| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to determine the long term safety and tolerability of 5 mg BID and 10 mg BID of CP-690,550 for treatment of the signs and symptoms of RA. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the persistence of efficacy of 5 mg BID and 10 mg BID of CP-690,550 for treatment of the signs and symptoms of RA.
Exploratory
The first exploratory objective of this study is to analyze HAQ-DI score data to model healthcare utilization over the long-term in patients taking CP-690,550.The second exploratory objective of this study is to analyze the long-term effects of CP-690,550 on the rate and risk of progression of structural damage in patients with RA who had baseline radiographs obtained in their qualifying index study. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients who enroll from an index study within a 14-day window must meet Inclusion
Criteria 1, 2, 4, 6, 7 and 8 below and must continue to meet the safety eligibility criteria of their index study for continued participation. Patients who enroll after the 14-day window must meet all Inclusion Criteria including Inclusion Criteria 3 and 5 to be eligible for enrollment into the trial.
1. 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 trial.
2. Patient must be at least the legally recognized age of consent or provide assent in writing along with a consent signed by their legally recognized representative.
3. In the opinion of the investigator the patient must have sufficient evidence of RA disease activity to warrant use of CP-690,550 as a DMARD.
4. Patients must have previously completed participation in a randomized qualifying study of CP-690,550 for the treatment of RA or have required earlier discontinuation of treatment in a randomized qualifying study for reasons other than CP-690,550 related serious adverse events with the approval of the Pfizer study clinician.
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-Gold®TM In-Tube test performed within the 3 months
prior to screening. A negative PPD test can be substituted for the QuantiFERON®-TB Gold In-Tube test only if the central laboratory is unable to perform the test or cannot determine the results to be positive or negative and the Pfizer Medical Monitor approves it, on a case-by-case basis;
- A chest radiograph taken within the 3 months prior to screening without changes
suggestive of active TB infection;
- No history of either untreated or inadequately treated latent or active TB infection.
If a patient has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug resistant TB infection are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a PPD test nor a QuantiFERON-Gold®TM test need be obtained, but a chest radiograph must still be obtained if not done so within the prior 3 months. A patient who is currently being treated for either latent or active TB infection can only be enrolled with confirmation of current incidence rates of multi-drug resistant TB infection, documentation of an adequate treatment regimen, and prior approval of the Sponsor. In Ireland, patients currently being treated for either latent or active TB infection can not be enrolled.
6. The patient has discontinued disallowed concomitant medications for the required time prior to the first dose of study drug, as defined in Appendix A, and is taking only those concomitant medications in doses and frequency allowed by the protocol.
7. If the patient is a sexually active woman of childbearing potential, she must test negative for pregnancy prior to enrollment in this study. Sexually active women of childbearing potential are required to use adequate contraceptive methods during participation in this study. Men who are on background therapy and whose partners are women of childbearing potential will be required to follow the local label requirements for their background medications (including background DMARDS). Further description of the requirements and a list of contraceptives considered effective and acceptable for use in this study will be found in Lifestyle Guidelines
8. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. |
|
| E.4 | Principal exclusion criteria |
For patients who do not rollover into this study within 14 days of their last visit of index study(1-5):
1.Evidence of hematopoietic disorders or evidence of hemoglobin levels <9 gm/dL or hematocrit <30% at screening visit or within the 3 mths prior to baseline visit.
2.An absolute white blood cell (WBC) count of <3.0x10 to the power of 9/L <3000/mm3) or absolute neutrophil count of <1.2x10 to the power of 9/L (<1200/mm3) at screening visit or within 3 months prior to baseline.
3.Thrombocytopenia as defined by a platelet count <100x10 to the power of 9/L (<100,000/mm3) at screening visit or within 3 mths prior to baseline.
4.Estimated creatinine clearance <40 mL/hr by Cockroft Gault equation at screening visit.
5.Total bilirubin, AST or ALT more than 1.5 times upper limit of normal at screening visit. For all patients:
6.Pregnant or lactating women.
7.Current or recent history of uncontrolled clinically significant renal, hepatic, hematological,gastro-intestinal,endocrine,pulmonary,cardiac, or neurological disease.
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 such as Epstein Barr Virus related lymphoproliferative disorder,history of lymphoma,leukemia, or signs and symptoms suggestive of current lymphatic disease.
11.History of recurrent(more than 1 episode)herpes zoster or disseminated(a single episode) herpes zoster or disseminated(a single episode)herpes simplex.
12.Patients with any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by investigator within the 6 mths prior to the first dose of study drug.
13.Any other condition which would make patient unsuitable for inclusion in the study.
14.Participation in studies of investigational compounds(except CP-690,550)within 4 wks or 5 half-lives(which ever is longer)prior to first dose of study drug. Patients cannot participate in studies of other investigational compounds at any time during their participation in this study. Exposure to investigational biologics should be discussed with Pfizer Medical Monitor.
15.Any prior treatment with non B cell-specific lymphocyte depleting agents/ therapies [eg, almetuzumab(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.
16.Intramuscular or intravenous corticosteroids in the 4 wks preceding baseline. If an intra-articular injection is performed in the course of a qualifying study <4 wks before baseline visit of this study, the injected joint will be considered to have its pre-injection status from the index study for full length of this protocol.
17.Patients who have been vaccinated with live or attenuated vaccines within 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.
18.Patients with any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy or certain types of bariatric surgery such as gastric bypass. Bariatric procedures such as gastric banding that simply divide stomach into separate chambers are NOT exclusionary. 19.History of alcohol or substance abuse, unless in full remission for >6 months prior to first dose of study drug.
20.Screening 12 lead electrocardiogram that demonstrates clinically relevant abnormalities that may affect patient safety.
21.Patients with a first degree relative with a hereditary immunodeficiency.
22.Patients 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.
23.Recent(within 1 month prior to first dose of study drug)significant trauma or major surgery.
24.Patients requiring prohibited concomitant medications. Patients receiving non prohibited concomitant medications must be on a stable regimen which is defined as not starting a new drug or changing dosage within 7days or 5half lives(whichever is longer)prior to the baseline visit.
25.Patients known to be infected with human immunodeficiency virus(HIV) or Hepatitis B or C virus.
26.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary endpoints will be standard laboratory safety data (chemistry, hematology, etc.) and adverse event (AE) reports. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 177 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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