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 METHOTREXATE WITH INADEQUATE RESPONSE TO TNF INHIBITORS

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-014296-40-GB
• Date of registration: 20/10/2010
• Prospective Registration: No
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• 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 METHOTREXATE WITH INADEQUATE RESPONSE TO TNF INHIBITORS
• 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 METHOTREXATE WITH INADEQUATE RESPONSE TO TNF INHIBITORS
• Date of first enrolment: 05/01/2010
• Target sample size: 396
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014296-40
• 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

Austria, Belgium, France, Germany, Ireland, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for inclusion in this study, patients must meet all of these criteria:
1. Active rheumatoid arthritis (RA);
2. Ongoing treatment with an adequate and stable dose of methotrexate;
3. In the opinion of the investigator, at least one approved TNF-inhibiting biologic agent administered in accordance with its labeling recommendations was inadequately
effective and/or not tolerated.
4. All other inclusion criteria.
Active Rheumatoid Arthritis
1. Meet the ACR classification criteria for RA
2. Must have active disease at both screening and baseline, as defined by
having both:
a. =6 tender/painful joints on motion (out of 68 joints assessed); and; b. =6 swollen joints (out of 66 joints assessed).
3. Must also have active disease, as defined by one of the following criteria at screening:
a. Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr; or b. C-reactive protein (CRP) >7 mg/L in the central laboratory.
4. Must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional
Status in RA.
Background Methotrexate
1. Must have taken oral or parenteral methotrexate continuously for at least 4 months prior to the first dose of study medication and be on a stable dose of 7.5 mg to 25 mg weekly, for at least 6 weeks prior to the first dose of study medication. Stable weekly doses less than 15 mg are allowed only in the presence of intolerance to or toxicity from higher doses or where higher doses would violate the local label. Doses higher than 25 mg weekly are not permitted under any circumstances.
2. Patients 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 medication.
1. Evidence of a signed and dated informed consent document.
2. Must be at least 18 years of age.
3. 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 study.
4. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as described in the protocol
5. For traditional DMARDS, the following minimum washout criteria apply:
• Minocycline, Penicillamine, Sulfasalazine: must have been discontinued for 4 weeks prior to the first dose of study drug.
• Leflunomide (Arava®) must have been discontinued 8 weeks prior to the first dose of study drug if no elimination procedure is followed. Alternately, it should have been discontinued with the specified elimination procedure at least 4 weeks prior to the first dose of study drug.
• Auranofin (Ridaura®), Injectable Gold (aurothiglucose or aurothiomalate): must have been discontinued for 8 weeks prior to first dose of study drug.
• Antimalarials (Hydroxychloroquine, Chloroquine): Antimalarials will be allowed in this study. If discontinued, they must be discontinued for 4 weeks prior to the first dose of study drug. If continued, the dose must be stable for at least 8 weeks prior to first dose of study drug.
6. Biologic Response Modifiers. All must be discontinued for entry into this study:
• Anakinra (Kineret®), Enbrel (Etanercept®), Golimumab (Simponi TM):
Discontinued for 4 weeks prior to the first dose of study drug;
• Adalimumab (Humira®): Discontinued for 6 weeks prior to first dose of study
drug;
• Infliximab (Remicade®): Discontinued for 8 weeks prior to the first dose of study
Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1. Any prior treatment with non B lymphocyte-selective lymphocyte depleting agents/therapies, such as alemtuzumab (Campath®) OR alkylating agents (eg, cyclophosphamide or chlorambucil) OR 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.
2. Pregnant or lactating females.
3. Blood dyscrasias including confirmed:
- Hemoglobin <9 g/dL or Hematocrit <30%;
- White blood cell count <3.0 x 10^9/L;
- Absolute neutrophil count <1.2 x 10^9/L;
- Platelet count <100 x 10^9/L.
4. Estimated GFR less than 40 ml/min based on Cockcroft-Gault calculation.
5. AST or ALT more than 1.5 times the upper limit of normal at screening visit.
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 autoimmune rheumatic 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 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. A history of recurrent (more than one episode) herpes zoster, disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
13. A patient who was vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, expects to be vaccinated or exposed to these vaccines during treatment, or during the 6 weeks following discontinuation of study drug. (See Section 4.5.2. for further information regarding avoidance of household contacts who may be vaccinated).
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 substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug.
16. Screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect patient safety or interpretation of study results.
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 major surgery within 1 month of screening visit.
20. A patient requiring prohibited concomitant medications including prohibited dietary supplements. Prohibited concomitant medications must be disco

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 12.0 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-690,550-10
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)

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 RA in subjects with RA on background methotrexate who have had an inadequate response to a TNF inhibitor at all other time points as measured by ACR20, ACR50, ACR70 and DAS 28 response rates.
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.

Main Objective: 1. To compare efficacy of CP 690,550 5 mg BID & 10 mg BID vs placebo for treatment of signs & symptoms of RA, in patients with RA on background MTX who have had an inadequate response (IR) to a TNF-i as measured by ACR20 response rates at M3
2. To compare physical function status of patients with active RA on bkg MTX who have had IR to a TNF-i after administration of CP 690,550 5 mg BID & 10 mg BID vs placebo, as measured by HAQ DI response at M3
3. To compare rate of achieving DAS284(ESR) <2.6 at Month 3 in patients with active RA on bkg MTX who have had IR to a TNF-i after administration of CP-690,550 5 mg BID & 10 mg BID vs placebo
4. To compare the safety and tolerability of CP-690,550, in doses of 5 mg BID and 10 mg BID, vs placebo in patients with RA on background methotrexate who have had an inadequate response to a TNF inhibitor.

Primary end point(s): 1. American College of Rheumatology 20 (ACR20) responder rate versus placebo at the Month 3 visit.
2. Change from baseline in the Health Assessment Questionnaire (HAQ-DI) vs. placebo at the Month 3 visit.
3. Incidence rate for DAS28-4 (ESR) <2.6 versus placebo at the Month 3 visit.

Secondary ID(s)

A3921032

2009-014296-40-DE