A Phase Ib, Open-Label, Multicenter Study to Investigate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Following Subcutaneous Administration to Patients With Systemic Juvenile Idiopathic Arthritis
Overview
- Phase
- Phase 1
- Intervention
- Tocilizumab
- Conditions
- Juvenile Idiopathic Arthritis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 52
- Locations
- 42
- Primary Endpoint
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This open-label, multicenter study will evaluate the pharmacokinetics, pharmacodynamics, and safety of subcutaneously administered tocilizumab in participants with Systemic Juvenile Idiopathic Arthritis (sJIA). Participants with body weight less than (<) 30 kilograms (kg) will receive subcutaneous (SC) tocilizumab dose every 2 weeks (Q2W) and participants with body weight greater than or equal to (>=) 30 kg will receive weekly (QW), for 52 weeks. Tocilizumab was administered every 10 days until pre-planned interim analysis was performed and changed to Q2W in participants with body weight <30 kg.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of sJIA according to the International League of Associations for Rheumatology (ILAR) classification
- •History of inadequate clinical response (in the opinion of the treating physician) to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids
- •If a participant has received previous treatment with any biologic agents other than tocilizumab, these must have been discontinued according to the timelines defined by protocol prior to the baseline visit
- •Participants currently receiving tocilizumab by the intravenous (IV) route of administration and with well-controlled disease do not require a period of discontinuation of IV tocilizumab and should have their first dose of SC tocilizumab administered on the date that their next IV tocilizumab infusion would be due
- •Concurrent treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (MTX), NSAIDs, and oral corticosteroids are permitted at the discretion of the investigator
- •Participants of reproductive potential must be willing to use highly effective contraceptive methods
Exclusion Criteria
- •Prior discontinuation of IV tocilizumab because of inadequate clinical response or safety events (including hypersensitivity)
- •Participants with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV tocilizumab
- •sJIA that is well controlled by any treatment agent other than tocilizumab (Juvenile Arthritis Disease Activity Score of 71 Joints \[JADAS-71\] less than or equal to \[\<=\] 3.8 with no fever)
- •Participants who are wheelchair-bound or bedridden
- •Any other auto-immune, rheumatic disease, or overlapping syndrome other than sJIA
- •Lack of recovery from recent surgery or an interval of \<6 weeks since surgery at the time of the screening visit
- •Females who are pregnant, lactating, or intending to become pregnant during study conduct
- •Any significant concurrent medical or surgical condition that would jeopardize the participant's safety or ability to complete the study
- •Known Human Immunodeficiency Virus (HIV) infection or other acquired forms of immune compromise or inborn conditions characterized by a compromised immune system
- •History of alcohol, drug, or chemical abuse within 6 months of screening
Arms & Interventions
Tocilizumab
Participants will receive SC dose of tocilizumab based on body weight; participants with \<30 kg will receive 162 milligrams (mg) of tocilizumab Q2W and those participants =\>30 kg will receive 162 mg of tocilizumab QW, for 52 weeks.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab
Time Frame: Age <2 years: 0 hours(h) on Days(D) 0,84; on D5,14,42,70,85,88,98,182,266, 364. Weight <30kg, Age>=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266, 364
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Tocilizumab
Time Frame: Age <2 years: 0h on D0,84; on D5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30 kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266,364
Pharmacokinetics: Minimum Plasma Concentration (Cmin) of Tocilizumab
Time Frame: Weight <30 kg: predose (0h) on Days 0 and 84. Weight >= 30 kg: predose (0h) on Days 0 and 91
Secondary Outcomes
- Pharmacodynamics: Soluble IL-6 Receptor (sIL-6R) Levels(Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364)
- Pharmacodynamics: Serum Interleukin-6 (IL6) Levels(Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364)
- Pharmacodynamics: Serum C-Reactive Protein (CRP) Levels(Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364)
- Pharmacodynamics: Serum Erythrocyte Sedimentation Rate (ESR)(Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364)
- Pharmacodynamics: Percentage of Participants with Anti-Tocilizumab Antibodies(Age <2 years: Days 0, 84, 182, 266, 364. Weight <30 kg, Age >=2 years: Days 0, 84, 182, 266, 364. Weight >=30 kg: Days 0, 91, 182, 266, 364)
- Safety: Percentage of Participants with At Least 1 Adverse Event(57 weeks)