Long-Term Safety Study Of Tofacitinib In Patients With Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis Clinical Trial

Official title:

A LONG-TERM, OPEN-LABEL FOLLOW-UP STUDY OF TOFACITINIB FOR TREATMENT OF JUVENILE IDIOPATHIC ARTHRITIS (JIA)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01500551
• Other study ID #: A3921145
• Secondary ID: 2011-004915-22JI
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: March 18, 2013
• Est. completion date: March 22, 2025

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate long-term safety and tolerability of tofacitinib in patients with JIA, who have previously participated in tofacitinib JIA studies.

Description:

This is a Phase 2/3, long term, open-label, follow-up study. Subjects will have previously participated in qualifying/index JIA studies of tofacitinib. Those who have already completed such participation and enroll outside the 14 day window following completion of the End of Study (EOS) Visit of the qualifying/index study will participate in a screening Visit to determine eligibility. A Baseline Visit will then occur within 28 days after the Screening Visit. For subjects who are completing participation in a qualifying study of tofacitinib and enrolling on the same day of the EOS Visit of the qualifying/index study, the EOS Visit of the qualifying/index study can be combined with the Screening and Baseline Visits for this study. The subjects who enroll within the 14 day window following completion of the EOS Visit of the qualifying/index study will participate in a combined Screening and Baseline Visit for this study. After the Baseline Visit, visits will occur at 1 month (1 month=30 days) and 3 months, then every 3 months thereafter as long as the subject remains in the study.

Approximately 340 participants are projected to enroll into this open label extension study after completing a qualifying/index study in the JIA program.

For subjects who entered this study from the A3921103 and A3921104 qualifying/index studies, their participation in this study ends after the first marketing approval of tofacitinib for the treatment of polyarticular course Juvenile Idiopathic Arthritis (pJIA) in any country. This study will end once the last subject, and all other subjects, who entered from index study A3921165 have completed approximately 1 year in this study, or after the first marketing approval of tofacitinib for the treatment of systemic JIA, whichever comes first.

The total duration of an individual subject's participation may vary depending upon when they enter the trial.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 275
• Est. completion date: March 22, 2025
• Est. primary completion date: March 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• Pediatric subjects 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 JIA disease activity to warrant use of tofacitinib as a DMARD. Subjects turning 18 years of age during participation in the qualifying/index study or subsequently will be eligible for participation in this study.

• The subject has discontinued disallowed concomitant medications for the required time prior to the first dose of study drug, as defined in Appendix 1, and is taking only those concomitant medications in doses and frequency allowed by the protocol.

• Fertile male subjects 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 as outlined in this protocol throughout the study and for at least 28 days after the last dose of study medication.

• Subjects must have previously completed participation in a qualifying study of tofacitinib for the treatment of JIA. Subjects who have required earlier discontinuation of treatment in a qualifying study for reasons other than tofacitinib related serious adverse events may be eligible.

Exclusion Criteria:

• persistent oligoarthritis, and undifferentiated JIA.

• Infections:

1. Chronic infections.

2. 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.

3. Any treated infections within 2 weeks of baseline visit.

4. A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.

5. History of infected joint prosthesis with prosthesis still in situ.

• History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Tofacitinib
Tofacitinib will be administered orally BID (twice daily) approximately 12 hours (±2 hours) apart, once in the morning and once in the evening, based on body weight for all subjects for all three index studies (A3921103, A3921104, and A3921165) 5 mg BID Dose Level: Body Weight (Dose in tablet [mg BID] or solution [ml BID]) 5 - < 7 kg (2 mg or 2 ml) 7 - < 10 kg (2.5 mg or 2.5 ml) 10 - <15 kg (3 mg or 3 ml) 15 - <25 kg (3.5 mg or 3.5 ml) 25 - <40 kg (4 mg or 4 ml) >=40 kg (5 mg or 5 ml) Oral solution (1 mg/mL concentration) will be used for subjects weighing <40 kg. Oral tablets (5 mg) will be used for subjects weighing >=40 kg; subjects who are unable to swallow tablets will have the option of taking oral solution. Subjects will swallow study tablets whole and will not manipulate or chew tablets prior to swallowing.
• Tofacitinib
For subjects rolling over from study A3921103 and actively participating in this study at the time of Protocol Amendment 6 and receiving a dosage of tofacitinib in accordance with the dosing scheme specified in Protocol Amendment 5, investigators will have the option of maintaining the subject's current dosage regimen from index study A3921103 (if the desired clinical response has been attained with no safety concern) or adjusting the dosage regimen in accordance with the dosing scheme specified in this section.

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Instituto CAICI SRL	Rosario	Santa FE
Argentina	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman
Australia	The Royal Children's Hospital	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Belgium	Queen Fabiola Children's University Hospital	Brussels
Belgium	UZ Gent	Gent
Belgium	UZ Leuven - Gasthuisberg	Leuven
Brazil	Faculdade de Medicina da UNESP	Botucatu	SAO Paulo
Brazil	Hospital de Clinicas da UNICAMP	Campinas	SAO Paulo
Brazil	Hospital de Clinicas da UNICAMP-Laboratorio de Reumatologia-L06	Campinas	SAO Paulo
Brazil	Hospital Pequeno Príncipe Clinical Research Office	Curitiba	Parana
Brazil	Hospital Pequeno Príncipe/	Curitiba	Parana
Brazil	CMIP - Centro Mineiro de Pesquisa Ltda	Juiz de Fora	Minas Gerais
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	Instituto de Puericultura e Pediatria Martagao Gesteira (IPPMG)	Rio de Janeiro
Brazil	SER - Serviços Especializados em Reumatologia	Salvador	Bahia
Brazil	Instituto da Crianca do Hospital das Clinicas da FMUSP	Sao Paulo
Brazil	SPDM - Associacao Paulista para o Desenvolvimento da Medicina	Sao Paulo
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	McGill University Health Center, Glen Site	Montreal	Quebec
Canada	McGill University Health Center, Glen Site, Central Pharmacy	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	C & W Health Centre of BC	Vancouver	British Columbia
Canada	Teck Acute Care Centre	Vancouver	British Columbia
China	Beijing Children's Hospital, Capital Medical University/Rheumatology Department	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Chengdu Women's and Children's Central Hospital	Chengdu	Sichuan
China	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Guangzhou Women and Children's Medical Center	Guangzhou	Guangdong
China	The Children's Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Children's Hospital of Fudan University	Shanghai
China	Children's Hospital of Soochow University	Suzhou	Jiangsu
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei
China	Xi'an Children's Hospital	Xi'an	Shaanxi
Costa Rica	Hospital Metropolitano	San Jose
Germany	PRI - Pediatric Rheumatology Research Institute GmbH	Bad Bramstedt
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	Universitaets-Kinderklinik Charite SPZ Kinderrheumatologie	Berlin
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Klinikum Bremen-Mitte, Prof. Hess-Kinderklinik	Bremen
Germany	Universitaetsklinikum Carl Gustav Carus Dresden Klinik und Poliklinik fur Kinder-und Jugendmedizin	Dresden
Germany	Universitaetsklinikum Erlangen Kinder- und Jugendklinik	Erlangen	Bayern
Germany	Deutsches Zentrum für Kinder- und Jugendrheumatologie	Garmisch-partenkirchen
Germany	Hamburger Zentrum fur Kinder und Jugendrheumatologie	Hamburg
Germany	Asklepios Klinik Sankt Augustin GmbH	Sankt Augustin
Germany	St. Josef-Stift Sendenhorst	Sendenhorst
Hungary	Semmelweis Egyetem	Budapest
India	Institute of Child Health	Kolkata	WEST Bengal
India	Institute of Post Graduate Medical Education and Research & SSKM Hospital	Kolkata	WEST Bengal
India	Sir Ganga Ram Hospital	New Delhi
India	Nirmal Hospital Pvt Ltd.	Surat	Gujarat
Israel	Rambam Health Care	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Meir Medical Center - Pediatric Clinic	Kfar Saba
Israel	Chaim Sheba M.C Tel hashomer	Ramat Gan
Italy	IRCCS Giannina Gaslini Department/Division	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano	Milan
Mexico	Clínica de Investigacion en Reumatologia y Obesidad, S.C.	Guadalajara	Jalisco
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Mexico	Centro de Alta Especialidad de Reumatología e Investigación del Potosí, S.C.	San Luis De Potosí
Mexico	Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosi
Mexico	Unidad de Investigaciones Reumatologicas A.C.	San Luis Potosi
Poland	Wojewodzki Szpital Dzieciecy im. J. Brudzinskiego	Bydgoszcz
Poland	Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie	Krakow
Poland	Klinika Kardiologii i Reumatologii Dzieciecej	Lodz
Poland	Centrum Pediatrii im. Jana Pawla II w Sosnowcu Sp. z o.o.	Sosnowiec
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im prof dr hab med Eleonory Reicher	Warszawa
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa
Russian Federation	Federal State Budgetary Scientific Institution	Moscow
Russian Federation	FSAEI HE I.M. Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University)	Moscow
Russian Federation	FSAEI HE I.M. Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University),	Moscow
Russian Federation	FSAI "NMRCCH" of MOH Russia	Moscow
Russian Federation	FSBEI HE "St. Petersburg State Pediatric Medical University" of the Ministry of Healthcare	Saint-Petersburg
Russian Federation	State Budgetary Healthcare Institution of Samara Region "Tolyatti City Clinical Hospital #5"	Tolyatti
Russian Federation	Clinic of FSBEI HE BSMU MoH RF	Ufa	Republic OF Bashkortostan
Russian Federation	FSBEI HE BSMU MoH RF	Ufa	Republic OF Bashkortostan
Slovakia	Narodny ustav detskych chorob, Detska klinika LF UK a NUDCH	Bratislava
Slovakia	Detska Fakultna nemocnica Kosice	Kosice
Slovakia	Narodny ustav reumatickych chorob	Piestany
South Africa	Durban International Clinical Research Site, Enhancing Care Foundation	Durban
South Africa	Enhancing Care Foundation	Durban	Kwazulu-natal
South Africa	Panorama Medical Centre	Panorama	Cape Town
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Umraniye Training and Research Hospital	Istanbul
Turkey	Umraniye Training and Research Hospital	Istanbul
Turkey	Istanbul Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi Cocuk Romatoloji Bolumu	Kadikoy / Istanbul
Turkey	Erciyes University Medical Faculty	Kayseri
Ukraine	Communal Institution "Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child n.a.	Dnipro
Ukraine	Ivano-Frankivsk Regional Children's Clinical Hospital	Ivano-Frankivsk
Ukraine	Communal Non-profit Enterprise	Vinnytsia
United Kingdom	Birmingham Woman's and Children's NHS Foundation Trust	Birmingham	WEST Midlands
United Kingdom	NHS Greater Glasgow and Clyde Royal Hospital for Children	Glasgow
United States	Center for Advanced Pediatrics	Atlanta	Georgia
United States	AU Medical Center	Augusta	Georgia
United States	Augusta University	Augusta	Georgia
United States	Augusta University Health Pharmacy	Augusta	Georgia
United States	Dell Children's Medical Group, Dell Children's Medical Center	Austin	Texas
United States	Tufts Medical Center - Floating Hospital for Children	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	UNC Children's Hospital	Chapel Hill	North Carolina
United States	UNC Clinical & Translational Research Unit	Chapel Hill	North Carolina
United States	Atrium Health- Investigational Drug Services	Charlotte	North Carolina
United States	Levine Children's Specialty Center	Charlotte	North Carolina
United States	Pediatric Research	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Lurie Rheumatology Offices	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Texas Children's Hospital- Clinical Care Center	Houston	Texas
United States	Texas Children's Hospital- Clinical Research Center	Houston	Texas
United States	Texas Children's Hospital- Investigational Pharmacy	Houston	Texas
United States	Texas Children's Hospital- Main Hospital	Houston	Texas
United States	Texas Children's Hospital/Baylor College of Medicine- Feigin Center	Houston	Texas
United States	Riley Hospital for Children at IU Health	Indianapolis	Indiana
United States	Cohen Children's Medical Center of New York	Lake Success	New York
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Loma Linda University Children'S Hospital	Loma Linda	California
United States	Loma Linda University Clinical Trials Center	Loma Linda	California
United States	Loma Linda University Eye Institute	Loma Linda	California
United States	Loma Linda University General Pediatric Clinic - Meridian	Loma Linda	California
United States	Pediatric Speciality Team Centers of LLU Children's Hospital (Rheumatology)	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Explorer Clinic, University of Minnesota Children's Hospital	Minneapolis	Minnesota
United States	Columbia University Medical Center-Herbert Irving Pavillion	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	AdventHealth	Orlando	Florida
United States	AdventHealth Investigational Drug Services	Orlando	Florida
United States	AdventHealth Pediatric Outpatient Procedures and Sedation	Orlando	Florida
United States	AHMG Pediatric Rheumatology and Immunology	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Phoenix Children's Hospital- Inpatient Pharmacy	Phoenix	Arizona
United States	Randall Children's Hospital at Legacy Emanuel	Portland	Oregon
United States	UNC Children's Raleigh	Raleigh	North Carolina
United States	Johns Hopkins All Children's Hospital	Saint Pertersburg	Florida
United States	All Children's Hospital Speciality Physicians	Saint Petersburg	Florida
United States	Intermountain - Primary Children's Hospital	Salt Lake City	Utah
United States	Pediatric Speciality Team Centers of LLU Children's Hospital (Rheumatology)	San Bernardino	California
United States	Rady Children's Hospital Center for Pediatric Clinical Research	San Diego	California
United States	Rady Children's Hospital Education and Office Building	San Diego	California
United States	Rady Children's Hospital Research Pharmacy	San Diego	California
United States	Rady Children's Hospital Rheumatology Clinic	San Diego	California
United States	Rady Children's Hospital San Diego	San Diego	California
United States	Rady Children's Hospital San Diego- Education and Office Building	San Diego	California
United States	Rady Children's Research Pharmacy	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia
United States	IDS Pharmacy	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Costa Rica,  Germany,  Hungary,  India,  Israel,  Italy,  Mexico,  Poland,  Russian Federation,  Slovakia,  South Africa,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Standard laboratory safety data and adverse event (AE) reports. Body weight, height and Tanner Stages will collected to assess growth and physical development.		up to 8 years
Secondary	Physician global evaluation of disease activity at each visit.		up to 8 years
Secondary	Number of joints with active arthritis at each visit.		up to 8 years
Secondary	Number of joints with limitation of motion at each visit.		up to 8 years
Secondary	Index of inflammation (C-reactive protein [CRP] and Erythrocyte Sedimentation Rate [ESR]) at each visit.		up to 8 years
Secondary	Parent's Assessment of Physical Function (Childhood Health Assessment Questionnaire [CHAQ]Disability Index)at each visit.		up to 8 years
Secondary	Parent's Assessment of Child's Arthritis Pain (Childhood Health Assessment Questionnaire [CHAQ] Discomfort Index, Visual Analog Scale [VAS])at each visit.		up to 8 years
Secondary	Parent's Global Assessment of Overall Wellbeing (Childhood Health Assessment Questionnaire [CHAQ] subsection, Visual Analog Scale [VAS])at each visit.		up to 8 years
Secondary	JIA American College of Rheumatology (ACR) response and occurrence of JIA ACR disease flare at each visit.		up to 8 years
Secondary	JIA ACR Clinical Inactive Disease status and Clinical Remission on Medication at each visit.		up to 8 years
Secondary	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.		up to 8 years
Secondary	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 responses at various visits.		up to 8 years
Secondary	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.		up to 8 years
Secondary	In subjects with sJIA: "Absence of Fever", defined as absence of fever due to sJIA in the week preceding the assessment at each visit.		up to 8 years
Secondary	Eligibility of tapering defined per protocol for corticosteroids		up to 8 years
Secondary	Eligibility of tapering defined per protocol for methotrexate		up to 8 years
Secondary	Eligibility of tapering defined per protocol for leflunomide		Up to 8 years
Secondary	Eligibility of tapering defined per protocol for tofacitinib		Up to 8 years

External Links

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