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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02592434

Registration number

NCT02592434

Ethics application status

Date submitted

14/08/2015

Date registered

30/10/2015

Titles & IDs

Public title

Efficacy Study Of Tofacitinib In Pediatric JIA Population

Scientific title

EFFICACY, SAFETY AND TOLERABILITY OF TOFACITINIB FOR TREATMENT OF POLYARTICULAR COURSE JUVENILE IDIOPATHIC ARTHRITIS (JIA) IN CHILDREN AND ADOLESCENT SUBJECTS

Secondary ID [1]

2015-001438-46

Secondary ID [2]

A3921104

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Juvenile Idiopathic Arthritis

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Inflammatory and Immune System

Rheumatoid arthritis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - CP-690,550 (tofacitinib)
Other interventions - placebo

Experimental: CP-690,550 - Treatment arm: Tofacitinib tablets or solution, according to subjects' body weights

Placebo comparator: Placebo - Control arm: matching placebo tablets or solution for tofacitinib

Treatment: Drugs: CP-690,550 (tofacitinib)
During the open label run in phase, all subjects will receive active tofacitinib oral tablets or oral solution twice daily (BID) orally, at a dosage based on the subject's body weight as specified below.

During the double blind, placebo controlled phase, subjects will receive either active tofacitinib oral tablets/oral solution or matching placebo oral tablets/oral solution, twice daily (BID), at a dosage specified below.

Body Weight (Dosage in tablet \[BID\] or solution \[BID\]):

5\<7kg (2mg or 2mL); 7\<10kg(2.5mg or 2. mL); 10 \<15kg (3mg or 3mL); 15\<25kg (3.5mg or 3.5mL); 25\<40kg (4mg or 4mL); 40kg (5 mg or 5 ml).

Oral solution (1 mg/mL) is used for subjects \<40 kg. Oral tablets (5 mg) are used for subjects \>=40 kg.

Other interventions: placebo
matching placebo tablet or solution for tofacitinib

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Other interventions

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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

Timepoint [1]

Week 44

Secondary outcome [1]

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 50 Response at Week 44

Timepoint [1]

Week 44

Secondary outcome [2]

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 Response at Week 44

Timepoint [2]

Week 44

Secondary outcome [3]

Double Blind Phase: Percentage of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 70 Response at Week 44

Timepoint [3]

Week 44

Secondary outcome [4]

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

Timepoint [4]

Baseline, Week 44

Secondary outcome [5]

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

Timepoint [5]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [6]

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

Timepoint [6]

Weeks 20, 24, 28, 32, 36 and 40

Secondary outcome [7]

Open-Label Phase: Time to Disease Flare

Timepoint [7]

Day 1 up to week 18

Secondary outcome [8]

Double Blind Phase: Time to Disease Flare

Timepoint [8]

Day 1 of Week 19 up to week 44

Secondary outcome [9]

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

Timepoint [9]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [10]

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

Timepoint [10]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Secondary outcome [11]

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

Timepoint [11]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [12]

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

Timepoint [12]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Secondary outcome [13]

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

Timepoint [13]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [14]

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

Timepoint [14]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36 and 40

Secondary outcome [15]

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

Timepoint [15]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [16]

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

Timepoint [16]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [17]

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

Timepoint [17]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [18]

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

Timepoint [18]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [19]

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

Timepoint [19]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [20]

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

Timepoint [20]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [21]

Open Label Phase: Change From Baseline in JADAS-27 Erythrocyte Sedimentation Rate (ESR) Score at Week 2, 4, 8, 12 and 18

Timepoint [21]

Baseline, weeks 2, 4, 8, 12 and 18

Secondary outcome [22]

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

Timepoint [22]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [23]

Open-Label Phase: Percentage of Participants With JADAS-27 CRP Minimum Disease Activity at Weeks 2, 4, 8, 12 and 18

Timepoint [23]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [24]

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

Timepoint [24]

Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [25]

Open-Label Phase: Percentage of Participants With JADAS-27 CRP Inactive Disease Activity at Week 2, 4, 8, 12 and 18

Timepoint [25]

Weeks 2, 4, 8, 12 and 18

Secondary outcome [26]

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

Timepoint [26]

Double Blind Baseline (Week 18), Week 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [27]

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

Timepoint [27]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [28]

Double Blind Phase: Percentage of Participants With Presence of JIA ACR Clinical Remission

Timepoint [28]

From Week 18 in double blind phase up to Week 44

Secondary outcome [29]

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

Timepoint [29]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [30]

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

Timepoint [30]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [31]

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

Timepoint [31]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [32]

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

Timepoint [32]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [33]

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

Timepoint [33]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [34]

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

Timepoint [34]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [35]

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

Timepoint [35]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [36]

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

Timepoint [36]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [37]

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

Timepoint [37]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [38]

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

Timepoint [38]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, and 40

Secondary outcome [39]

Open-Label Phase: Change From Baseline in Child Health Questionnaire (CHQ) Responses at Week 4 and Week 18

Timepoint [39]

Baseline, Week 4 and Week 18

Secondary outcome [40]

Double Blind Phase: Change From Double-Blind Baseline in Child Health Questionnaire (CHQ) Responses at Week 44

Timepoint [40]

Double-Blind Baseline (Week 18), Week 44

Secondary outcome [41]

Open Label Phase: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ)- Discomfort Index at Weeks 2, 4, 8, 12 and 18

Timepoint [41]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [42]

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

Timepoint [42]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36,40 and 44

Secondary outcome [43]

Open-Label Phase: Percentage of Participants With Active Uveitis at Baseline

Timepoint [43]

Baseline

Secondary outcome [44]

Double Blind Phase: Percentage of Participants With Active Uveitis at Week 24 and Week 44

Timepoint [44]

Week 24 and Week 44

Secondary outcome [45]

Open-Label Phase: Change From Baseline in the Tender Entheseal Assessment at Weeks 2, 4, 8, 12 and 18

Timepoint [45]

Baseline, weeks 2, 4, 8, 12 and 18

Secondary outcome [46]

Double Blind Phase: Change From Double-Blind Baseline in the Tender Entheseal Assessment at Weeks 20, 24, 28, 32, 36, 40 and 44

Timepoint [46]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [47]

Open-Label Phase: Change From Baseline in the Modified Schober's Test at Week 2, 4, 8, 12 and 18

Timepoint [47]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [48]

Double Blind Phase: Change From Double Blind Baseline in the Modified Schober's Test at Week 20, 24, 28, 32, 36, 40 and 44

Timepoint [48]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [49]

Open-Label Phase: Change From Baseline in the Overall Back Pain and Nocturnal Back Pain Responses at Week 2, 4, 8, 12 and 18

Timepoint [49]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [50]

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

Timepoint [50]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [51]

Open-Label Phase: Changes From Baseline in Percentage of Body Surface Area (BSA) Affected With Psoriasis at Weeks 2, 4, 8, 12 and 18

Timepoint [51]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [52]

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

Timepoint [52]

Double Blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [53]

Open-Label Phase: Changes From Baseline in Physician's Global Assessment (PGA) of Psoriasis Assessments at Weeks 2, 4, 8, 12 and 18

Timepoint [53]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [54]

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

Timepoint [54]

Double blind Baseline (Week 18), Weeks 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [55]

Open-Label Phase: Taste Assessment of Tofacitinib Oral Solution on Day 14

Timepoint [55]

Day 14

Secondary outcome [56]

Open-Label Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

Timepoint [56]

From the first dose of study drug up to Week 18

Secondary outcome [57]

Double Blind Phase: Number of Participants With Serious Infections, Cytopenia, Malignancies and Cardiovascular Diseases

Timepoint [57]

From the first dose of study drug in double blind up to week 44

Secondary outcome [58]

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)

Timepoint [58]

Day 1

Secondary outcome [59]

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Pubic Hair)

Timepoint [59]

Week 44

Secondary outcome [60]

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)

Timepoint [60]

Day 1

Secondary outcome [61]

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Breast Exam)

Timepoint [61]

Week 44

Secondary outcome [62]

Open-Label Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)

Timepoint [62]

Day 1

Secondary outcome [63]

Double Blind Phase: Number of Participants With Tanner Staging Evaluation (Genitalia)

Timepoint [63]

Week 44

Secondary outcome [64]

Open-Label Phase: Number of Participants With Laboratory Abnormalities

Timepoint [64]

From the first dose of study drug up to Week 18

Secondary outcome [65]

Double Blind Phase: Number of Participants With Laboratory Abnormalities

Timepoint [65]

From the first dose of study drug in double blind up to Week 44

Secondary outcome [66]

Open-Label Phase: Number of Participants With Physical Examination Abnormalities

Timepoint [66]

Baseline, Weeks 2, 4, 8, 12 and 18

Secondary outcome [67]

Double Blind Phase: Number of Participants With Physical Examination Abnormalities

Timepoint [67]

Weeks 18, 20, 24, 28, 32, 36, 40 and 44

Secondary outcome [68]

Open-Label Phase: Number of Participants With Vital Sign Abnormalities

Timepoint [68]

From the first dose of study drug up to Week 18

Secondary outcome [69]

Double Blind Phase: Number of Participants With Vital Sign Abnormalities

Timepoint [69]

From the first dose of study drug in double blind up to week 44

Secondary outcome [70]

Open-Label Phase: Number of Participants With Change From Baseline in Vital Sign Measures

Timepoint [70]

From the first dose of study drug up to Week 18

Secondary outcome [71]

Double Blind Phase: Number of Participants With Change From Baseline in Vital Sign Measures

Timepoint [71]

From the first dose of study drug in double blind up to week 44

Eligibility

Key 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.

Minimum age

2 Years

Maximum age

17 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

10/06/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

16/05/2019

Sample size

Target

Accrual to date

Final

225

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

The Sydney Children's Hospital Network Westmead - Westmead

Recruitment hospital [2]

The Royal Children's Hospital - Parkville

Recruitment postcode(s) [1]

2145 - Westmead

Recruitment postcode(s) [2]

3052 - Parkville

Recruitment outside Australia

Country [1]

United States of America

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Hampshire

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United Kingdom

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WEST Midlands

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Pfizer

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Ethics application status

Summary

Brief summary

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

Trial website

https://clinicaltrials.gov/study/NCT02592434

Trial related presentations / publications

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.

Public notes

Contacts

Principal investigator

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Pfizer CT.gov Call Center

Address

Pfizer

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Address

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Fax

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

When will data be available (start and end dates)?

Available to whom?

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/34/NCT02592434/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/34/NCT02592434/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02592434

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For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02592434