Phase 3 Randomized, Double-Blind Study of the Efficacy and Safety of 2 Doses of CP-690,550 Compared to Methotrexate in Methotrexate-Naïve Patients with Rheumatoid Arthritis

Phase 1

• Conditions: Moderate to severe active Rheumatoid Arthritis; MedDRA version: 15.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2009-016987-34-SK
• Lead Sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017, USA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-28
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Active, moderate to severe, rheumatoid arthritis with joint erosions or positive IgM Rheumatoid Factor (RF) or antibodies to cyclic citrullinated peptide (anti-CCP).
2. Meet all eligibility criteria outlined below.
Active Rheumatoid Arthritis
To be eligible for participation in this trial, a patient must meet the following criteria:
1. The patient must meet the American College of Rheumatology (ACR) classification criteria for the diagnosis of rheumatoid arthritis (RA) by satisfying at least four of the seven criteria.
2. Evidence of at least three distinct joint erosions on posteroanterior (PA) hand and wrist or anteroposterior (AP) foot radiographs (locally read) OR if radiographic evidence of joint erosion is not available, patient must have a positive IgM rheumatoid factor (RF+), as determined by an acceptable laboratory method, OR antibodies to cyclic citrullinated peptide (anti-CCP+), as determined by an acceptable laboratory method.
3. The patient must have active disease at both screening and baseline, as defined by having both:
a. =6 tender/painful joints on motion, and;
b. =6 swollen joints.
4. The patient must have one of the following criteria at screening:
• Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr, or;
• C-reactive protein (CRP) >7 mg/L in the central laboratory
5. The patient must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
Other Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before patients are included in the study.
• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
• Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
A patient with a diagnosis of rheumatoid arthritis must also meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Patient must be at least 18 years of age or older;
2. Patient has discontinued all disallowed concomitant medications for the required time prior to the first dose of study drug and is taking only those concomitant medications in doses and frequency allowed by the protocol;
3. Women of childbearing potential must test negative for pregnancy prior to enrollment in this study;
4. Sexually active women of childbearing potential and men whose partners are women of childbearing potential are required to use two adequate contraceptive methods during participation in this trial, as required for men and women on methotrexate therapy.
5. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by all of the following:
• A negative QuantiFERON®-TB Gold In-Tube test or, if unavailable or indeterminate
upon retest, a Mantoux Purified Protein Derivative skin test result of <5 mm of induration, performed according to local standards within the 3 months prior to screening. [Patients with a history of Bacille Calmette Guérin (BCG) vaccination will be tested with the QuantiFERON®-TB Gold In-Tube test];
• A chest radiograph taken at the Screening visit or within the 3 months prior to screening wit

Exclusion Criteria

Patients presenting with any of the following will not be included in the study:
1. Patients who have received more than 3 weekly doses of MTX or, if 3 or less weekly doses were received, MTX was stopped due to adverse event attributed to methotrexate.
2. Pregnancy or currently lactating.
3. Blood dyscrasias, including confirmed:
a. Hemoglobin <9 g/dL or Hematocrit <30%;
b. White blood cell count <3.0 x 10 to the power 9/L;
c. Absolute neutrophil count <1.2 x 10 to the power 9/L;
d. Platelet count <100 x 10 to the power 9/L
4. Estimated GFR <60 ml/min based on the formula for estimating GFR developed by the Modification of Diet in Renal Disease (MDRD)
5. AST or ALT greater than 1.5 times the upper limit of normal at screening or any uncontrolled clinically significant laboratory abnormality
6. Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic (including clinically significant hypercholesterolemia), endocrine, pulmonary, cardiac or neurologic disease, including pleural effusions or ascites; and conditions contraindicating treatment with MTX, including presence of severe or significant renal or significant hepatic impairment.
7. Severe, progressive or uncontrolled chronic liver disease including fibrosis, cirrhosis, or recent or active hepatitis.
8. History of any other rheumatic autoimmune disease, other than Sjogren’s syndrome.
9. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
10. History of any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
11. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
12. History of any infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug.
13. History of any infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug.
14. Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies Patients who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal CD 19/20+ counts by FACS analysis.
15. Any patient who has been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study drug or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks following discontinuation of study drug.
16. A patient with any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary.
17. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug.
18. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety.
19. A patient with a first degree relative with a hereditary immunodeficiency.
20. A patient with a malignancy or with a history of malignancy, with the exceptio

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified