A Long-Term, Open-Label, Study for Treatment of JIA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Apr 2013 → 12 Feb 2025

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-509651-14-00

EudraCT number

2011-004915-22

ClinicalTrials.gov

NCT01513902

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Pharmacokinetic

The primary objective of this study is to determine the long term safety and tolerability of tofacitinib for treatment of the signs and symptoms of JIA.

Secondary objectives 1

1. The secondary objective of this study is to evaluate the persistence of efficacy of tofacitinib for treatment of the signs and symptoms of JIA.

Conditions and MedDRA coding

Juvenile Idiopathic Arthritis (JIA)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. JIA subjects aged 2 to <18 years who met entry criteria for qualifying/index study with sufficient JIA disease activity to use tofacitinib.
2. Discontinuation of disallowed concomitant medications for the required time prior to first dose of study drug and only taking concomitant medications in allowable doses/frequencies.
3. Fertile male and female subjects of childbearing potential who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be using a highly effective method of contraception throughout the study and for at least 28 days after the last dose of study drug.
4. Previously completed participation in a qualifying JIA study of tofacitinib.
5. If receiving MTX, use of MTX orally or parenterally at doses not to exceed 25 mg/week or 20 mg/m2/week, whichever is lower. Must also take folic acid/folinic acid in accordance with local standards.
6. If receiving an oral glucocorticoid, use of glucocorticoids at a max dose of 0.20 mg/kg/day or 10 mg/day, prednisone or equivalent, whichever is lower. For A3921165 subjects, a higher prednisone equivalent dose may be continued or started
7. If receiving leflunomide treatment, use of leflunomide at the following doses: 10 mg every other day for subjects weighing 40 kg; Or as according to local standards.
8. If receiving sulfasalazine, chloroquine, or hydroxychloroquine treatment, administer according to local standards.
9. Evidence of a personally signed/dated ICD with assent as appropriate indicating that the subject (or a legally acceptable representative/parent(s)/legal guardian) has been informed of all aspects of the study.
10. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
11. Subjects for whom, in the Investigator's opinion, treatment with tofacitinib is considered clinically appropriate. Subjects who enroll outside the 14 day window of the EOS Visit of their qualifying/index study must also meet the below:
12. No evidence of active tuberculosis (TB) or inadequately treated tuberculosis (TB) infection (active or latent) as defined in the protocol.

Exclusion criteria 20

1. For subjects who enroll outside the 14 day window of the EOS Visit of their qualifying/index study (Exclusion 1-3): Blood dyscrasas, including: a. Hgb <10 g/dL or Hct <33%. b. WBC <3.0 x 109/L. c. Neutrophil count <1.2 x 109/L. d. Platelet count <100 x 109/L. e. Lymphocyte count of <0.75 x 109/L.
2. Estimated glomerular filtration rate [GFR] <40 mL/min/1.73 m2 calculated using Bedside Schwartz formula (Appendix 5) at the Screening Visit.
3. Aspartate aminotransferase (AST) or alanine inotransferase (ALT) ³1.5 times the upper limit of normal or any other clinically significant laboratory abnormality.
4. For all subjects: Persistent oligoarthritis, and undifferentiated JIA.
5. Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease.
6. History of any other rheumatic autoimmune disease, other than Sjogren's syndrome.
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) Chronic infections. b) Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 3 months prior to the first dose of study drug: c) Any treated infections within 2 weeks of baseline visit. (excluding those treated with topicals only) d) A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.e.History of infected joint prosthesis with prosthesis still in situ.
9. History of recurrent (more than one episode) herpes zoster or a single episode of disseminated herpes zoster or a single episode of disseminated (both oral and gential lesions simutaneously, or widespread lesions not contaminaed to oral or gential regions alone) herpes simplex.
10. Subjects taking potent and moderate cytochrome P450 3A4 (CYP3A4) inhibitors (Appendix 6).
11. Subjects taking potent and moderate CYP3A4 inducers (Appendix 6).
12. Participation in studies of investigational compounds (excluding qualifying/index study with tofacitinib) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug. Subjects 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]. 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.
14. Pregnant or nursing females are excluded.
15. Intramuscular or intravenous corticosteroids in the 4 weeks preceding first dose of study medication (oral cortico steroids permitted as per inclusion criterion).
16. Subjects 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 for further information regarding avoidance of household contacts who may be vaccinated).
17. Use of prohibited 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 4 weeks prior to the first dose of study medication.
19. Subjects with a first degree relative with a hereditary immunodeficiency; IgA deficiency not exclusionary.
20. Subjects 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. See Protocol Section 4.2 for additional exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Standard laboratory safety data and adverse event (AE) reports. Body weight, height and Tanner Stages will be collected to assess growth and physical development.

Secondary endpoints 15

1. Physician global evaluation of disease activity at each visit.
2. Number of joints with active arthritis at each visit.
3. Number of joints with limitation of motion at each visit.
4. Index of inflammation (C reactive protein [CRP]) and Erythrocyte Sedimentation Rate [ESR]) at each visit.
5. Childhood Health Assessment Questionnaire (CHAQ) at each visit.
6. Parent's Assessment of Physical Function (CHAQ Disability Index).
7. Parent's Assessment of Child's Arthritis Pain (CHAQ Discomfort Index, Visual Analog Scale [VAS]).
8. Parent's Assessment of Overall Wellbeing (CHAQ subsection Visual Analog Scale [VAS]).
9. JIA American College of Rheumatology (ACR) response and occurrence of JIA ACR disease flare at each visit.
10. JIA American Clinical Inactive Disease status and Clinical Remission of Medication at each visit and occurrence of JIA ACR disease flare at each visit after Month 3.
11. Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27-CRP and JADAS 27-ESR, and occurrence of JADAS minimum disease activity and inactive disease at each visit.
12. Eligibility of tapering defined per protocol for corticosteroids, MTX/lefluomide, and tofacitinib.
13. In subjects with sJIA: "Absence of Fever", defined as absence of fever due to sJIA in the week preceding the assessment at each visit.
14. In subjects with Enthesitis Related Arthritis (ERA): Change from baseline in the Tender Entheseal Assessment, Modified Schober's Test, Overall Back Pain and Nocturnal Back Pain response at various visits.
15. In subjects with psoriatic arthritis (PsA): Change from baseline in body surface area (BSA) affected by psoriasis and Physician's Global Assessment (PGA) of psoriasis) at various visits.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 4

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications