A Study Of PF-04171327 In The Treatment Of The Signs And Symptoms Of Rheumatoid Arthritis

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, ACTIVE AND PLACEBO-CONTROLLED STUDY OF PF-04171327 IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF RHEUMATOID ARTHRITIS

This study will investigate the safety and efficacy of an investigational drug, PF-04171327 on the signs and symptoms of rheumatoid arthritis in patients that require glucocorticoids while on background methotrexate. This study will also look at the response of chemical and biological markers in rheumatoid arthritis patients. Lastly, this study will measure the PK (amount of drug in the blood) of methotrexate while patients may be taking PF-04171327.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: PF-04171327 10 mg; Other: Prednisone Placebo; Drug: PF-04171327 25 mg; Drug: Prednisone 5 mg; Other: Placebo for PF-04171327; Other: Placebo for PF-04171327; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Ceske Budejovice, Czechia, 370 01
    • MEDIPONT Plus, s.r.o.
  • Hostivice, Czechia, 253 01
    • ARTMEDI UPD s r.o.
  • Praha 11 - Chodov, Czechia, 148 00
    • DC Mediscan
  • Praha 4, Czechia, 140 00
    • Revmatologicka ambulance
  • Praha 4, Czechia, 140 59
    • Fakultni Thomayerova nemocnice s poliklinikou
• Hong Kong
  • New Territories, Hong Kong
    • Centre for Assessment and Treatment of Rheumatic Diseases, Department of Medicine and Geriatrics
• Hungary
  • Bekescsaba, Hungary, 5600
    • Dr. Rethy Pal Korhaz es Rendelointezet\Reumatologia
  • Budapest, Hungary, H-1036
    • Synexus Magyarorszag Kft.
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum
  • Szolnok, Hungary, H-5000
    • MAV Korhaz es Rendelointezet
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University College of Medicine, Rheumatology, Internal Medicine
• Russian Federation
  • Moscow, Russian Federation, 115093
    • Moscow SHI City Clinical Hospital #4, Department of Therapy of Moscow Faculty
  • Moscow, Russian Federation, 115522
    • Institution of Russian Academy of Medical Sciences Research Institute of Rheumatology RAMS
  • Saint-Petersburg, Russian Federation, 192242
    • SI Saint-Petersburg SRI for Emergency Care named after I.I. Dzhanelidze
  • Smolensk, Russian Federation, 214018
    • Regional State Institution of Healthcare Smolensk Regional Clinical Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology
  • Niska Banja, Serbia, 18205
    • Institute for Rheumatic and Cardiovascular Disease Niska Banja
• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital
• Slovakia
  • Piestany, Slovakia, 921 12
    • Narodny ustav reumatickych chorob, Klinicke oddelenie
  • Zilina, Slovakia, 010 01
    • Nestatna reumatologicka ambulancia, MUDr. Pavol Polak, s.r.o.
• Spain
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Hospital Nuestra Señora de La Esperanza
  • Bilbao
    • Baracaldo, Bilbao, Spain, 48903
      • Hospital de Cruces
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University School fo Medicine
• Ukraine
  • Kharkiv, Ukraine, 61176
    • Chair of Cardiology & Functional Diagnostic
  • Kyiv, Ukraine, 04114
    • State Institution "Institute of Gerontology of AMS of Ukraine"
  • Kyiv, Ukraine, 04114
    • State Institution 'Institute of Gerontology of AMS of Ukraine'
  • Lviv, Ukraine, 79011
    • Municipal City Clinical Hospital #4, Department of Rheumatology
  • Vinnitsa, Ukraine, 21018
    • Vinnitsa Regional Clinical Hospital n.a. Pirogov
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Anniston, Alabama, United States, 36207
      • Anniston Medical Clinic, PC
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Allergy, Asthma, Arthritis and Lung
    • Miami, Florida, United States, 33169
      • Elite Research Institute
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic, PA
  • Illinois
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Quest Research Institute
    • Bingham Farms, Michigan, United States, 48025
      • Premier Imaging Center
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years of age, diagnosed with rheumatoid arthritis for a minimum duration of 3 months
• On stable dose of methotrexate for at least 6 weeks prior to screening
• Patient must have minimum disease activity level of ≥ 6 tender/painful joints, ≥ 6 swollen joints and CRP ≥ 0.7 mg/dL
• Not currently receiving steroid medication

Exclusion Criteria:

• Pregnant or nursing women
• Patients that have active infections, TB, HIV and/or Hepatitis B or C
• Patients that have a history of intolerance or significant adverse effects with the use of glucocorticoids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo for PF-04171327; Placebo for PF-04171327 every day for 14 days; Other: Placebo for PF-04171327; Placebo tablet every day for 14 days; Other: Placebo; Placebo tablet every day for 14 days
Active Comparator: Prednisone	Drug: Prednisone 5 mg; Prednisone 5 mg tablet every day for 14 days; Other: Placebo for PF-04171327; Placebo for PF-04171327 every day for 14 days; Other: Placebo for PF-04171327; Placebo tablet every day for 14 days
Experimental: PF-04171327 10 mg	Drug: PF-04171327 10 mg; PF-04171327 10 mg tablet every day for 14 days; Other: Prednisone Placebo; Placebo for Prednisone 5 mg tablet every day for 14 days
Experimental: PF-04171327 25 mg	Other: Prednisone Placebo; Placebo for Prednisone 5 mg tablet every day for 14 days; Drug: PF-04171327 25 mg; PF-04171327 25 mg tablet every day for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Day 14	DAS28-4 (CRP) examines progression or improvement of RA. It was assessed from swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, CRP (normal range of CRP is less than (<) 10 milligram per liter [mg/L], decrease in the level of CRP indicates reduction in inflammation) and participant global assessment (PGA) of disease activity (participant global assessment of diseases condition scores ranging from 0 [very well condition] to 100 [very poor condition], higher scores indicated greater affectation due to disease activity). Total DAS28-4 (CRP) transformed score range: 0 (least severe) to 10 (most severe), higher scores indicate more severe disease activity. DAS28-4 (CRP) scores: less than equal to (<=) 3.2 implied low disease activity; greater than (>) 3.2 to 5.1 implied moderate to high disease activity.	Baseline, Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tender Joints Count at Day 7, 14, 42	Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.	Baseline, Day 7, 14, 42
Change From Baseline in Swollen Joints Count at Day 7, 14 and 42	Number of swollen joints was determined by examination of 28 joints and identifying if swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.	Baseline, Day 7, 14, 42
Change From Baseline in C-Reactive Protein (CRP) at Day 7, 14 and 42	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is less than (<) 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.	Baseline, Day 7, 14, 42
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Day 7 and 14	HAQ-DI assessed the ability of participants to perform task in 8 domains of daily living activities: dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities. Each item was scored on a 4-point scale ranging from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do, higher scores indicate more difficulty. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible HAQ-DI score range: 0 (no difficulty) to 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.	Baseline, Day 7, 14
Change From Baseline in Participant Assessment of Arthritis Pain at Day 7 and 14	Participant assessment of arthritis pain included assessment of severity of arthritis pain using a 100 millimeter (mm) visual analog scale (VAS). Participants placed a mark on the VAS between 0 mm (no pain) and 100 mm (most severe pain), which corresponded to the magnitude of their pain, higher scores indicate more pain.	Baseline, Day 7, 14
Change From Baseline in Participant Global Assessment (PGA) of Arthritis at Day 7 and 14	PGA was a questionnaire where participants answered the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The participants' response were recorded using a 100 mm visual analog scale placing a mark on the scale, between 0 mm (very well condition) to 100 mm (very poor condition). Higher scores indicate higher degree of arthritis.	Baseline, Day 7, 14
Change From Baseline in Physician Global Assessment (PhGA) of Arthritis at Day 7 and 14	PhGA included assessment of severity of arthritis pain where physicians were asked to rate the severity of the participant's overall arthritis. The physician's response was recorded using a visual analog scale between 0 mm (very good condition) to 100 mm (very poor condition). Higher scores indicate higher degree of arthritis.	Baseline, Day 7, 14
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) at Day 14	SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Score for each of the 8 aspects are scaled from 0 (worst condition) to 100 (best condition), where higher scores indicate better health status. These 8 domains were also reported as two summary scores: physical component scores and mental component scores. Score range for each of the 2 summary scores = 0 (worst condition) to 100 (best condition), where higher scores represent better health status.	Baseline, Day 14 (D14)
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 7, 14 and 42	DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (normal range of CRP is <10 mg/L, decrease in the level of CRP indicates reduction in inflammation). Total DAS28-3 (CRP) score range: 0 (least severe) to 9.4 (most severe), higher scores indicate more disease activity.	Baseline, Day 7, 14, 42
Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Day 7	DAS28-4 (CRP) examines progression or improvement of RA. It was assessed from SJC and TJC using the 28 joints count, CRP (normal range of CRP is <10 mg/L, decrease in the level of CRP indicates reduction in inflammation) and PGA of disease activity (participant global assessment of diseases condition scores ranging from 0 [very well condition] to 100 [very poor condition], higher scores indicated greater affectation due to disease activity). Total DAS28-4 (CRP) transformed score range: 0 (least severe) to 10 (most severe), higher scores indicate more severe disease activity. DAS28-4 (CRP) scores: <=3.2 implied low disease activity; >3.2 to 5.1 implied moderate to high disease activity.	Baseline, Day 7
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Day 7 and 14	ACR20 responder: participants who achieved at =20% improvement in tender and swollen 28-joints count, and >=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0[no pain] to 100[most severe pain], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0[no difficulty] to 3[extreme difficulty], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is <10 mg/L, decrease in the level of CRP=reduction in inflammation).	Day 7, 14
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 7 and 14	ACR50 responder: participants who achieved at =50% improvement in tender and swollen 28-joints count, and >=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0[no pain] to 100[most severe pain], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0[no difficulty] to 3[extreme difficulty], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is <10 mg/L, decrease in the level of CRP=reduction in inflammation).	Day 7, 14
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Day 7 and 14	ACR70 responder: participants who achieved at =70% improvement in tender and swollen 28-joints count, and >=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of arthritis pain (participant's self-assessed severity of arthritis pain, score range from 0[no pain] to 100[most severe pain], higher scores=more pain), 2) PGA of arthritis (participant's assessed overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 3) PhGA of arthritis (physician rated severity of participants overall arthritis activity, score range from 0[no arthritis] to 100[extreme arthritis], higher scores=higher degree of arthritis), 4) HAQ-DI (assessment of functional disability, score range from 0[no difficulty] to 3[extreme difficulty], higher scores=more functional limitation) and 5) CRP (assessment of inflammation, normal range of CRP is <10 mg/L, decrease in the level of CRP=reduction in inflammation).	Day 7, 14
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. An 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 31 days after last dose (Day 45) that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to Day 45
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities	Criteria for laboratory abnormalities: Hematology (hemoglobin, hematocrit <0.8*baseline; platelet count <75 or >700*10^3 per mm^3; leucocytes <2.5 or >17.5*10^3 per mm^3); chemistry (total bilirubin >1.5*upper limit of reference range [ULN]; aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, >3.0*ULN; total protein, albumin <0.8*lower limit of reference range [LLN] or >1.2*ULN; blood urea nitrogen [BUN]/urea, creatinine >1.3*ULN; glucose [fasting] <0.6*LLN or >1.5*ULN; uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN; potassium, calcium <0.9*LLN or >1.1*ULN; albumin, total protein <0.8*LLN or >1.2*ULN; urinalysis (urine white blood cell (WBC) =>6/ high power field (hpf); urine red blood cell (RBC) =>6/hpf). Number of participants with clinically significant change from baseline in laboratory abnormalities identified by investigator were reported.	Baseline up to Day 45
Change From Baseline in Body Weight at Day 7 and 14		Baseline, Day 7, 14
Number of Participants With Clinically Significant Vital Signs Abnormalities	Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate and body temperature. Vital sign measurements were performed with the participant in the seated position. Clinical significance vital sign abnormality was determined by investigator.	Baseline up to Day 45
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Clinically significant ECG findings included PR interval >=300 milliseconds (msec) or >=25% increase from baseline (if baseline PR interval >200 msec) or >=50% increase (if baseline PR interval less than or equal to [<=] 200 msec); QRS interval >=200 msec or >=25% increase from baseline (if baseline PR interval >100 msec) or >=50% increase (if baseline PR interval <= 100 msec); QT interval >=500 msec, corrected QT interval >=500 msec.	Baseline up to Day 45
Plasma Concentration of PF-00251802 Versus Time Summary on Day 7 and Day 14	Plasma concentration of PF-00251802 versus time summary, a metabolite of PF-04171327 was reported in this outcome measure.	0, 1, 2, 3 and 4 hours post-dose on Day 7, 14
Ratio of Apparent Oral Clearance on Day 1 to Day 14 of Methotrexate	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Methotrexate was used as a background therapy by participants.	Pre-dose (0 hour), 1, 2, 3 and 4 hours post-dose
Change From Baseline in Lymphocyte Counts at Day 1, 7 and 14		Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14
Change From Baseline in Neutrophil Counts at Day 1, 7 and 14		Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14
Change From Baseline in Eosinophil Counts at Day 1, 7 and 14		Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14
Change From Baseline in Osteocalcin Level at Day 1, 7 and 14		Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14
Change From Baseline in Plasma Cortisol Level at Day 1, 7 and 14		Baseline; 1, 2, 3 and 4 hours post-dose on Day 1; 0, 1, 2, 3 and 4 hours post-dose on Day 7 and 14
Change From Baseline in Ratio of Urinary N-terminal Telopeptide of Type 1 Collagen (uNTX-I) Level to Urinary Creatinine (uCr) Level at Day 7 and 14	Unit of ratio of urinary N-terminal telopeptide of type 1 collagen (uNTX-I) level to urinary creatinine (uCr) level was nanomoles bone collagen equivalents (nmol bce) per millimole creatinine (mmol cr).	Baseline, Day 7 and 14
Change From Baseline in Adiponectin Level at Day 7 and 14		Baseline, Day 7 and 14

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2009
• Primary Completion (Actual): July 29, 2010
• Study Completion (Actual): July 29, 2010

Study Registration Dates

• First Submitted: July 13, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimated): July 14, 2009

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis Glucocorticoids Prednisone
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: A9391005; 2009-013223-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.