A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO COMPARE 3 DOSE LEVELS OF CP 690,550 VERSUS PLACEBO, ADMINISTERED ORALLY TWICE DAILY (BID) FOR 6 WEEKS, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-002846-36-DE
• Date of registration: 01/03/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer Pharma GmbH
• Public title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO COMPARE 3 DOSE LEVELS OF CP 690,550 VERSUS PLACEBO, ADMINISTERED ORALLY TWICE DAILY (BID) FOR 6 WEEKS, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS - N/A
• Scientific title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO COMPARE 3 DOSE LEVELS OF CP 690,550 VERSUS PLACEBO, ADMINISTERED ORALLY TWICE DAILY (BID) FOR 6 WEEKS, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS - N/A
• Date of first enrolment: 14/06/2005
• Target sample size: 312
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002846-36
• 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

Germany, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
- The subject can give written informed consent.

- Male or female subjects at least 18 years of age. However, for subjects >70 years old, the site must discuss subject eligibility with the study team to ensure that these subjects are sufficiently healthy to participate.

- If the subject is a sexually active woman of childbearing potential, she and any male partner are required to simultaneously use 2 effective contraceptive methods, one of which must be a barrier (condoms, diaphragm or cervical cap) with spermicide. The other may be an oral or other acceptable contraceptive, which includes, but is not limited to: injectable, implanted or patch hormone therapy, IUD, or documented surgical sterilization for at least 4 weeks before screening, or partner vasectomy. She and any male partner must be willing to continue all of these contraceptive methods for 6 months after receiving study treatment. Within these limits, the specific forms of contraception employed are left to the discretion of the subject, the principal investigator, and/or the subject’s physician.

- Non-vasectomized men must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception such as an IUD, barrier method with spermicide, oral contraceptive, injectable progesterone, sub-dermal implant, or a tubal ligation, if the woman could become pregnant from the time of the first dose of study medication until completion of follow-up procedures.

- The subject has a diagnosis of RA based upon the American College of Rheumatology (ACR; formerly American Rheumatism Association) 1987 Revised Criteria,9 ie, fulfilling at least 4 of the following 7 criteria for at least 6 consecutive months preceding participation:
a. morning stiffness in and around any joint for more than 1 hour;
b. soft tissue swelling of 3 or more joint areas;
c. swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP) or wrist joints;
d. symmetrical joint swelling;
e. rheumatoid nodules;
f. serum rheumatoid factor positive;
g. radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.

- The subject has active disease at both Screening and Baseline, as defined by both:
· =9 joints tender or painful on motion, AND
· =6 joints swollen;
and fulfills 2 of the following 3 criteria at Screening:
· at least 45 minutes duration of morning stiffness,
· at least 28 mm/hour erythrocyte sedimentation rate (ESR) (Westergren method),
· at least 10 mg/L C-reactive protein (CRP).

- The subject meets ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II or III (Appendix A protocol).

- Subjects must have had an inadequate response to, or discontinued for unacceptable toxicity to, either methotrexate, etanercept, infliximab, or adalimumab, according to the following criteria:
· For methotrexate: an inadequate clinical response to doses of at least 15 mg weekly for at least 3 months, unless lower doses can be justified due to documented unacceptable toxicity.
· For etanercept, infliximab, or adalimumab: either inadequate clinical response to an approved dose/regimen for at least 3 months or discontinuation for documented unacceptable toxicity.

- The subject has discontinued all DMARD and immunosuppressive/immunomodulatory therapy for at least 4 weeks prior to first dose of study drug:
· DMARDs: auranofin (oral gold), injectable gold (aurothioglucose or aurothio
Exclusion criteria:
- Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels <10 gm/dL or hematocrit <32% at screening visit or within the 3 months prior to randomization.

- An absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3) at screening visit.

- Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit.

- Estimated GFR= 60 ml/min based on Cockcroft-Gault calculation (Appendix D).

- Pregnant or lactating women.

- Total bilirubin, AST or ALT more than 1.2 times the upper limit of normal at screening visit.

- Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.

- History of an infected joint prosthesis at any time, with the prosthesis still in situ.

- Current immunization with any live virus vaccine (eg, FluMist™) or history of immunization with any live virus vaccine within 1 month of randomization, or during the 6 weeks of treatment and the first 4 weeks of the follow-up period.

- Current routine household contact with children who have received varicella or oral polio vaccine within 2 months of randomization, or during the 6 weeks of treatment and the first 4 weeks of the follow-up period.

- History of any lymphoproliferative disorder (such as EBV-related lymphoproliferative disorder, as reported in some subjects on other immunosuppressive drugs), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease.

- History of previously untreated infection with Mycobacterium tuberculosis (TB) or current treatment for same, as defined by any of the following:
· A positive Mantoux Purified Protein Derivative (PPD) skin test, within the 3 months prior to randomization or
· Chest radiograph, within the 3 months prior to randomization, that has changes suggestive of active TB infection

- Subjects with clinically significant infections currently or within the past 6 months.

- A subject who has received any experimental therapy for RA (within or outside a clinical trial) within 6 months prior to randomizations. However, subjects who have received an experimental NSAID or selective COX-2 inhibitor may participate once they have stopped the experimental therapy for more than 30 days.

- Any prior treatment with lymphocyte-depleting agents/therapies.

- Subjects with any condition possibly affecting oral drug absorption.

- History of alcohol abuse with less than 6 months of sobriety.

- History of drug abuse within 3 years.

- Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect subject safety or interpretation of study results.

- Unwillingness to refrain from consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication until the end of the treatment period.

- Donation of blood in excess of 500 mL within 56 days prior to dosing.

- Subjects with an oral temperature at Baseline visit of 38°C or higher.

- Subjects with a first-degree relative with a hereditary immunodeficiency.

- Subjects with malignancies or with a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

- Recent (within 1 month of screening) significant trauma or major surgery.



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 7.1 Level: LLT Classification code 10039073

Intervention(s)

Product Name: CP690,550
Product Code: CP690,550
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CP690,550
Other descriptive name: (3R,4R)-4-methyl-3-(methyl-1H-pyrrolo [2,3-d]pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile,
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: CP690,550
Product Code: CP690,550
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CP690,550
Other descriptive name: (3R,4R)-4-methyl-3-(methyl-1H-pyrrolo [2,3-d]pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile,
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the efficacy of 3 dose levels of oral CP 690,550 monotherapy (5 mg, 15 mg, and 30 mg twice daily [BID]) versus placebo administered over 6 weeks for the treatment of the signs and symptoms of subjects with active RA.

Primary end point(s): The primary endpoint is the American College of Rheumatology 20 (ACR 20) Responder rate at the Week 6 visit

Secondary Objective: The secondary objectives of this study are:
-To evaluate the safety and tolerability over 12 weeks of CP 690,550 administered for 6 weeks, plus 6 weeks post-dosing follow up, to subjects with active RA.
- To evaluate the pharmacokinetics of CP 690,550 and its correlation with clinical responses and with biomarkers of inflammation and immunosuppression.
- To evaluate health status and functional status.

Secondary ID(s)

A3921019

N/A