Clinical trial NCT03301883: A Study of Tocilizumab in Chinese Participants With Systemic Juvenile Idiopathic Arthritis (sJIA)
Official title: A Phase IV, Multicenter, Single-Arm, Open-Label Study to Assess the Efficacy and Safety of Tocilizumab in Chinese Patients With Systemic Juvenile Idiopathic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-10-04
Enrollment: 62
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase IV, multicenter, single-arm, open-label study will evaluate the efficacy and safety of tocilizumab in Chinese participants with sJIA with persistent activity and an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs) and steroid therapy.


Eligibility criteria: Inclusion Criteria:

* Participants meeting International League of Associations for Rheumatology (ILAR) classification for sJIA
* Greater than (\>) 6 months of documented persistent sJIA activity prior to screening
* Active disease
* hsCRP \>4.3 milligrams per liter (mg/L) or 0.43 milligrams per deciliter (mg/dL)
* Participant who has recovered from any symptomatic serositis for at least 30 days prior to the screening visit, and requires a dose of CSs at baseline of \</=30 mg/day or \</=0.5 mg/kg/day, whichever is less
* Participants meeting one of the following: Participant who is not receiving MTX or discontinued MTX \>/=4 weeks prior to baseline visit; participant who has been taking MTX \>/=12 weeks immediately prior to the baseline visit and on a stable dose of \</=20 mg/m\^2 for \>/=8 weeks prior to the baseline visit, together with either folic acid or folinic acid according to local standard of care
* Participant who was never treated with biologics or, if was previously treated with biologics, discontinued etanercept (or Yisaipu, Qiangke, or Anbainuo) \>/=2 weeks, infliximab or adalimumab \>/=8 weeks, anakinra \>/=1 week, or abatacept \>/=12 weeks prior to the baseline visit
* Participant who is not currently receiving oral CSs, or is taking oral CSs at a stable dose for \>/=2 weeks prior to the baseline visit at \</=30 mg/day or \</=0.5 mg/kg/day, whichever is less
* Participant who is not taking NSAIDs, or taking \</=1 type of NSAID at a stable dose for \>/=2 weeks prior to the baseline visit and is less than or equal to the maximum recommended daily dose

Exclusion Criteria:

* Wheelchair bound or bedridden participant
* Any other autoimmune, rheumatic disease, or overlap syndrome other than sJIA
* Participant who is not fully recovered from recent surgery or \<6 weeks since surgery at the time of screening visit; or planned surgery during the initial 12 weeks of the study
* Lack of peripheral venous access
* Any significant concurrent medical or surgical condition that would jeopardize the participant's safety or ability to complete the trial
* Evidence of serious uncontrolled concomitant diseases
* Asthma for which the participant has required the use of oral or parenteral CSs for \>/=2 weeks within 6 months prior to the baseline visit
* Known human immunodeficiency (HIV) infection or other acquired forms of immune compromise or congenital conditions characterized by a compromised immune system
* Any active acute, subacute, chronic, or recurrent bacterial, mycobacterial, viral, or systemic fungal infection or opportunistic infection
* Any major episode of infection requiring hospitalization or treatment during screening, treatment with IV antibiotics completing within 4 weeks of the screening visit, or oral antibiotics completing within 2 weeks of the screening visit
* History of atypical tuberculosis (TB)
* Active TB requiring treatment within 2 years prior to screening visit
* Positive purified protein derivative (PPD) or T-spot test (interferon-gamma \[IFN-γ\]-based test) at screen
* Positive for latent TB
* History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein-Barr virus (EBV) within 2 months of the screening visit
* Hepatitis B surface antigen (Ag)- or hepatitis C antibody (Ab)-positive
* History of macrophage activation syndrome (MAS) within 3 months prior to the screening visit
* Evidence of active malignant disease or diagnosed malignancies
* Uncontrolled diabetes mellitus
* Previous treatment with tocilizumab
* Intra-articular, intramuscular, IV, or long-acting CSs administration within 28 days prior to the baseline visit
* Treatment with non-biologic disease-modifying antirheumatic drugs (DMARDs; other than MTX) within 6 weeks prior to the baseline visit
* Treatment with leflunomide that was not followed by standardized cholestyramine washout and documented to be below the limit of detection prior to the baseline visit
* Treatment with cyclophosphamide, etoposide (VP16) and statins within 90 days prior to the baseline visit
* Treatment with growth hormone and androgens within 4 weeks prior to the baseline visit
* Administration of IV immunoglobulin within 28 days prior to the baseline visit
* Treatment with any cell-depleting therapies
* Stem cell transplant at any time
* Participant who has received live or attenuated vaccines within 4 weeks prior to the baseline visit, or intending to receive while on study drug or 3 months following the last dose of study drug

Primary outcomes:
measure: Percentage of Participants Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 (JIA ACR30) Response With Absence of Fever, at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving JIA ACR30 Response With Absence of Fever, at Week 52
timeFrame: Week 52
measure: Percentage of Participants With 30 Percent (%), 50%, 70%, and 90% Improvement From Baseline in JIA Core Set Parameters
timeFrame: Baseline, Weeks 12, 24, and 52
measure: Percentage of Participants With Inactive Disease Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)
timeFrame: Weeks 24 and 52
measure: Percentage of Participants With Clinical Remission Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)
timeFrame: Week 52
measure: Percentage of Participants With an Elevated High-Sensitivity C-Reactive Protein (hsCRP) Levels at Baseline Who Have Normal hsCRP Levels at Weeks 12, 24, and 52
timeFrame: Baseline, Weeks 12, 24, and 52
measure: Mean Glucocorticoid Dose
timeFrame: Baseline up to Week 52
measure: Mean Methotrexate (MTX) Dose
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Glucocorticoid Dose
timeFrame: From Baseline to Week 52
measure: Change From Baseline in MTX Dose
timeFrame: From Baseline to Week 52
measure: Pain Visual Analog Scale (VAS) Score
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change From Baseline in Pain VAS Score
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants Who Discontinue Permitted Concomitant Medication for sJIA
timeFrame: Baseline up to Week 52
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to end of study (up to Week 60)
Other outcomes:
Locations:
city: Beijing City
country: China
facility: Capital Institute of Pediatrics
city: Beijing City
country: China
facility: Beijing Children's Hospital, Capital Medical University; rheumatism
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chongqing City
country: China
facility: Children's Hospital Chongqing Medical university
city: Guangzhou City
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Pediatric Rheumatology division
city: Hangzhou City
country: China
facility: The Children's Hospibal ZheJiang University School of Medicine
city: Nanjing
country: China
facility: Chilren's hospital of nanjing medical university; Rheumatoid immunology
city: Shanghai City
country: China
facility: Shanghai Children's Medical Center; Renal rheumatology
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Wenzhou
country: China
facility: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical College
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: