Study of Oral Upadacitinib and Subcutaneous/Intravenous Tocilizumab to Evaluate Change in Disease Activity, Adverse Events and How Drug Moves Through the Body of Pediatric and Adolescent Participants With Active Systemic Juvenile Idiopathic Arthritis.
- Conditions
- Juvenile Idiopathic Arthritis
- Interventions
- Registration Number
- NCT05609630
- Lead Sponsor
- AbbVie
- Brief Summary
Juvenile Idiopathic Arthritis (JIA) is the most common type of arthritis that affects children. The term "idiopathic" means "of unknown origin". It is a chronic (long-lasting) disease that causes swelling, warmth, and pain of one or more small joints. Systemic JIA ia a rare and serious form of JIA. Systemic" means it may affect not only the joints but other parts of the body, including the liver, lungs and heart. sJIA is more severe and can be more challenging to diagnose and treat than other types of juvenile idiopathic arthritis. It is a lifelong disease for many patients and can continue into adulthood. This study will assess how safe and effective upadacitinib is in treating pediatric and adolescent participants aged 1 to \< 18 with systemic juvenile idiopathic arthritis (sJIA) and will include a tocilizumab treatment arm for reference. Adverse events and change in the disease activity will be assessed.
Upadacitinib is an investigational drug being developed for the treatment of sJIA. Participants are assigned to 1 of 2 cohorts. In cohort 1, participants will receive upadacitinib or tocilizumab reference. In cohort 2, participants will receive upadacitinib. Approximately 90 participants with sJIA will be enrolled in approximately 45 sites worldwide.
Participants will receive upadacitinib oral tablets once daily or oral solution twice daily or tocilizumab subcutaneous injection or intravenous infusion as per local label for 52 weeks and followed for approximately 30 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits/calls during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Baseline with a total body weight of 10 kg or higher at screening and symptoms of systemic juvenile idiopathic arthritis (sJIA) according to International League of Associations for Rheumatology (ILAR) criteria for at least 6 weeks prior to Screening, with onset prior to 16 years old, and meet the following conditions:
- Must have active sJIA with at least 2 active joints at Screening and Baseline, fever more than 38°C on at least one day within 14 consecutive days before the Screening Visit, and an erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) at Screening. OR At least 4 active joints at Screening and Baseline and an ESR or hsCRP > ULN at Screening.
- Must have inadequate response to previous treatment with nonsteroidal anti-inflammatory drugs and/or systemic glucocorticoids, as judged by the investigator.
- For Cohort 1, participants must not have had previous treatment with any IL-6 inhibitor. For Cohort 2, participants must have an intolerance or inadequate response to an IL-6 inhibitor as judged by the investigator.
Note: For Cohort 1, participants must be ages 2 to < 18 years old in countries where SC tocilizumab is not approved for sJIA.
- Has any type of juvenile idiopathic arthritis (JIA), other than sJIA, as defined by the ILAR criteria, and must not have a history or presence of any other autoimmune inflammatory condition other than sJIA.
- Has uncontrolled severe systemic disease and/or impeding or active macrophage activation syndrome within 1 month prior to Baseline.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Tocilizumab Tocilizumab Participants will receive tocilizumab for 52 weeks. Cohort 1 Upadacitinib Upadacitinib Participants will receive upadacitinib for 52 weeks. Cohort 2 Upadacitinib Upadacitinib Participants will receive upadacitinib for 52 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 30 Response At Week 12 ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 30 Response is defined as absence of fever \[\> 38°C\] in the previous 1 week preceding evaluation and improvement of ≥ 30% of the 6 variables of the JIA core set with no more than 1 variable worsening by \> 30%.
Number of Participants with Adverse Events (AEs) Up to Approximately Week 52 An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
- Secondary Outcome Measures
Name Time Method Change from Baseline in Number of Joints with Limitation of Motion Week 12 Change from Baseline in Number of Joints with Limitation of Motion
Change from Baseline in Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Week 12 The CHAQ-DI consists of 30 items and assesses function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 5 response options ranging from no difficulty to unable to do, scored 0 to 3, and not applicable.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 50 Response Week 12 ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 50 Response is defined as absence of fever \[\> 38°C\] in the previous 1 week preceding evaluation and improvement of ≥ 50% of the 6 variables of the JIA core set.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 70 Response Week 12 ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 70 Response is defined as absence of fever \[\> 38°C\] in the previous 1 week preceding evaluation and improvement of ≥ 70% of the 6 variables of the JIA core set.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 90 Response Week 12 ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 90 Response is defined as absence of fever \[\> 38°C\] in the previous 1 week preceding evaluation and improvement of ≥ 90% of the 6 variables of the JIA core set.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 100 Response Week 12 ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 100 Response is defined as absence of fever \[\> 38°C\] in the previous 1 week preceding evaluation and improvement of ≥ 100% of the 6 variables of the JIA core set.
Change from Baseline in Number of Joints with Active Arthritis Week 12 Change from Baseline in Number of Joints with Active Arthritis
Change From Baseline in Patient's Global Assessment (PtGA) Week 12 Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) Week 12 Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) Week 12 High sensitivity C-reactive protein was analyzed by a central laboratory. The median percent change from baseline in CRP is assessed at each time point.
Percentage of Participants with Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA) Week 12 Absence of fever (\> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA)
Change from Baseline in Glucocorticoid Dose Week 12 Change from Baseline in Glucocorticoid Dose
Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS27-CRP) Week 12 Juvenile Arthritis Disease Activity Score (JADAS27-CRP) will be assessed
Percentage of Participants Achieving Inactive Disease (ID) Status by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP Week 12 Inactive Disease (ID) status by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.
Percentage of Participants Achieving Minimal Disease Activity (MDA) by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP Week 12 Minimal Disease Activity (MDA) by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.
Percentage of Participants Achieving Clinical Remission by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP Week 12 Clinical Remission by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.
Trial Locations
- Locations (38)
New York Medical College /ID# 253437
🇺🇸Valhalla, New York, United States
Levine Children's Hospital /ID# 253491
🇺🇸Charlotte, North Carolina, United States
Randall Children's Hospital /ID# 251829
🇺🇸Portland, Oregon, United States
Monash Health - Monash Medical Centre /ID# 251691
🇦🇺Clayton, Victoria, Australia
Royal Children's Hospital /ID# 251663
🇦🇺Parkville, Victoria, Australia
Landeskrankenhaus Bregenz /ID# 266317
🇦🇹Bregenz, Vorarlberg, Austria
CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 251769
🇧🇷Juiz de Fora, Minas Gerais, Brazil
Hospital Sao Paulo /ID# 251765
🇧🇷Sao Paulo, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 251764
🇧🇷Sao Paulo, Brazil
The Children's Hospital of Chongqing Medical University /ID# 251539
🇨🇳Chongqing, Chongqing, China
Children'S Hospital Of Soochow University /ID# 251755
🇨🇳Suzhou, Jiangsu, China
Xi'an Children's Hospital /ID# 251693
🇨🇳Xi'an, Shaanxi, China
Children's Hospital of Fudan University /ID# 251619
🇨🇳Shanghai, Shanghai, China
The Children's Hospital of Zhejiang University School of Medicine /ID# 251754
🇨🇳Hangzhou, Zhejiang, China
Universitaetsklinikum Freiburg /ID# 253288
🇩🇪Freiburg, Baden-Wuerttemberg, Germany
Asklepios Klinik Sankt Augustin /ID# 251565
🇩🇪Sankt Augustin, Nordrhein-Westfalen, Germany
St. Josef-Stift Sendenhorst /ID# 268680
🇩🇪Sendenhorst, Nordrhein-Westfalen, Germany
Hamburger Zentrum fuer Kinder- und Jugendrheumatologie /ID# 251564
🇩🇪Hamburg, Germany
Semmelweis Egyetem /ID# 266750
🇭🇺Budapest, Hungary
Azienda Ospedaliero Universitaria Meyer /ID# 251775
🇮🇹Florence, Firenze, Italy
IRCCS Istituto Giannina Gaslini /ID# 251776
🇮🇹Genoa, Genova, Italy
Hyogo Prefectural Kobe Children's Hospital /ID# 251649
🇯🇵Kobe-shi, Hyogo, Japan
St. Marianna University Hospital /ID# 251623
🇯🇵Kawasaki-shi, Kanagawa, Japan
Niigata University Medical & Dental Hospital /ID# 251538
🇯🇵Niigata-shi, Niigata, Japan
Osaka Medical and Pharmaceutical University Hospital /ID# 252092
🇯🇵Takatsuki-shi, Osaka, Japan
Institute of Science Tokyo Hospital /ID# 251505
🇯🇵Bunkyo-ku, Tokyo, Japan
CREA de Guadalajara SC /ID# 252917
🇲🇽Guadalajara, Jalisco, Mexico
Universitair Medisch Centrum Utrecht /ID# 267435
🇳🇱Utrecht, Netherlands
Hospital Sant Joan de Deu /ID# 251353
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Universitario y Politecnico La Fe /ID# 251352
🇪🇸Valencia, Spain
Queen Silvia Children's Hosp /ID# 251318
🇸🇪Gothenburg, Vastra Gotalands Lan, Sweden
National Taiwan University Hospital /ID# 267387
🇨🇳Taipei City, Taipei, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 267390
🇨🇳Taoyuan City, Taiwan
Gazi University Medical Faculty /ID# 253677
🇹🇷Ankara, Turkey
Istanbul University Istanbul Medical Faculty /ID# 251652
🇹🇷Istanbul, Turkey
Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi /ID# 251651
🇹🇷Istanbul, Turkey
Umraniye Training and Res Hosp /ID# 251653
🇹🇷Istanbul, Turkey
Great Ormond Street Children's Hospital /ID# 251512
🇬🇧London, Greater London, United Kingdom