A Study of Tocilizumab in Chinese Participants With Systemic Juvenile Idiopathic Arthritis (sJIA)

Juvenile Idiopathic Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03301883
• Other study ID #: YA39368
• Status: Completed
• Phase: Phase 4
• Start date: April 26, 2018
• Est. completion date: August 5, 2022

Study information

• Verified date: January 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: August 5, 2022
• Est. primary completion date: September 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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-?]-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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Tocilizumab
Tocilizumab will be administered as per the schedule specified in the arm description.
• NSAIDs
Participants may receive NSAIDs up to the maximum recommended stable daily dose. Study protocol does not enforce any particular NSAID.
• CSs
Participants may receive CSs at a stable dose of 30 milligrams per day (mg/day) or 0.5 milligrams per kilogram per day (mg/kg/day), whichever is less. Study protocol does not enforce any particular CS.
• MTX
Participants may receive MTX at a stable dose of less than or equal to (</=) 20 milligrams per square meter (mg/m^2).

Locations

Country	Name	City	State
China	Beijing Children's Hospital, Capital Medical University; rheumatism	Beijing City
China	Capital Institute of Pediatrics	Beijing City
China	The First Hospital of Jilin University	Changchun City
China	Children's Hospital Chongqing Medical university	Chongqing City
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Pediatric Rheumatology division	Guangzhou City
China	The Children's Hospibal ZheJiang University School of Medicine	Hangzhou City
China	Chilren's hospital of nanjing medical university; Rheumatoid immunology	Nanjing
China	Children's Hospital of Fudan University	Shanghai
China	Shanghai Children's Medical Center; Renal rheumatology	Shanghai City
China	The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical College	Wenzhou

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 (JIA ACR30) Response With Absence of Fever, at Week 12		Week 12
Secondary	Percentage of Participants Achieving JIA ACR30 Response With Absence of Fever, at Week 52		Week 52
Secondary	Percentage of Participants With 30 Percent (%), 50%, 70%, and 90% Improvement From Baseline in JIA Core Set Parameters		Baseline, Weeks 12, 24, and 52
Secondary	Percentage of Participants With Inactive Disease Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)		Weeks 24 and 52
Secondary	Percentage of Participants With Clinical Remission Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)		Week 52
Secondary	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		Baseline, Weeks 12, 24, and 52
Secondary	Mean Glucocorticoid Dose		Baseline up to Week 52
Secondary	Mean Methotrexate (MTX) Dose		Baseline up to Week 52
Secondary	Change From Baseline in Glucocorticoid Dose		From Baseline to Week 52
Secondary	Change From Baseline in MTX Dose		From Baseline to Week 52
Secondary	Pain Visual Analog Scale (VAS) Score		Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Change From Baseline in Pain VAS Score		Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Percentage of Participants Who Discontinue Permitted Concomitant Medication for sJIA		Baseline up to Week 52
Secondary	Percentage of Participants With Adverse Events (AEs)		Baseline up to end of study (up to Week 60)