Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: PF-06650833
Drug: Placebo
Drug: Tofacitinib

Registration Number: NCT02996500

Lead Sponsor: Pfizer

Brief Summary: This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered orally BID for 12 weeks in a blinded fashion.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 269

Inclusion Criteria

Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.
Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
The subject has active disease at both Screening and Baseline, as defined by both:
- 6 joints tender or painful on motion, AND
- 6 joints swollen; and fulfills 1 of the following 2 criteria at Screening:
- High sensitivity C reactive protein (hsCRP) >7 mg/L at screening
- Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;
Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
Subjects must be ACPA positive between screening and randomization.
Subjects must have been taking oral MTX for at least 3 months at an adequate dose to determine that the subject had an inadequate response to MTX
Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered that was inadequately effective and/or not tolerated. The anti-TNF biologic could also have been discontinued due to lack of continued access.

Exclusion Criteria

Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
Subjects with any of the following infections or infections history:
1. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
2. Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
3. Infected joint prosthesis at any time with the prosthesis still in situ.
4. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
5. Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.
6. Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
7. Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
8. Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.
Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
Pre-existing chronic autoimmune disease.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3: 200 mg QD	PF-06650833	Pf-06650833, 200 mg QD
Arm 1: 20 mg QD	PF-06650833	PF-06650833 , 20 mg QD
Arm 2: 60 mg QD	PF-06650833	PF-06650833, 60 mg QD
Placebo	Placebo	Placebo, 0 mg BID
Arm 4: 400 mg QD	PF-06650833	PF-06650833, 400 mg QD
Arm 5: Tofacitinib	Tofacitinib	Tofacitinib 5 mg BID

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12	Baseline and Week 12	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = Tender / Painful Joint Count(TJC) (using 28 joints) + Swollen Joint Count (SJC) (using 28 joints) + Patient Global Assessment of Arthritis (PtGA) (0-10 cm scale) + Physician's Global Assessment of Arthritis (PhGA) (0-10 cm scale) + high sensitivity C-reactive protein (hsCRP) (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity. The primary analysis utilized a Bayesian ANCOVA model with an informative placebo prior distribution with borrowing from tofacitinib historical placebo data. The confidence interval was credible interval in this statistical analysis. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in SDAI at Weeks 4 and 8	Baseline, Weeks 4 and 8	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity. The descriptive summary of change from baseline in SDAI was based on a mixed effect model repeat measurement MMRM model with observed data. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI LDAS was SDAI\<=11. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = TJC (using 28 joints) + SJC (using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale) + hsCRP (mg/dL). The criterion of SDAI remission was SDAI\<=3.3. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (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)\*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28\<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	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, hs-CRP and PtGA. 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 (PtGA \[mm\]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28\<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR \[mm/first hour\] + 0.014 (PtGA \[mm\]). Higher score indicated more disease activity. Total score range: 0-9.4. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR) \[mm/first hour\]\*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	ACR20 was calculated as a 20% improvement in TJC and SJC and 20% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	ACR50 was calculated as a 50% improvement in TJC and SJC and 50% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	ACR70 was calculated as a 70% improvement in TJC and SJC and 70% improvement in 3 of the 5 remaining ACR core set measures: PtGA and PhGA, pain, disability, and an acute phase reactant which for this study was CRP or ESR. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	The TJC (28) included the following joints: shoulders, elbows, wrists, metatarsophalangeal (MCP) joints, PIP joints, and knees. This count was calculated from the TJC (68) assessed. The SJC (28) included the same joints as TJC (28), and was calculated from the SJC 66 assessed for swelling.Sixty eight (68) joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. The 68 joints assessed were: temporomandibular, sternoclavicular, acromioclavicular; shoulder, elbow, wrist, MCPs, thumb interphalangeal, proximal interphalangeals, and distal interphalangeals; hip, knee, ankle, tarsus, metatarsophalangeals, great toe interphalangeal, proximal and distal interphalangeals combined. Sixty-six (66) joints were assessed for swelling, the same as those listed for TJC, excluding the right and left hip joints. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR \[mm/first hour\] + 0.014 (PtGA \[mm\]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 (ESR) LDAS was DAS28\<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR \[mm/first hour\]\*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28\<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and ESR. DAS28-3 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR \[mm/first hour\]\*1.08+0.16. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 LDAS was DAS28\<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks	Weeks 4, 8 and 12	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, hs-CRP and PtGA. 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 (PtGA \[mm\]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 LDAS was DAS28\<3.2. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (ESR) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, ESR and PtGA. DAS28-4 (ESR) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.70 ln(ESR \[mm/first hour\] + 0.014 (PtGA \[mm\]). Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-4 remission was DAS28\<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks	Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (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)\*1.10+1.15. Total score range: 0-9.4. Higher score indicated more disease activity. The criterion of DAS28-3 remission was DAS28\<2.6. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	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, hs-CRP and PtGA. 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 (PtGA \[mm\]) + 0.96. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-3 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed and hs-CRP. DAS28-3 (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)\*1.10+ 1.15. Total score range: 0-9.4. Higher score indicated more disease activity. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks	Baseline, Weeks 4, 8 and 12	Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks	Baseline, Weeks 4, 8 and 12	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 was independent of the participant's reported assessments of PtGA (patient's global assessment of arthritis). 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". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.
Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)	Vital Signs tests included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and pulse rate. Vital signs categorical summarization criteria were 1), systolic BP (SBP) \<90 millimeters of mercury (mm Hg) or change from baseline (Chg) \>=30mm Hg; diastolic BP (DBP) \<50mm Hg or change from baseline \>=20mm Hg; 2), pulse rate \<40bpm or \> 120bpm.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)	ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and QTc calculated using Bazett's correction factor (QTcB interval).
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12	Baseline, Weeks 4, 8 and 12	The HAQ-DI was defined as participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)	Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Each parameter was evaluated against commonly used and widely accepted criteria. Clinical significance of laboratory parameters was determined at the investigator's discretion. The investigator judged the abnormality.
Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12	Baseline, Weeks 4, 8 and 12	Patients answer the following question: "Considering all the ways your arthritis affects you, how are you feeling today?" The patient's response is recorded using a 100 mm VAS. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. The higher score indicated more severe disease. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Number of Participants With Urinalysis Data Meeting Pre-specified Criteria	Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months)	The urine sample was collected for central laboratory urinalysis and urine microscopy. The urinalysis included pH, protein, glucose, erythrocytes, leukocytes, ketones, nitrite, urobilinogen, urine bilirubin, urine hemoglobin, leukocyte esterase, granular casts, hyaline casts, bacteria, atypical, needle-like crystals urine, specific gravity, microscopy and urine albumin test.
Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12	Baseline, Weeks 4, 8 and 12	Patients assess the severity of their arthritis pain using a 100 mm VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain. This assessment was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12	Baseline and Week 12	The SF-36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The SF-36 summary scores range from 0-100, with higher scores representing better self-reported health. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12	Baseline and Week 12	The SF 36 version 2 (acute) is a 36 item generic health status measure. It measures 8 general health domains. These domains can also be summarized as physical component score (PCS) and mental component score (MCS). The PCS and MCS summary scores range from 0-100, with higher scores representing better self-reported health. The lower the score the more disability. This was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or Investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12	Baseline and Week 12	The EQ-5D-3L health state profile is a patient completed questionnaire designed to assess impact on health related quality of life in 5 domains: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Additionally, scores from the 5 domains might have been used to calculate a single index value, also known as a utility score. The validity and reliability of the EQ-5D-3L have been established in a number of disease states, including RA. EQ-5D-3L scores marked health status from 0 and 100. There were notes at the both ends of the scale that the bottom rate (0) corresponded to " the worst health you could imagine", and the highest rate (100) corresponded to "the best health you could imagine". Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12	Baseline and Week 12	The FACIT-F is a patient completed questionnaire consisting of 13 items that assess fatigue. Instrument scoring yields a range from 0 to 52, with higher scores representing better patient status (less fatigue). This questionnaire was performed early in the clinic visit and before the participant had extensive contact with site personnel and/or investigator. Tofacitinib was included in this study as an active control. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

Trial Locations

Locations (99): Clinical and Translational Research Center of Alabama, PC
🇺🇸
Tuscaloosa, Alabama, United States
Dory Hardy, PharmD
🇺🇸
Tucson, Arizona, United States
Southern Arizona VA Health care System
🇺🇸
Tucson, Arizona, United States
Robert W. Levin, MD,PA
🇺🇸
Clearwater, Florida, United States
Millennium Research
🇺🇸
Ormond Beach, Florida, United States
Arthritis & Rheumatic Care Center
🇺🇸
South Miami, Florida, United States
Qps-Mra, Llc
🇺🇸
South Miami, Florida, United States
Medical Associates of North Georgia
🇺🇸
Canton, Georgia, United States
Graves Gilbert Clinic
🇺🇸
Bowling Green, Kentucky, United States
Arthritis and Diabetes Clinic, Inc.
🇺🇸
Monroe, Louisiana, United States
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Clinical and Translational Research Center of Alabama, PC
🇺🇸Tuscaloosa, Alabama, United States