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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT01500551

Collaborator

(none)

340

Enrollment

138

Locations

Arm

143.8

Anticipated Duration (Months)

2.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Tofacitinib Drug: Tofacitinib	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 18, 2013

Anticipated Primary Completion Date :

Mar 11, 2025

Anticipated Study Completion Date :

Mar 11, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tofacitinib All patients will be in tofacitinib treatment group.	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. Other Names: CP 690,550, Xeljanz Drug: 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. Other Names: CP-690,550, Xeljanz

Arm

Intervention/Treatment

Experimental: Tofacitinib

All patients will be in tofacitinib treatment group.

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.

Other Names:

CP 690,550, Xeljanz

Drug: 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.

Other Names:

CP-690,550, Xeljanz

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Physician global evaluation of disease activity at each visit. [up to 8 years]
Number of joints with active arthritis at each visit. [up to 8 years]
Number of joints with limitation of motion at each visit. [up to 8 years]
Index of inflammation (C-reactive protein [CRP] and Erythrocyte Sedimentation Rate [ESR]) at each visit. [up to 8 years]
Parent's Assessment of Physical Function (Childhood Health Assessment Questionnaire [CHAQ]Disability Index)at each visit. [up to 8 years]
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]
Parent's Global Assessment of Overall Wellbeing (Childhood Health Assessment Questionnaire [CHAQ] subsection, Visual Analog Scale [VAS])at each visit. [up to 8 years]
JIA American College of Rheumatology (ACR) response and occurrence of JIA ACR disease flare at each visit. [up to 8 years]
JIA ACR Clinical Inactive Disease status and Clinical Remission on Medication at each visit. [up to 8 years]
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]
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]
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]
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]
Eligibility of tapering defined per protocol for corticosteroids [up to 8 years]
Eligibility of tapering defined per protocol for methotrexate [up to 8 years]
Eligibility of tapering defined per protocol for leflunomide [Up to 8 years]
Eligibility of tapering defined per protocol for tofacitinib [Up to 8 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Chronic infections.
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.
Any treated infections within 2 weeks of baseline visit.
A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital- Inpatient Pharmacy	Phoenix	Arizona	United States	85016
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
4	Loma Linda University Children'S Hospital	Loma Linda	California	United States	92354
5	Loma Linda University Clinical Trials Center	Loma Linda	California	United States	92354
6	Loma Linda University Eye Institute	Loma Linda	California	United States	92354
7	Loma Linda University General Pediatric Clinic - Meridian	Loma Linda	California	United States	92354
8	Pediatric Speciality Team Centers of LLU Children's Hospital (Rheumatology)	Loma Linda	California	United States	92408
9	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
10	Pediatric Speciality Team Centers of LLU Children's Hospital (Rheumatology)	San Bernardino	California	United States	92408
11	Rady Children's Hospital Center for Pediatric Clinical Research	San Diego	California	United States	92123
12	Rady Children's Hospital Education and Office Building	San Diego	California	United States	92123
13	Rady Children's Hospital Research Pharmacy	San Diego	California	United States	92123
14	Rady Children's Hospital Rheumatology Clinic	San Diego	California	United States	92123
15	Rady Children's Hospital San Diego	San Diego	California	United States	92123
16	Connecticut Children's Medical Center Pharmacy	Hartford	Connecticut	United States	06106
17	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
18	Children's National Medical Center	Washington	District of Columbia	United States	20010
19	IDS Pharmacy	Washington	District of Columbia	United States	20010
20	Nicklaus Children's Hospital	Miami	Florida	United States	33155
21	Johns Hopkins All Children's Hospital	Saint Pertersburg	Florida	United States	33701
22	All Children's Hospital Speciality Physicians	Saint Petersburg	Florida	United States	33701
23	Center for Advanced Pediatrics	Atlanta	Georgia	United States	30329
24	Augusta University Health Pharmacy	Augusta	Georgia	United States	30912
25	Augusta University	Augusta	Georgia	United States	30912
26	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
27	Lurie Children's Investigational Drug Pharmacy	Chicago	Illinois	United States	60611
28	Lurie Rheumatology Offices	Chicago	Illinois	United States	60611
29	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
30	IU Health Investigational Drug Services	Indianapolis	Indiana	United States	46202
31	Riley Hospital for Children at IU Health	Indianapolis	Indiana	United States	46202
32	Tufts Medical Center - Floating Hospital for Children	Boston	Massachusetts	United States	02111
33	Explorer Clinic, University of Minnesota Children's Hospital	Minneapolis	Minnesota	United States	55454
34	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
35	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
36	Montefiore Medical Center	Bronx	New York	United States	10467
37	Cohen Children's Medical Center of New York	Lake Success	New York	United States	11042
38	Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
39	Columbia University Medical Center-Herbert Irving Pavillion	New York	New York	United States	10031
40	Pediatric Research	Charlotte	North Carolina	United States	20207
41	Levine Children's Specialty Center	Charlotte	North Carolina	United States	28203
42	Atrium Health- Investigational Drug Services	Charlotte	North Carolina	United States	28207
43	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
44	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
45	Legacy Emanuel Medical Center - Inpatient Pharmacy	Portland	Oregon	United States	97227
46	Randall Children's Hospital at Legacy Emanuel	Portland	Oregon	United States	97227
47	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
48	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
49	Dell Children's Medical Group, Dell Children's Medical Center	Austin	Texas	United States	78723
50	Texas Children's Hospital- Clinical Care Center	Houston	Texas	United States	77030
51	Texas Children's Hospital- Clinical Research Center	Houston	Texas	United States	77030
52	Texas Children's Hospital- Investigational Pharmacy	Houston	Texas	United States	77030
53	Texas Children's Hospital- Main Hospital	Houston	Texas	United States	77030
54	Texas Children's Hospital/Baylor College of Medicine- Feigin Center	Houston	Texas	United States	77030
55	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
56	Seattle Children's Hospital	Seattle	Washington	United States	98105
57	Instituto CAICI SRL	Rosario	Santa FE	Argentina	S2000PBJ
58	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman	Argentina	T4000AXL
59	Hospital Britanico de Buenos Aires	Caba		Argentina	C1280AEB
60	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
61	The Royal Children's Hospital	Parkville	Victoria	Australia	3052
62	UZ Gent	Gent		Belgium	9000
63	UZ Leuven - Gasthuisberg	Leuven		Belgium	3000
64	SER - Serviços Especializados em Reumatologia	Salvador	Bahia	Brazil	40150-150
65	CMIP - Centro Mineiro de Pesquisa Ltda	Juiz de Fora	Minas Gerais	Brazil	36010-570
66	Hospital Pequeno Príncipe/	Curitiba	Parana	Brazil	80250-060
67	Hospital de Clínicas de Porto Alegre	Porto Alegre	RIO Grande DO SUL	Brazil	90035-903
68	Faculdade de Medicina da UNESP	Botucatu	SAO Paulo	Brazil	18618-686
69	Hospital de Clinicas da UNICAMP-Laboratorio de Reumatologia-L06	Campinas	SAO Paulo	Brazil	13083-881
70	Hospital de Clinicas da UNICAMP	Campinas	SAO Paulo	Brazil	13083-888
71	Instituto de Puericultura e Pediatria Martagao Gesteira (IPPMG)	Rio de Janeiro		Brazil	21941-912
72	SPDM - Associacao Paulista para o Desenvolvimento da Medicina	Sao Paulo		Brazil	04037-002
73	Instituto da Crianca do Hospital das Clinicas da FMUSP	Sao Paulo		Brazil	05409-011
74	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
75	Teck Acute Care Centre	Vancouver	British Columbia	Canada	V5Z2H6
76	C & W Health Centre of BC	Vancouver	British Columbia	Canada	V6H 3N1
77	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
78	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
79	McGill University Health Center, Glen Site, Central Pharmacy	Montreal	Quebec	Canada	H4A 3J1
80	McGill University Health Center, Glen Site	Montreal	Quebec	Canada	H4A 3J1
81	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing	China	401122
82	Children's Hospital of Soochow University	Suzhou	Jiangsu	China	215003
83	Xi'an Children's Hospital	Xi'an	Shaanxi	China	710003
84	Children's Hospital Affiliated to Capital Institute of Pediatrics/Rheumatology Immunology	Beijing		China	100020
85	Beijing Children's Hospital, Capital Medical University/Rheumatology Department	Beijing		China	100045
86	Children's Hospital of Fudan University	Shanghai		China	201102
87	Hospital Metropolitano	San Jose		Costa Rica	10103
88	PRI - Pediatric Rheumatology Research Institute GmbH	Bad Bramstedt		Germany	24576
89	Klinikum Bremen-Mitte, Prof. Hess-Kinderklinik	Bremen		Germany	28177
90	Deutsches Zentrum für Kinder- und Jugendrheumatologie	Garmisch-partenkirchen		Germany	82467
91	Hamburger Zentrum fur Kinder und Jugendrheumatologie	Hamburg		Germany	22081
92	Asklepios Klinik Sankt Augustin GmbH	Sankt Augustin		Germany	53757
93	St. Josef-Stift Sendenhorst	Sendenhorst		Germany	48324
94	Rambam Health Care Campus	Haifa		Israel	3109601
95	Meir Medical Center	Kfar Saba		Israel	4428164
96	Chaim Sheba M.C Tel hashomer	Ramat Gan		Israel	52621
97	Clínica de Investigacion en Reumatologia y Obesidad, S.C.	Guadalajara	Jalisco	Mexico	44650
98	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON	Mexico	64460
99	Centro de Alta Especialidad de Reumatología e Investigación del Potosí, S.C.	San Luis De Potosí		Mexico	78213
100	Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosi		Mexico	78290
101	Unidad de Investigaciones Reumatologicas A.C.	San Luis Potosi		Mexico	78290
102	Wojewodzki Szpital Dzieciecy im. J. Brudzinskiego	Bydgoszcz		Poland	85-667
103	Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie	Krakow		Poland	31-503
104	Klinika Kardiologii i Reumatologii Dzieciecej	Lodz		Poland	91-738
105	Centrum Pediatrii im. Jana Pawla II w Sosnowcu Sp. z o.o.	Sosnowiec		Poland	41-218
106	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im prof dr hab med Eleonory Reicher	Warszawa		Poland	02-637
107	FSBEI HE BSMU MoH RF	Ufa	Republic OF Bashkortostan	Russian Federation	450008
108	Clinic of FSBEI HE BSMU MoH RF	Ufa	Republic OF Bashkortostan	Russian Federation	450083
109	FSBEI HE "Kazan SMU" MoH RF	Kazan		Russian Federation	420138
110	SAHI CRCH MoH TR	Kazan		Russian Federation	420138
111	Federal State Budgetary Scientific Institution	Moscow		Russian Federation	115522
112	FSAEI HE I.M. Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University)	Moscow		Russian Federation	119435
113	FSAEI HE I.M. Sechenov First MSMU of Minzdrav of Russia (Sechenovskiy University),	Moscow		Russian Federation	119991
114	FSAI "NMRCCH" of MOH Russia	Moscow		Russian Federation	119991
115	FSBEI HE "St. Petersburg State Pediatric Medical University" of the Ministry of Healthcare	Saint-Petersburg		Russian Federation	194100
116	FSBEI HE Saratov SMU n.a. V.I.Razumovskiy MoH RF	Saratov		Russian Federation	410012
117	FSBEI HE Saratov SMU n.a. V.I.Razumovskiy MoH RF	Saratov		Russian Federation	410054
118	State Budgetary Healthcare Institution of Samara Region "Tolyatti City Clinical Hospital #5"	Tolyatti		Russian Federation	445039
119	State Budgetary Healthcare Institution of Sverdlovsk Region	Yekaterinburg		Russian Federation	620149
120	Narodny ustav detskych chorob, Detska klinika LF UK a NUDCH	Bratislava		Slovakia	83340
121	Detska Fakultna nemocnica Kosice	Kosice		Slovakia	04011
122	Narodny ustav reumatickych chorob	Piestany		Slovakia	921 12
123	Panorama Medical Centre	Panorama	Cape Town	South Africa	7500
124	Emmed Research	Pretoria	Gauteng	South Africa	0002
125	Enhancing Care Foundation	Durban	Kwa-zulu Natal	South Africa	4091
126	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
127	Hospital Universitario La Paz	Madrid		Spain	28046
128	Hospital Universitario y Politecnico La Fe	Valencia		Spain	46026
129	Hacettepe University Medical Faculty	Ankara		Turkey	06100
130	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
131	Umraniye Training and Research Hospital	Istanbul		Turkey	35767
132	Istanbul Goztepe Prof. Dr. Suleyman Yalcin City Hospital Department of Pediatric Rheumatology	Kadikoy / Istanbul		Turkey	34722
133	Erciyes University Medical Faculty	Kayseri		Turkey	38039
134	Communal Institution "Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child n.a.	Dnipro		Ukraine	49006
135	Municipal non-Profit Enterprise	Ivano-Frankivsk		Ukraine	76014
136	Communal Institution of Lviv Regional Council	Lviv		Ukraine	79035
137	Vinnytsia Regional Children's Clinical Hospital of Vinnytsia Regional Council	Vinnytsia		Ukraine	21000
138	Birmingham Woman's and Children's NHS Foundation Trust	Birmingham	WEST Midlands	United Kingdom	B4 6NH