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

• Register: EUCTR
• Last refreshed on: 6 May 2013
• Main ID: EUCTR2008-007023-26-BG
• Date of registration: 22/05/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: PHASE 3 RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF CP 690,550 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS ON BACKGROUND METHOTREXATE
• Scientific title: PHASE 3 RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF CP 690,550 IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS ON BACKGROUND METHOTREXATE
• Date of first enrolment: 16/06/2009
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007023-26
• 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

Bulgaria, Czech Republic, Poland

Key inclusion & exclusion criteria

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 or antibodies to cyclic citrullinated peptide
2. Be on an adequate and stable dose of methotrexate
3. Meet all eligibility criteria outlined below.
Active RA-Patients must meet all the following criteria:
1. Meet the ACR classification criteria for the diagnosis of RA by satisfying at least four of the seven criteria.
2. Have at least three distinct joint erosions on posteroanterior (PA) hand and wrist or anteroposterior (AP) foot radiographs OR if this is not available, must have a positive IgM rheumatoid factor OR antibodies to cyclic citrullinated peptide
3. The patient must have active disease at both screening and baseline, as defined by having both =6 tender/painful joints on motion, and; =6 swollen joints.
4. At screening must have either Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr or C reactive protein (CRP) >7 mg/L
5. The patient must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
Background Methotrexate:
All local standard of care practices for use of methotrexate, including laboratory testing, follow up care, contraindications, and folic acid administration should be performed throughout the study.
Minimum guidelines for methotrexate and folic acid therapy during study:
1. Must have taken oral or parenteral methotrexate continuously for at least 4 months and be on a stable weekly dose for at least 6 weeks. Weekly doses less than 15 mg are allowed only in the presence of intolerance or toxicity or where higher doses violate the local label. Doses higher than 25 mg weekly are not permitted.
2. Be on a stable dose of folic acid not less than 5 mg weekly, unless higher doses would violate the local label, for at least 4 weeks.
3. Must have an inadequate clinical response to methotrexate defined as the presence of sufficient residual disease activity to meet the entry criteria.
Other Inclusion Criteria:
Patients with a diagnosis of rheumatoid arthritis, on an adequate dose of methotrexate, and must meet the remaining inclusion criteria to be eligible for enrollment into the trial:
1. Evidence of a signed and dated informed consent document
2. Must be at least 18 years of age or older
3. Must discontinue all disallowed concomitant medications for the required time 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 childbearing potential and men whose partners are women of childbearing potential are required to use adequate contraceptive methods during participation in this trial, as required for men and women on methotrexate therapy.
6. 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 Mantoux Purified Protein Derivative skin test result of <5 mm of induration (<20 mm erythema in Japan), within 3 months prior to screening.
•A chest radiograph within 3 months prior to screening without changes suggestive of active TB infection;
•No history of untreated or inadequately treated latent or active TB infection.
If a patient has received an adequ
Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1. Pregnancy or currently lactating.
2. Blood dyscrasias, including confirmed:
a. Hemoglobin <9 g/dL or Hematocrit <30%;
b. White blood cell count <3.0 x 10 to the power of 9/L;
c. Absolute neutrophil count <1.2 x 10 to the power of 9/L;
d. Platelet count <100 x 10to the power of 9/L.
3. Estimated GFR <40 ml/min based on Cockcroft Gault calculation.
4. 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.
5. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, metabolic, pulmonary, cardiac, or neurological disease.
6. History of any other rheumatic autoimmune disease, other than Sjogren’s syndrome
7. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
8. 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.
9. History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
10. 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.
11. History of any infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug.
12. 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.
13. 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.
14. 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.
15. History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug.
16. Screening 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety.
17. A patient with a first degree relative with a hereditary immunodeficiency.
18. 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.
19. Significant trauma or surgery procedure within 1 month prior to first dose of study drug.
20. A patient requiring prohibited concomitant medications including prohibited dietary

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

Health Condition(s) or Problem(s) studied

CP 690,550 is being studied as a disease modifying antirheumatic drug for the treatment of moderate to severe active rheumatoid arthritis in adults.
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: This study is designed to provide pivotal efficacy data in support of the proposed claims of reducing signs and symptoms, inhibiting the progression of structural damage, and improvement in physical function and to provide 2 year safety data for CP-690,550 dosed at 5 and 10 mg BID in patients with inadequate response to stable weekly doses of background methotrexate.
1. For signs & symptoms as measured by ACR20 response rates at Month 6.
2. For evidence of joint structure preservation as measured by changes from baseline using a validated method, such as the van der Heijde modified Sharp score.
3. For physical function status of patients using the HAQ DI at Month 3 compared to baseline.
4. Compare the rate of achieving DAS28-4 (ESR) <2.6 at Month 6 by treatment group.
5. For safety & tolerability.

Secondary Objective: Secondary objectives will compare 5 mg and 10 mg of CP-690,660 BID versus placebo in patients with active RA on stable doses of background methotrexate for:
1. The treatment of signs and symptoms of RA 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. The durability of ACR20, ACR50, and ACR70 and DAS 28 response rates.
3. To compare the incidence of DAS28 <2.6 and DAS28 =3.2 at each visit.
4. Effects on all health outcomes measures in the study at each visit, as appropriate for the specific outcome, compared to baseline.
The study will include the collection of de-identified biological samples. An additional informed consent document is required and the Molecular Profiling Supplement contains further information and details regarding this sampling; participation is optional.

Primary end point(s): Multiple endpoints will be evaluated during the study to meet the stated objectives. Specifically, they are:
Signs & 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 all timepoints 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).

Secondary ID(s)

2008-007023-26-CZ

A3921044