A Safety, Efficacy And Pharmacokinetics Study Of Tofacitinib In Pediatric Patients With sJIA

Phase 3

Completed

• Conditions: Arthritis Juvenile Idiopathic

• Registration Number: NCT03000439
• Lead Sponsor: Pfizer

Brief Summary

A randomized withdrawal study in which responders to open-label treatment with tofacitinib will be randomized in a 1:1 ratio to tofacitinib or placebo in a double-blind phase. In the double-blind phase "time to sJIA flare" will be evaluated as primary endpoint and subjects will be discontinued once they experience sJIA flare. An interim analysis for efficacy and futility will be conducted when at least 20 flares have been observed. If either criterion is met, the study will be stopped. If neither criterion is met, the study will continue until the requisite number of flares are observed as determined by the number of flares included in the interim analysis and a statistical penalty for conducting the interim analysis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-09
• Study First Submitted QC: 2016-12-19
• Study First Posted: 2016-12-22
• Study Start: 2018-05-10
• Primary Completion: 2024-03-27
• Study Completion: 2024-03-27
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• active sJIA disease according to ILAR criteria before screening and at baseline (Day 1);
• Treatment with stable doses of methotrexate (MTX) ≤25 mg/week or ≤20 mg/m2/week, whichever is lower, is permitted;
• Treatment with a stable dose of oral prednisone ≤1 mg/kg/day up to a maximum of 30 mg/day, or equivalent, for at least 1 week before the first study drug dose is permitted.

Exclusion Criteria

• Previous juvenile idiopathic arthritis (JIA) treatment with tofacitinib.
• Current symptoms or findings of myocarditis, endocarditis or more than minimal pericardial effusion associated with systemic juvenile idiopathic arthritis (sJIA). Current symptoms or findings of more than minimal pleuritis with sJIA.
• Current infection or serious infection within 3 months of study enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Time to flare	Up to 82 weeks after randomization	Time to sJIA disease flare in the double-blind phase

Secondary Outcome Measures

Name	Time	Method
Time to first Adapted JIA ACR 30 response in Part 1 of the open label phase.	12 to 40 weeks
Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS 27) at every visit from Day 7 onward in the open label and double blind phase.	Up to 82 weeks after randomization.
Occurrence of disease flare in double-blind phase	Up to 82 weeks after randomization	disease flare frequency by visit in the double-blind phase.
Achievement of corticosteroid tapering at the end of the open-label phase	12 to 40 weeks	Rate of successful corticosteroid tapering.
Achievement of a corticosteroid dose of 0.2 mg/kg/day or 10 mg/day (whichever is lower) at the end of the open label treatment period	12 to 40 weeks
Adapted sJIA ACR 30/50/70/90/100 response at every visit from Day 7 onward in the open label and double blind phase.	Up to 82 weeks after randomization
Fever (Temp >38 Degrees Celsius) attributed to sJIA at Day 3, Day 7 and Day 14 of the open label phase.	Day 3, Day 7, Day 14
CRP ≤ 10 mg/L at every visit of the open label phase.	12 to 40 weeks
"Absence of fever", defined as absence of fever due to sJIA in the week preceding the assessment at every visit from Day 7 onward in the open label and double blind phase.	Up to 82 weeks after randomization.
Change from baseline in each JIA ACR core variable at every visit from Day 7 onward in the open label and double blind phase.	Up to 82 weeks after randomization.
Change from baseline in Child Health Questionnaire (CHQ) responses at the end of Part 1 and Part 2 of the open label phase, at randomization and every 3 months thereafter.	Up to 82 weeks after randomization.
Change from baseline in Child Health Assessment Questionnaire (CHAQ) at every visit from Day 7 onward in the open label and double blind phase.	Up to 82 weeks after randomization.
Occurrence of inactive disease status and minimal disease activity clinical remission at every visit from Day 7 onward (JADAS 27) in the open label and double blind phase.	Up to 82 weeks after randomization.
Occurrence of inactive disease status and clinical remission at every visit from Day 7 onward (JIA ACR) in the open label and double blind phase.	Up to 82 weeks after randomization.

Trial Locations

Locations (96)

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

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 Fudan University; 🇨🇳 Shanghai, China

The Children's Hospital Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Enhancing Care Foundation; 🇿🇦 Durban, Kwazulu-natal, South Africa

Instituto CAICI SRL; 🇦🇷 Rosario, Santa FE, Argentina

Institute of Child Health; 🇮🇳 Kolkata, WEST Bengal, India

AdventHealth Pediatric Outpatient Procedures and Sedation; 🇺🇸 Orlando, Florida, United States

AdventHealth; 🇺🇸 Orlando, Florida, United States

AHMG Pediatric Rheumatology and Immunology; 🇺🇸 Orlando, Florida, United States

AU Medical Center; 🇺🇸 Augusta, Georgia, United States

Cohen Children's Medical Center of New York; 🇺🇸 New Hyde Park, New York, United States

UNC Children's Hospital; 🇺🇸 Chapel Hill, North Carolina, United States

Cincinnati Children's Hospital Medical Center Investigational Drug Service; 🇺🇸 Cincinnati, Ohio, United States

Randall Children's Hospital at Legacy Emanuel; 🇺🇸 Portland, Oregon, United States

UPECLIN Unidade de Pesquisa Clinica da Faculdade de Medicina da UNESP; 🇧🇷 Botucatu, SAO Paulo, Brazil

SPDM - Associacao Paulista para o Desenvolvimento da Medicina; 🇧🇷 Sao Paulo, Brazil

Instituto da Crianca do Hospital das Clinicas da FMUSP; 🇧🇷 Sao Paulo, Brazil

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Research Institute of McGill University Health Center, Glen site; 🇨🇦 Montreal, Quebec, Canada

CHU de Québec - Université Laval, Site CHUL; 🇨🇦 Quebec City, Quebec, Canada

Children's Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

Guangzhou Women and Children's Medical Center; 🇨🇳 Guangzhou, Guangdong, China

Children's Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Xi'an Children's Hospital; 🇨🇳 Xi'an, Shaanxi, China

Beijing Children's Hospital, Capital Medical University/Rheumatology Department; 🇨🇳 Beijing, China

HELIOS Kliniken Berlin Buch GmbH; 🇩🇪 Berlin, Germany

Universitaetsklinikum Erlangen; 🇩🇪 Erlangen, Bayern, Germany

Deutsches Zentrum für Kinder- und Jugendrheumatologie; 🇩🇪 Garmisch-partenkirchen, Germany

Universitaetsklinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

Charite - Universitaetsmedizin Berlin, Campus Virchow; 🇩🇪 Berlin, Germany

Nirmal Hospital Pvt Ltd; 🇮🇳 Surat, Gujarat, India

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Meir Medical Center- Pharmacy; 🇮🇱 Kfar Saba, Israel

Istituto Giannina Gaslini Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico; 🇮🇹 Genova, Genoa, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Milan, Italy

Clínica de Investigacion en Reumatologia y Obesidad, S.C.; 🇲🇽 Guadalajara, Jalisco, Mexico

SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi; 🇵🇱 Lodz, Poland

WIP Warsaw IBD Point Profesor Kierkus; 🇵🇱 Warsaw, Poland

Clinic of FSBEI HE BSMU MoH RF; 🇷🇺 Ufa, Republic OF Bashkortostan, Russian Federation

Detska Fakultna nemocnica Kosice; 🇸🇰 Kosice, Slovakia

Federal State Budgetary Scientific Institution "Scientific and Research Rheumatology; 🇷🇺 Moscow, Russian Federation

Panorama Medical Centre; 🇿🇦 Cape Town, Western CAPE, South Africa

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario y Politecnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Istanbul University Cerrahpasa - Cerrahpasa Tip Fakultesi Clinical Research Center; 🇹🇷 Fatih / Istanbul, Turkey

Umraniye Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Istanbul Goztepe Prof. Dr. Suleyman Yalcin City Hospital Department of Pediatric Rheumatology; 🇹🇷 Kadikoy / Istanbul, Turkey

Erciyes Universitesi Tip Fakultesi Hastanesi; 🇹🇷 Kayseri, Turkey

CNE of Lviv Regional Council "Western Ukrainian Specialized Pediatric; 🇺🇦 Lviv, Ukraine

Communal Institution "Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child n.a.; 🇺🇦 Dnipro, Ukraine

Vinnytsia Regional Children's Clinical Hospital; 🇺🇦 Vinnytsia, Ukraine

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

All Children's Hospital Specialty Physicians; 🇺🇸 Saint Petersburg, Florida, United States

Lurie Rheumatology Offices; 🇺🇸 Chicago, Illinois, United States

St. Josef-Stift Sendenhorst; 🇩🇪 Sendenhorst, Germany

Meir Medical Center - Pediatric Clinic; 🇮🇱 Kfar Saba, Israel

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Ann & Robert H Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

UNC Children's Raleigh; 🇺🇸 Raleigh, North Carolina, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

PPD Sample Management Department (PK Laboratory); 🇺🇸 Middleton, Wisconsin, United States

Centro Medico Privado de Reumatologia; 🇦🇷 San Miguel de Tucuman, Tucuman, Argentina

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Hopital Universitaire des Enfants Reine Fabiola (HUDERF); 🇧🇪 Brussels, Belgium

Hospital de Clinicas da UNICAMP; 🇧🇷 Campinas, SAO Paulo, Brazil

McGill University Health Center, Glen Site; 🇨🇦 Montreal, Quebec, Canada

Faculdade de Medicina da UNESP; 🇧🇷 Botucatu, SÃO Paulo, Brazil

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology; 🇨🇳 Wuhan, Hubei, China

HELIOS Klinikum Berlin Buch GmbH; 🇩🇪 Berlin, Germany

Gesundheit Nord gGmbH; 🇩🇪 Bremen, Germany

Sir Ganga Ram Hospital; 🇮🇳 Rajinder Nagar, NEW Delhi, India

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Asklepios Klinik Sankt Augustin GmbH, Zentrum für Allgemeine Pädiatrie und Neonatologie; 🇩🇪 Sankt Augustin, Germany

Narodny ustav reumatickych chorob; 🇸🇰 Piestany, Slovakia

Emmed Research; 🇿🇦 Pretoria, Gauteng, South Africa

Hacettepe University Medical Faculty; 🇹🇷 Ankara, Turkey

Municipal non-Profit Enterprise; 🇺🇦 Ivano-Frankivsk, Ukraine

NHS Greater Glasgow and Clyde, Royal Hospital for Children; 🇬🇧 Glasgow, United Kingdom

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UNC Clinical & Translational Research Center; 🇺🇸 Chapel Hill, North Carolina, United States

Alberta Children's Hospital/University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Hospital Metropolitano; 🇨🇷 San Jose, Costa Rica

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

Institute of Post Graduate Medical Education and Research & SSKM Hospital; 🇮🇳 Kolkata, WEST Bengal, India

Augusta University; 🇺🇸 Augusta, Georgia, United States

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"; 🇲🇽 Monterrey, Nuevo LEON, Mexico

Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.; 🇲🇽 San Luis Potosi, Mexico

Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie; 🇵🇱 Krakow, Poland

Narodny ustav detskych chorob, Detska klinika LF UK a NUDCH; 🇸🇰 Bratislava, Slovakia

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States