5\*ULN,lymphocyte;neutrophil: \<0.8\*LLN or \>1.2\*ULN,basophil;eosinophil; monocyte:\>1.2\*ULN,partial thromboplastin time,prothrombin time\>1.1\*ULN,bilirubin\>1.5\*ULN, aspartate aminotransferase; alanine aminotransferase;alkaline phosphatase:\>3.0\*ULN,protein;albumin;LDL, HDL cholesterol:\<0.8\*LLN or \>1.2\*ULN;urea nitrogen;creatinine: \>1.3\*ULN, urate \>1.2\*ULN, sodium\<0.95\*LLN or \>1.05\*ULN, potassium; chloride;calcium; bicarbonate:\<0.9\*LLN or \>1.1\*ULN,glucose \<0.6\*LLN or \>1.5\*ULN, creatine kinase: \>2.0\*ULN;urine pH \<4.5 or \>8,urine glucose or ketones\>=1,urine protein;urineHb\>=1,urobilinogen;bilirubin;nitrite;leukocyte esterase \>=1,urine erythrocytes, leukocytes\>=20,hyaline cast\>1,bacteria\>20.
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California Medical Research Associates Inc.
Northridge, California, United States
Clayton Medical Associates, PC
St Louis, Missouri, United States
Altoona Center For Clinical Research
Duncansville, Pennsylvania, United States
Southwest Rheumatology Research, LLC
Mesquite, Texas, United States
MHAT "Trimontsium" Department of Internal Diseases
Plovdiv, Bulgaria
UMHAT Kaspela, Clinic of Rheumatology
Plovdiv, Bulgaria
Medical Centre "Pirogov"
Sofia, Bulgaria
Medical Center Equita
Varna, Bulgaria
Medical Center "Sveti Ivan Rilski"
Vidin, Bulgaria
MEDICAL PLUS, s.r.o.
Uherské Hradiště, Czechia
...and 20 more locations
Time frame: Baseline up to Week 12
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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 are events between first dose of study drug and up to Week 12 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to Week 12
Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 1, 2, 4 and 6
The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on a VAS scale ranging from 0 to 10 cm, where higher scores=greater affection due to disease activity, and CRP measured in terms of mg/dL. SDAI total score= 0 to 86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.
Time frame: Baseline, Week 1, 2, 4 and 6
Remission Rate Based on Simple Disease Activity Index Score
Remission rate was defined as percentage of participants with disease remission. The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on a VAS scale ranging from 0 to 10 cm, where higher scores=greater affection due to disease activity, and CRP measured in terms of mg/dL. SDAI total score= 0 to 86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.
Time frame: Week 4, 6 and 8
Remission Rate Based on Disease Activity Score (DAS28-3 [ESR])
Remission rate was defined as the percentage of participants with disease remission. DAS28 is measure of disease activity in participants with rheumatoid arthritis. DAS28-3 (ESR) was calculated from SJC and TJC using 28 joints count, and erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (ESR) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (ESR) \<2.6 = remission.
Time frame: Week 4, 6 and 8
Remission Rate Based on Disease Activity Score (DAS28-4[ESR])
Remission rate was defined as the percentage of participants with disease remission. DAS28 is measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from the number of SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission.
Time frame: Week 4, 6 and 8
Remission Rate Based on Disease Activity Score (DAS28-3 [CRP])
Remission rate was defined as the percentage of participants with disease remission. DAS28 is measure of disease activity in participants with rheumatoid arthritis. DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.
Time frame: Week 4, 6 and 8
Remission Rate Based on Disease Activity Score (DAS28-4 [CRP])
Remission rate was defined as the percentage of participants with disease remission. DAS28 is measure of disease activity in participants with rheumatoid arthritis. 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.
Time frame: Week 4, 6 and 8
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) at Week 1, 2, 4, 6 and 8
DAS28 is measure of disease activity in participants with rheumatoid arthritis. DAS28-3 (ESR) was calculated from SJC and TJC using 28 joints count, and ESR (mm/hr). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (ESR) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (ESR) \<2.6 = remission.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 1, 2, 4, 6 and 8
DAS28 is measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 1, 2, 4, 6 and 8
DAS28 is measure of disease activity in participants. DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) \<= 3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) \<2.6 = remission.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 1, 2, 4, 6 and 8
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.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Concentration at Week 1, 2, 4, 6 and 8
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in the Tender Joint Count and Swollen Joint Count at Week 1, 2, 4, 6 and 8
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.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in Participant's Assessment of Arthritis Pain (PAAP), Participant's Global Assessment of Arthritis (PGA) and Physician's Global Assessment of Arthritis (PGAA) at Week 1, 2, 4, 6 and 8
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.
Time frame: Baseline, Week 1, 2, 4, 6 and 8
Change From Baseline in Health Assessment Questionnaire-Disability Index [HAQ-DI] at Week 1, 2, 4, 6 and 8
HAQ-DI assess degree of difficulty a participant experienced (during 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: average of the 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.
Time frame: Baseline, Week 1, 2, 4, 6 and 8