Rheumatoid Arthritis MedDRA version: 14.0 Level: LLT Classification code 10066578 Term: Progression of rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Code: PF-04171327
Pharmaceutical Form: Tablet
CAS Number: 1044535-58-1
Current Sponsor code: PF-04171327
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Sponsors
Pfizer, S.L.U.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 3. Males and females >18 years of age. 4. Subject should have RA (ACR criteria, 1987 revised criteria) with a minimum duration of 3 months and fulfilled 4/7 criteria for the diagnosis of RA. 5. Subject must have minimum disease activity level of at least: ?6 swollen joints and ?6 tender joints at screening and baseline (28 joint count); CRP ?0.7 mg/dL (?7.0 mg/L) at screening. 6. Meet the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II or III. 7. Subject must have been on MTX or allowed MTX-DMARD combination (eg, MTX + hydroxychloroquine or MTX + chloroquine or MTX + sulfasalazine) for at least 3 months, and be on a stable dose of MTX for at least 8 weeks prior to screening. MTX or allowed DMARD combination, as well as any concomitant medication(s) dose, will remain unchanged during the treatment period. 8. Subject must be on a stable MTX of dose ?7.5 mg weekly (po/sc/im) and ?25 mg weekly unless documented intolerance requires a lower dose. Stable MTX doses should be administered as a weekly single dose for a minimum of 8 weeks prior to randomization. 9. For subjects on chronic topical or inhaled glucocorticoids, the treatment must be stable for ?4 weeks prior to entry and remain unchanged throughout the study period. 10. No evidence of active or latent infection with Mycobacterium tuberculosis (TB) as defined by all of the following: A negative QuantiFERON; TB Gold In Tube test or, if unavailable, a Mantoux Purified Protein Derivative (PPD) skin test using 5 tuberculin units per 0.1 mL (5 TU PPD) result of =65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Diagnosis of any other arthritidies (inflammatory or non-inflammatory) or chronic pain condition (fibromyalgia, neuropathy) that, in the opinion of the investigator would interfere with disease activity assessments. 2. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological disease, or any other conditions which would make the subject unsuitable for the study. 3. Any lymphoproliferative disorder, such as Epstein-Barr Virus (EBV), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma or signs andsymptoms suggestive of current lymphatic disease. 4. A prior history of malignancy, excluding subjects with non-metastic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, who are eligible immediately after adequate treatment. 5. Blood dyscrasis including confirmed:Hemoglobin 1.2 ULN. 9. Subject diagnosed with insulin dependent diabetes mellitus or poorly controlled noninsulin dependent diabetes mellitus (HgbA1c value of >8.0%). 10. Drug or alcohol abuse with less than 6 months of continued abstinence prior to the screening visit. 11. Clinically significant infections (those requiring hospitalization or requiring parenteral antimicrobial therapy) within 6 months of the screening visit. 12. A body temperature of 38?C or higher at the baseline visit or a febrile illness within 14 days prior to the first dose. 13. An infection with human immunodeficiency virus (HIV) or Hepatitis B or C. 14. Any condition possibly affecting oral drug absorption 15. Significant trauma, blood loss or major surgery (involving anesthesia or respiratory assistance within 4 weeks of the screening visit). 16. Bone fracture and/or immobility/immobilization within 3 months of the screening visit. 17. A standard 12-lead ECG demonstrating a QTcF >450 ms for males and QTcF >480 ms for females or other clinically significant abnormality at the screening visit If t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To compare efficacy and safety of PF-04171327 (1, 5, 10 mg, 15 mg once daily) to 5 mg daily prednisone, 10 mg daily prednisone and placebo given over 8 weeks, in subjects with active RA on a stable background of MTX; - Determine comparative therapeutic window of PF-04171327 using ACR 20 responses and change from baseline in P1NP and UNTx/Ucr, (primary set of biomarkers) ie, determining a dose, or a range of doses, in which there is sufficient efficacy on the ACR20 and minor changes in P1NP and UNTx/Ucr.;Secondary Objective: To characterize the dose-effect and concentration-effects for efficacy, safety and biomarker outcome measures; - To characterize the effects of PF-04171327 on the bone and carbohydrate biomarkers compared to prednisone 5 mg, 10 mg, and placebo; -To examine the durability of the response to PF-04171327; -To evaluate the tapering of PF-04171327; -To evaluate the safety and tolerability of PF-04171327; - To evaluate health and functional status of study subjects.;Primary end point(s): - Efficacy: ACR20 at week 8; Primary set of dissociation biomarkers: P1NP, and UNTx/Ucr at week 8.;Timepoint(s) of evaluation of this end point: Study Week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: - ACR20 at 2, 4 and 12 weeks; ACR50, ACR70, Hybrid ACR response, Individual ACR components, all at week 2, 4, 6, 8 and 12; - DAS 28-3 (CRP), DAS28-4 (CRP) at week 2, 4, 6, 8 and 12; - SF-36 v 2 (Quality of Life) at week 4, 8, and 12. Pharmacokinetic and Pharmacodynamic endpoints: - Plasma concentrations of PF-00251802 and its N-Oxide metabolite PF-04015475 (baseline, week 2, 4, 6 and 8 - Pharmacodynamic effects will be assessed by several biomarkers, such as serum CTX, osteocalcin, PTH and adiponectin at baseline, week 2, 4, 6, 8, 10, 12 and 13. Safety endpoints: -Biomarkers: plasma cortisol, CRP, will be obtained at baseline, week 2, 4, 6, 8, 10, 12 and 13 - Circulating lymphocytes, neutrophils, and eosinophil counts will be obtained at 4,8 and 12 weeks - HbA1C(baseline week 8 and 12), and fasting glucose at week 0,4,8 and 12. Safety outcomes: Assessment of taper period, HPA axis labs (ACTH stimulation test (week 13 after one week of study drug discontinuation), vital signs, telephone follow up (taper period), AE reports, routine labs (including liver tests), concomitant meds (esp. diabetes meds, glucocorticoids other than study drug).;Timepoint(s) of evaluation of this end point: Study Weeks 2, 4, 6, 8 and 12 | — |
Countries
Bulgaria, Canada, Colombia, Czech Republic, Germany, Hungary, India, Korea, Republic of, Malaysia, Mexico, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Ukraine, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed