PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF 2 DOSES OF CP-690,550 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS ON BACKGROUND DMARDS

• Register: EUCTR
• Last refreshed on: 19 November 2012
• Main ID: EUCTR2008-008337-11-SE
• Date of registration: 23/03/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF 2 DOSES OF CP-690,550 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS ON BACKGROUND DMARDS
• Scientific title: PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF 2 DOSES OF CP-690,550 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS ON BACKGROUND DMARDS
• Date of first enrolment: 27/05/2009
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008337-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, Finland, Germany, Greece, Poland, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1.Rheumatoid arthritis with evidence of disease activity by joint counts and laboratory markers of inflammation.
2.Ongoing treatment with a traditional background DMARD.
3.Meet all other eligibility criteria.

1.Rheumatoid Arthritis Disease Activity:
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 classification criteria for the diagnosis of rheumatoid arthritis.
2.The patient must have active disease at both screening and baseline, as defined by having both:
a.=4 tender/painful joints on motion (out of 68 joints assessed); and
b.=4 swollen joints (out of 66 joints assessed).
3.The patient must also have active disease as defined fulfilling 1 of the 2 following criteria at screening only:
a.Erythrocyte sedimentation rate >28 mm/hr; or
b.C reactive protein >7 mg/L.
4.The patient must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.

2.Background DMARD:
To be eligible for participation in this trial, a patient must meet the following criteria: 1.Patient must have had an inadequate response to at least one DMARD (traditional or biologic) due to lack of efficacy or toxicity.
2.Patient must remain on at least one background traditional DMARD and be dosed in accordance with the local regulatory label and be willing to remain on that traditional DMARD throughout the course of the study. Combination therapy will be allowed as consistent with local standards.
a.Methotrexate: Maximum dose of 25 mg/week. Minimum duration of therapy 4 months and dose stable for 6 weeks prior to first dose of study drug. Patients on methotrexate should be on an adequate and stable dose of folic acid (not less than 5 mg weekly, unless higher doses would violate the local label) for at least 4 weeks prior to the first dose of study drug.
b.Sulfasalazine: Maximum dose of 3 gm/day. Minimum duration of therapy 2 months and dose stable for 4 weeks prior to first dose of study drug.
c.Leflunomide: Maximum dose of 20 mg/day. Minimum duration of therapy 4 months and dose stable for 4 weeks prior to first dose of study drug.
d.Hydroxychloroquine sulfate: Maximum dose of 400 mg/day. Minimum duration of therapy 2 months and dose stable for 4 weeks prior to first dose of study drug.
e.Injectable Gold: Maximum dose of 50 mg/week. Minimum duration of therapy 6 months and dose stable for 3 months prior to first dose of study drug.
f.Penicillamine: Maximum dose of 1000 mg/day. Minimum duration of therapy 6 months and dose stable for 3 months prior to first dose of study drug.
g.Other traditional DMARDs may be considered after discussion with the Sponsor.

3.Other Inclusion Criteria:
Patients must meet all of the following inclusion criteria:
1.Evidence of a 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.
2.Patient must be at least 18 years of age or older.
3.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.
4.Women of childbearing potential must test negative for pregnancy prior to enrollment in this study.
5.Sexually active women of child
Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1. Any DMARD use that would be contraindicated according to the local prescribing information, including use as a background medication.
2. Pregnant or lactating females.
3. Blood dyscrasias including confirmed:
• Hemoglobin <9 g/dL or Hematocrit <30%;
• White blood cell count <3.0 x 10 to the power 9/L;
• Absolute neutrophil count <1.2 x 10 to the power 9/L;
• Platelet count <100 x 10 to the power 9/L.
4. Estimated GFR <40 ml/min based on Cockcroft-Gault calculation.
5. AST or ALT greater than 1.5 times the upper limit of normal at screening or any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the patient’s participation in the study.
6. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, metabolic, pulmonary, cardiac, or neurological disease.
7. History of any other rheumatic autoimmune disease other than Sjogren’s syndrome.
8. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
9. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
10. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
11. History of 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.
12. History of any infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug.
13. Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies [eg, alemtuzumab (Campath®), alkylating agents (eg, cyclophosphamide or chlorambucil), total lymphoid irradiation, etc]. 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.
14. 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.
15. 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.
16. History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug.
17. Screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect patient safety or interpretation of study results.
18. A patient with a first-degree relative with a hereditary immunodeficiency.
19. A patient with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell
cancer of the skin or cervical carcinoma in situ.
20. Significant trauma or major surgery within 1 mont

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Code: CP-690,550
Pharmaceutical Form: Film-coated tablet
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 1. To compare the efficacy of CP-690,550 in doses of 5 mg BID and 10 mg BID versus
placebo for the treatment of signs and symptoms of RA in patients with active RA
who have had an inadequate response to a DMARD (traditional or biologic), as
measured by ACR20 response rates at Month 6.
2. To compare physical function status of patients after administration of CP-690,550 in
doses of 5 mg BID or 10 mg BID versus placebo using the HAQ-DI at Month 3
compared to baseline in patients with active RA on background traditional DMARDs.
3. To compare the rate of achieving DAS 28-4(ESR) <2.6 at Month 6 in patients with
active RA after administration of CP-690,550, in doses of 5 mg BID and 10 mg BID
versus placebo.
4. To evaluate the safety and tolerability of CP-690,550 in doses of 5 mg BID and
10 mg BID versus placebo in patients with active RA on background traditional
DMARDs.

Secondary Objective: 1. To compare the efficacy of CP-690,550 in doses of 5 mg BID and 10 mg BID versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) in patients with active RA on background traditional DMARDs, as measured by ACR20 response rates at Months 1 and 3 and ACR50, ACR70 and DAS 28 response rates at Months 1, 3, and 6.
2. To compare the durability of ACR20, ACR50, and ACR70 and DAS 28 response rates.
3. To compare the incidence of DAS 28 remission and low disease activity state at each visit.
4. To compare effects on all health outcomes measures in the study at each visit, as appropriate for the specific outcome, compared to baseline.

Primary end point(s): Multiple endpoints will be evaluated during the study to meet the stated objectives.
Signs and Symptoms
• ACR20 responder rates analyzed at all timepoints;
• ACR50 and ACR70 responder rates at all timepoints;
• DAS 28-3 and DAS 28-4 (CRP) at all timepoints;
• DAS 28-3 and DAS 28-4 (ESR) at baseline, 3 months, 6 months and 12 months at participating sites (dependent upon availability of a local laboratory that can report ESR results directly to the central laboratory, to ensure blinding of data).
Physical Function and Patient Reported Outcomes
• Assessed at Baseline, Week 2 and Months 1, 2, 3, 4.5, 6, 9, and 12 / Early Termination:
• Health Assessment Questionnaire – Disability Index;
• Patient Assessment of Arthritis Pain;
• Patient Global Assessment of Arthritis;
• Physician Global Assessment of Arthritis.
• Assessed at Baseline, and Months 1, 3, 6, 9, and 12 / Early Termination:
• SF-36 (Version 2, Acute).
• Assessed at Baseline and Months 1, 3, 6, and 12 / Early Termination:
• MOS Sleep Scale;
• FACIT – Fatigue Scale.
• Assessed at Baseline and Months 3, 6, and 12 / Early Termination:
• Euro Qol EQ-5D;
• RA Healthcare Resource Utilization Questionnaire;
• Work Limitations Questionnaire.
Safety Endpoints
All safety data will be summarized descriptively through appropriate data tabulations,
descriptive statistics, and graphical presentations, including:
• Incidence and severity of adverse events;
• Incidence and severity of clinical laboratory abnormalities;
• Summary of changes in physical examination compared to baseline by patient;
• Mean change from baseline in vital signs (blood pressure, heart rate, and temperature) measurements.
Exploratory Endpoints
• Number of days required for a >1 day sequential (2 or more consecutive days) decrease in:
• Patient Assessment of Arthritis Pain;
• Patient Global Assessment of Arthritis.

Secondary ID(s)

A3921046