Clinical trial NCT02592434: Efficacy Study Of Tofacitinib In Pediatric JIA Population
Official title: EFFICACY, SAFETY AND TOLERABILITY OF TOFACITINIB FOR TREATMENT OF POLYARTICULAR COURSE JUVENILE IDIOPATHIC ARTHRITIS (JIA) IN CHILDREN AND ADOLESCENT SUBJECTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Idiopathic Arthritis
Keywords: Arthritis
Pediatric
Long-term
JIA
polyarticular
CP-690,550
tofacitinib
Xeljanz
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 225
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate efficacy, safety and tolerability of tofacitinib in pediatric JIA patients.

Detailed description: This is a randomized withdrawal, double blind, placebo controlled study of pediatric subjects (2 to \<18 years of age) with JIA. The primary objective is to compare the efficacy of tofacitinib versus placebo for the treatment of signs and symptoms of JIA at Week 26 of the double blind phase as measured by the percentage of subjects with disease flare (according to PRCSG/PRINTO Disease Flare criteria) after Week 18 of the open label run in phase.All eligible subjects enrolled in the study will initially receive open label tofacitinib for 18 weeks (run in phase). At the end of the 18 week run in phase, only subjects who achieve at least a JIA ACR 30 response will be randomized to the 26 week double blind, placebo controlled phase. Subjects who do not achieve a JIA ACR 30 response at this time point will be discontinued from the study. In addition, subjects who experience a single episode of disease flare at any time during the study (including the open label run in and double blind phase) will also be discontinued from the study. All subjects participating in this study, including those discontinued from the study, will have the option, if eligible (based on inclusion and exclusion criteria), of enrolling in the tofacitinib JIA long term extension study (A3921145).

Subjects who are eligible for the 26 week double blind phase will be randomized (1:1 ratio) to either active tofacitinib or placebo. For subjects with polyarticular course JIA (ie, extended oligoarthritis, polyarthritis RF+, polyarthritis RF , systemic JIA with active arthritis but without active systemic features), randomization will be stratified by JIA category and baseline CRP (normal, above normal). For subjects with psoriatic and enthesitis related arthritis, randomization will be stratified by JIA category.

Approximately 210 subjects will be enrolled in the open label run in phase. Among subjects with polyarticular course JIA, stratification will target at least 50% with a baseline CRP above the upper limit of normal. The first cohort (ie, polyarticular course JIA) will have at least 170 subjects enrolled in the run in phase with the minimum number of JIA categories as follows: 24 with extended oligoarthritis, 20 with polyarthritis RF+, 62 with polyarthritis RF-, and no minimum for subjects with systemic JIA with active arthritis but without active systemic features. Additional cohorts (ie, psoriatic and enthesitis related arthritis) will include a minimum of 20 subjects with psoriatic arthritis, and 20 subjects with enthesitis related arthritis. The overall target minimum number of subjects to be enrolled in the study by age is as follows: 20 subjects 2 to \<6 years, 20 subjects 6 to \<12 years, and 20 subjects 12 to \<18 years. The duration of subject participation among those who complete the study (without discontinuation) is expected to be approximately 44 weeks.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged 2 to \<18 years.
2. Must meet International League Against Rheumatism (ILAR) JIA diagnostic criteria for one of the following categories with active disease for at least 6 weeks:

   * Extended oligoarthritis;
   * Polyarthritis (RF+);
   * Polyarthritis (RF-);
   * Systemic JIA with active arthritis but without active systemic features in the prior 6 months and at the time of enrollment;
   * Psoriatic arthritis;
   * Enthesitis related arthritis. Subjects with polyarticular course JIA (ie, extended oligoarthritis, polyarthritis RF+, polyarthritis RF , systemic JIA with active arthritis but without active systemic features) must have a minimum of 5 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry.

   Subjects with psoriatic or enthesitis related arthritis must have a minimum of 3 active joints (an active joint is defined as a joint with swelling or, in the absence of swelling, limited range of motion accompanied by either pain on motion or tenderness) at screening and baseline to be eligible for study entry.

   Treatment with stable doses of a Non Steroidal Anti inflammatory Drug (NSAID) and/or a stable dose of an oral glucocorticoid, and/or a stable dose of methotrexate is permitted.

   For subjects receiving an oral glucocorticoid: Glucocorticoids may be administered at a maximum dose of 0.2 mg of prednisone equivalent per kilogram per day or 10 mg per day for ≥ 2 weeks before baseline, whichever is lower.

   For subjects receiving methotrexate (MTX) treatment: MTX may be administered either orally or parenterally at doses not to exceed 25 mg/wk or 20 mg/m2/week (whichever is lower); participants must have taken MTX for 3 months and be at a stable dose for at least 6 weeks before baseline. Subjects taking MTX must be taking folic acid or folinic acid in accordance with local standards.

   For subjects with psoriatic arthritis, the following topical treatments for psoriasis are allowed: non medicated emollients for use over the whole body; topical steroids including hydrocortisone and hydrocortisone acetate ≤1% for the palms, soles, face, and intertriginous areas only; tar, salicylic acid preparations, and shampoos free of corticosteroids are permitted only for the scalp
3. Inadequate response or intolerance to at least one Disease Modifying Anti Rheumatic Drug (DMARD), which may include MTX or biologic agents; in the case of ERA and psoriatic arthritis, inadequate response to Non Steroidal Anti Inflammatory Drugs (NSAIDs).
4. No evidence or history of untreated or inadequately treated active or latent tuberculosis (TB) infection as evidenced by the following:

   1. A negative QuantiFERON ®TB Gold In Tube test performed within the 3 months prior to screening. A negative purified protein derivative (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 is informed and agrees on a case by case basis.
   2. Chest radiograph without changes suggestive of active tuberculosis (TB) infection within 3 months prior to screening is recommended and should be performed according to local standards of care or country-specific guidelines.
   3. No history of either untreated or inadequately treated latent or active TB infection.

   If a subject 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. A chest radiograph should be obtained if not done within the 3 months prior to screening. To be considered eligible for the study, the chest radiograph must be negative for active tuberculosis infection.

   A subject who is currently being treated for latent 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.
5. Fertile males and females who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be willing and able to use a highly effective method of contraception as outlined in this protocol during the study and for at least 28 days after the last dose of study medication.

6 Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

7. Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study.

Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the study:

1. Previous JIA treatment with tofacitinib.
2. Systemic JIA (sJIA) with active systemic features (including subjects with characteristic sJIA fever and rash or serositis within 6 months of enrollment).
3. Persistent oligoarthritis.
4. Undifferentiated JIA.
5. Infections:

   1. Chronic infections;
   2. 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;
   3. Any treated infections within 2 weeks of Baseline visit;
   4. A subject know to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C;
   5. History of infected joint prosthesis with prosthesis still in situ.
6. History of recurrent (more than one episode) herpes zoster or disseminated (at least one episode) herpes zoster, or disseminated (at least one episode) herpes simplex.
7. Active uveitis (according to SUN criteria) within 3 months of enrollment.
8. Blood dyscrasias, including:

   1. Hemoglobin \<10 g/dL or Hematocrit \<33%;
   2. White Blood Cell count \<3.0 x 109/L;
   3. Neutrophil count \<1.2 x 109/L;
   4. Platelet count \<100 x 109/L;
   5. Lymphocyte count \<0.75 x 109/L.
9. Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 at Screening. GFR will be calculated by the central lab using the bedside Schwartz formula.
10. Current or recent history of uncontrolled clinically significant renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
11. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1.5 times the upper limit of normal.
12. History of any other rheumatologic disease, other than Sjogren's syndrome..
13. History or current symptoms suggestive of lymphoproliferative disorders (eg, Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, or signs and symptoms of current lymphatic disease).
14. Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of study drug.
15. Subjects without documented evidence of having received at least one dose of the varicella vaccine in countries where the vaccine is approved and standard of care or those who do not have evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (ie, VZV IgG Ab).
16. Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ.
17. Subjects who have previously failed more than 3 biologic therapies (with different mechanisms of action) for JIA.
18. Subjects with a first degree relative with a hereditary immunodeficiency; IgA deficiency not exclusionary.
19. Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery.
20. Subjects receiving potent and moderate CYP3A4 inhibitors or inducers.
21. Prior treatment with non B cell specific lymphocyte depleting agents/therapies (eg, almetuzumab \[CAMPATH\], alkylating agents \[eg, cyclophosphamide or chlorambucil\], total lymphoid irradiation, etc.). Subjects 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.
22. Use of prohibited prescription or non prescription drugs and dietary supplements listed in Appendix 1 and Appendix 4 within the specified time frame prior to the first dose of study medication.
23. Herbal supplements must be discontinued at least 28 days prior to the first dose of study medication.
24. Use of certain biologic and non biologic DMARDs are disallowed at any time during this study (Appendix 1).
25. For subjects with PsA, oral and topical medications and alternative treatments that could affect psoriasis are prohibited (see Inclusion Criterion 2 for exceptions). This includes topical corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids which must be discontinued at least 2 weeks prior to first dose of study drug. Also prohibited is ultraviolet B (UVB) (narrowband or broadband) phototherapy that must be discontinued at least 2 weeks prior to first dose of study drug. Psoralens + ultraviolet A (UVA) phototherapy (PUVA) must be discontinued at least 4 weeks prior to first dose of study drug.
26. Subjects who are children of or related to investigational site staff members, site staff members otherwise supervised by the investigator, or Pfizer employees directly involved in the conduct of the study.
27. Participation in other studies involving investigational drug(s) within 4 weeks or 5 half lives (whichever is longer) prior to study entry and/or during study participation. Exposure to investigational biologics should be discussed with the Sponsor.
28. 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 subject inappropriate for entry into this study.
29. Pregnant or nursing females are excluded.

Primary outcomes:
measure: Double Blind Phase: Percentage of Participants With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 44
timeFrame: Week 44
Secondary outcomes:
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44
timeFrame: Week 44
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44
timeFrame: Week 44
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44
timeFrame: Week 44
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Score at Week 44
timeFrame: Baseline, Week 44
measure: Open-Label Phase: Percentage of Participants With Disease Flare According to Pediatric Rheumatology Collaborative Study Group/Pediatric Rheumatology International Trials Organization (PRCSG/PRINTO) Disease Flare Criteria at Week 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Disease Flare According to PRCSG/PRINTO Disease Flare Criteria at Week 20, 24, 28, 32, 36 and 40
timeFrame: Weeks 20, 24, 28, 32, 36 and 40
measure: Open-Label Phase: Time to Disease Flare
timeFrame: Day 1 up to week 18
measure: Double Blind Phase: Time to Disease Flare
timeFrame: Day 1 of Week 19 up to week 44
measure: Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Weeks 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Double Blind Baseline, Weeks 20, 24, 28, 32, 36 and 40
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40
measure: Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Weeks 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Double Blind Baseline, Weeks 20, 24, 28, 32, 36 and 40
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40
measure: Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Weeks 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Double Blind Baseline (Week 18),Week 20, 24, 28, 32, 36 and 40
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40
measure: Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Week 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 90 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Week 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 100 Response at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: Change From Baseline in Juvenile Arthritis Disease Activity Score 27 (JADAS-27) C-Reactive Protein (CRP) Score at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Change From Double-Blind Baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27 C-Reactive Protein (CRP) Score at Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18
timeFrame: Baseline, weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Change From Double-Blind Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Percentage of Participants With JADAS-27 CRP Minimum Disease Activity at Weeks 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With JADAS-27 CRP Minimum Disease Activity at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Percentage of Participants With JADAS-27 CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18
timeFrame: Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Percentage of Participants With JADAS-27 CRP Inactive Disease Activity at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
measure: Double Blind Phase: Percentage of Participants With JIA ACR Inactive Disease at Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Double Blind Phase: Percentage of Participants With Presence of JIA ACR Clinical Remission
timeFrame: From Week 18 in double blind phase up to Week 44
measure: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Active Arthritis at Week 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Active Arthritis at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Number of Joints With Limited Range of Motion at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Number of Joints With Limited Range of Motion at Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Physician Global Evaluation of Disease Activity at Week 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Physician Global Evaluation of Disease Activity at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Parent/Legal Guardian/Participant Global Evaluation of Overall Well-Being at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open Label Phase: JIA ACR Core Variable- Change From Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Scores at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: JIA ACR Core Variable- Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) Total Scores at Weeks 20, 24, 28, 32, 36, and 40
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, and 40
measure: Open-Label Phase: Change From Baseline in Child Health Questionnaire (CHQ) Responses at Week 4 and Week 18
timeFrame: Baseline, Week 4 and Week 18
measure: Double Blind Phase: Change From Double-Blind Baseline in Child Health Questionnaire (CHQ) Responses at Week 44
timeFrame: Double-Blind Baseline (Week 18), Week 44
measure: Open Label Phase: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase:Change From Double-Blind Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36,40 and 44
measure: Open-Label Phase: Percentage of Participants With Active Uveitis at Baseline
timeFrame: Baseline
measure: Double Blind Phase: Percentage of Participants With Active Uveitis at Week 24 and Week 44
timeFrame: Week 24 and Week 44
measure: Open-Label Phase: Change From Baseline in the Tender Entheseal Assessment at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Change From Double-Blind Baseline in the Tender Entheseal Assessment at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Change From Baseline in the Modified Schober's Test at Week 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Change From Double Blind Baseline in the Modified Schober's Test at Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Change From Baseline in the Overall Back Pain and Nocturnal Back Pain Responses at Week 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Change From Double-Blind Baseline in the Overall Back Pain and Nocturnal Back Pain Responses at Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Changes From Baseline in Percentage of Body Surface Area (BSA) Affected With Psoriasis at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Changes From Double Blind Baseline in Body Surface Area (BSA) Affected With Psoriasis at Week 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Changes From Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Weeks 2, 4, 8, 12 and 18
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase:Change From Double-Blind Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Weeks 20, 24, 28, 32, 36, 40 and 44
timeFrame: Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Taste Assessment of Tofacitinib Oral Solution on Day 14
timeFrame: Day 14
measure: Open-Label Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases
timeFrame: From the first dose of study drug up to Week 18
measure: Double Blind Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases
timeFrame: From the first dose of study drug in double blind up to week 44
measure: Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)
timeFrame: Day 1
measure: Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)
timeFrame: Week 44
measure: Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)
timeFrame: Day 1
measure: Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)
timeFrame: Week 44
measure: Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)
timeFrame: Day 1
measure: Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)
timeFrame: Week 44
measure: Open-Label Phase: Number of Participants With Laboratory Abnormalities
timeFrame: From the first dose of study drug up to Week 18
measure: Double Blind Phase: Number of Participants With Laboratory Abnormalities
timeFrame: From the first dose of study drug in double blind up to Week 44
measure: Open-Label Phase: Number of Participants With Physical Examination Abnormalities
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 18
measure: Double Blind Phase: Number of Participants With Physical Examination Abnormalities
timeFrame: Weeks 18, 20, 24, 28, 32, 36, 40 and 44
measure: Open-Label Phase: Number of Participants With Vital Sign Abnormalities
timeFrame: From the first dose of study drug up to Week 18
measure: Double Blind Phase: Number of Participants With Vital Sign Abnormalities
timeFrame: From the first dose of study drug in double blind up to week 44
measure: Open-Label Phase: Number of Participants With Change From Baseline in Vital Sign Measures
timeFrame: From the first dose of study drug up to Week 18
measure: Double Blind Phase: Number of Participants With Change From Baseline in Vital Sign Measures
timeFrame: From the first dose of study drug in double blind up to week 44
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital - Attention: Jill Hernandez
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Clinical Trial Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Eye Institute
state: California
city: Loma Linda
country: United States
facility: Loma Linda University General Pediatric Clinic - Meridian
state: California
city: Loma Linda
country: United States
facility: Pediatric Specialty Team Centers of LLU Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Bernardino
country: United States
facility: Pediatric Specialty Team Centers of LU Children's Hospital
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital Center for Pediatric Clinical Research
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital Education and Office Building
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital Research Pharmacy
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital Rheumatology Clinic
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center -Pharmacy
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: IDS Pharmacy Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta-Pediatric Research Center
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Children's Specialty Services
state: Georgia
city: Augusta
country: United States
facility: Augusta University Health Pharmacy
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Investigational Drug Services
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children at IU Health
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center Floating Hospital for Children
state: Massachusetts
city: Minneapolis
country: United States
facility: Journey Clinic: Center for Children with Cancer and Blood Diseases, Uni. of Minnesota Medical Centre
state: Minnesota
city: Minneapolis
country: United States
facility: Pediatric Specialty Care Explorer Clinic, University of Minnesota, Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview IDS Pharmacy
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Pharmacy Department
state: New York
city: Lake Success
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: Charlotte
country: United States
facility: Children's Specialty Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System IDS Pharmacy
state: North Carolina
city: Charlotte
country: United States
facility: Pediatric Research
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Medical Center - Inpatient Pharmacy
state: Oregon
city: Portland
country: United States
facility: Randall Children's Hospital at Legacy Emanuel
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Austin
country: United States
facility: Specially for Children, Dell Children's Medical Center of Central Texas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Clinical Care center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Clinical Research Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Investigational Pharmacy
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Main Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital/Baylor College of Medicine - Feigin Center
state: Texas
city: Salt Lake City
country: United States
facility: PCH Pharmacy - Primary Children's Hospital - Pharmacy
state: Utah
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Rosario
country: Argentina
facility: Instituto CAICI SRL
state: Santa FE
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucuman
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Westmead
country: Australia
facility: The Sydney Children's Hospital Network Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven-Gasthuisberg
city: Salvador
country: Brazil
facility: SER - Servicos Especializados em Reumatologia
state: Bahia
city: Juiz de Fora
country: Brazil
facility: CMIP -Centro Mineiro de Pesquisa Ltda / Reumatocenter
state: MG
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe / A ssociacao Hospitalar de Protecao a Infancia
state: Parana
city: Curitiba
country: Brazil
facility: Instituto de Pesquisa Pele Pequeno Principe
state: Parana
city: Rio de Janeiro
country: Brazil
facility: Instituto de Puericultura e Pediatria Martagao Gesteira
state: RJ
city: Botucatu
country: Brazil
facility: Faculdade de Medicina da UNESP
state: SAO Paulo
city: Sao Paulo
country: Brazil
facility: SPDM- Associacao Paulista para o Desenvolvimento da Medicina-Hospital Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca do Hospital das Clinicas da FMUSP
city: Calgary
country: Canada
facility: Alberta Children's Hospital - Inpatient Pharmacy
state: Alberta
city: Calgary
country: Canada
facility: Alberta Children's Hospital/University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Health Centre of B.C.
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Montreal
country: Canada
facility: McGill University Health Canter, Glen site, Pharmacy
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center, Glen Site, Center for Innovative Medicine
state: Quebec
city: Haifa
country: Israel
facility: Rambam Health Care
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba M.C Tel hashomer
city: Guadalajara
country: Mexico
facility: Clinica de Investigacion en Reumatologia y Obesidad, S.C.
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
city: San Luis Potosi
country: Mexico
facility: Sociedad de Beneficencia Espanola, A.C.
city: San Luis Potosi
country: Mexico
facility: Hospital Central "Dr. Ignacio Morones Prieto"
city: San Luis Potosi
country: Mexico
facility: Unidad de Investigaciones Reumatologicas A.C.
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Dzieciecy im. J. Brudzinskiego
city: Moscow
country: Russian Federation
facility: FSAEI HE I.M. Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University)
city: Moscow
country: Russian Federation
facility: FSAEI HE I.M Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University)
city: Moscow
country: Russian Federation
facility: FSAI "NSPCCH" of Minzdrav of Russia
city: Saint-Petersburg
country: Russian Federation
facility: FSBEI HE "St. Petersburg State Pediatric Medical University"
city: Tolyatti
country: Russian Federation
facility: State Budgetary Healthcare Institution of Samara Region "Tolyatti City Clinical Hospital #5"
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
city: Kayseri
country: Turkey
facility: Erciyes University Medical Faculty
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Children's Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Children's Clinical Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Birmingham
country: United Kingdom
facility: Birmingham Woman's and Children's NHS Foundation Trust
state: WEST Midlands
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ruperto N, Brunner HI, Synoverska O, Ting TV, Mendoza CA, Spindler A, Vyzhga Y, Marzan K, Grebenkina L, Tirosh I, Imundo L, Jerath R, Kingsbury DJ, Sozeri B, Vora SS, Prahalad S, Zholobova E, Butbul Aviel Y, Chasnyk V, Lerman M, Nanda K, Schmeling H, Tory H, Uziel Y, Viola DO, Posner HB, Kanik KS, Wouters A, Chang C, Zhang R, Lazariciu I, Hsu MA, Suehiro RM, Martini A, Lovell DJ; Paediatric Rheumatology International Trials Organisation (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG). Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet. 2021 Nov 27;398(10315):1984-1996. doi: 10.1016/S0140-6736(21)01255-1. Epub 2021 Nov 9.