| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| JUVENILE IDIOPATHIC ARTHRITIS (JIA) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Juvenile Idiopathic Arthritis (formerly known as Juvenile Rheumatoid Arthritis) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059176 |
| E.1.2 | Term | Juvenile idiopathic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 objective of this study is to determine the long term safety and tolerability of CP 690,550 for treatment of the signs and symptoms of JIA. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of this study is to evaluate the persistence of efficacy of CP 690,550 for treatment of the signs and symptoms of JIA. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Pediatric patients with JIA aged from 2 to less than 18 years who met entry criteria for the qualifying/index study and in the opinion of the investigator have sufficient evidence of RA disease activity to warrant use of CP 690,550 as a DMARD. Patients turning 18 years of age during participation in the qualifying/index study or subsequently will be eligible for participation in this study.
2. The patient has discontinued disallowed concomitant medications for the required time prior to the first dose of study drug, as defined in Appendix 1 of the protocol, and is taking only those concomitant medications in doses and frequency allowed by the protocol.
3. Fertility:
a. Sterile male, or non sterile male. If the patient is a non sterile male on background medications (including DMARDs) that require male contraceptive precautions according to the local drug label and is sexually active with a female partner of child bearing potential, he and his partner must be practicing effective contraceptive measures.
b. Females of childbearing potential must be using a reliable means of contraception (abstinence being a possible option) throughout the study and and for at least one ovulatory cycle after CP 690,550 treatment is discontinued.
4. For patients receiving methotrexate (MTX) treatment, MTX may be administered either orally or parenterally at doses up to the lesser of 20 mg/wk or 15 mg/m2/week.
5. For patients receiving leflunomide treatment, leflunomide may be administered according to the following dosing scheme:
• 10 mg every other day for patients weighing less than 20 kg,
• 10 mg every day for patients weighing between 20 and 40 kg,
• 20 mg every day for patients weighing over 40 kg;
Or as according to local standards.
6. A negative QuantiFERON® TB Gold 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.
7. Evidence of a personally signed and dated informed consent document with assent as appropriate indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
8. Patients who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
For patients who do not roll over into this study within 14 days of their last visit of their qualifying/index study (1 5): 1. Systemic JIA with active systemic features, persistent oligoarthritis, and undifferentiated JIA. 2. Blood dyscrasias, including:
Hgb <10 g/dL or Hct <33%;WBC <3.0 x 10 to the power of 9/L;Neutrophil count <1.2 x 10 to the power of 9/L;Lymphocite count <0.5x10 to the power of 9/L;Platelet count <100 x 10 to the power of 9/L.
3.Estimated GFR <40 mL/min/1.73 m2 calculated using the Schwartz formula at the Screening Visit. 4. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease. 5. AST or ALT ≥1.5 times the upper limit of normal or any other clinically significant laboratory abnormality.
For all patients: 6. History of any other rheumatic autoimmune disease. 7. History or current symptoms suggestive 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. 8. Infections:
a. Latent or active TB or any history of previous TB.
b. Chronic infections.
c. Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug.
d. Any treated infections within 2 weeks.
e. A patient known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.
f. History of infected joint prosthesis with prosthesis still in situ.
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. Patients taking potent and moderate cytochrome P450 3A4 (CYP3A4) inhibitors. 11.Patients taking potent and moderate CYP3A4 inducers. 12. Participation in studies of investigational compounds (excluding qualifying/index study with CP 690,550) within 4 weeks or 5 half lives (whichever is longer) prior to the 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 the Pfizer Medical Monitor. 13. 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. 14. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol during the study and for least one ovulatory cycle after the last dose of study medication.
15. Intramuscular or intravenous corticosteroids in the 4 weeks preceding first dose of study medication. 16.Patients who have been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication. All study participants should be up-to-date with respect to standard of care vaccinations (as defined by their country health ministry). (See Life Style Guidelines of the protocol for further information regarding avoidance of household contacts who may be vaccinated). 17. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. 18. Herbal supplements must be discontinued at least 28 days prior to the first dose of study medication. 19.Patients with a first degree relative with a hereditary immunodeficiency. 20. 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. 21. Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery. 22. Unwilling or unable to comply with the Life Style Guidelines described in this protocol. 23. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the 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. 24. Patients who are relatives of investigational site staff members. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Standard laboratory safety data and adverse event (AE) reports. Body weight, height and Tanner Stages will collected to assess growth and physical development. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary end points consist of 4 items:
1) Standard Lab Safety Data
2) AE assessment
3) body weight and height
4) Tanner Stage
Standard Lab Safety Data is performed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 lab is collected at 6 month intervals. AE assessment is performed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 AE assessment is completed at 6 month intervals. Body weight and height is recorded at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 body weight and height is collected at 6 month intervals. Tanner stage is assessed at Baseline and annually thereafter. |
|
| E.5.2 | Secondary end point(s) |
The following efficacy parameters will be assessed:
• Physician global evaluation of disease activity.
• Number of joints with active arthritis.
• Number of joints with limitation of motion.
• Index of inflammation (C reactive protein [CRP]).
• Juvenile Arthritis Multidimensional Assessment Report (JAMAR).
• Parent’s or child evaluation of overall wellbeing (JAMAR Visual Analog Scale [VAS] component).
• Functional ability (JAMAR).
• Health related quality of life (JAMAR).
• American College of Rheumatology (ACR) pediatric response and flare criteria.
• Inactive disease status parameters. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The Secondary endpoints (section 2.2.2) will be assessed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 the assessments will be completed at 6 month intervals. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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 | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 | No |
| 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 |
| Czech Republic |
| Germany |
| Hungary |
| Italy |
| Poland |
| Russian Federation |
| Serbia |
| Slovakia |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| Pfizer’s intent for this study is to make tofacitinib available to patients for as long as it is tolerated and deemed safe and for at least two years after first global marketing approval of tofacitinib for the treatment of JIA, or development of tofacitinib for JIA is discontinued. The total duration of an individual patient’s participation may vary depending upon when they entered the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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