A Phase Ib, Open-Label, Multicenter Study to Investigate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Following Subcutaneous Administration to Patients With Polyarticular Juvenile Idiopathic Arthritis
Overview
- Phase
- Phase 1
- Intervention
- Tocilizumab
- Conditions
- Juvenile Idiopathic Arthritis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 52
- Primary Endpoint
- Maximum Serum Concentration (Cmax) of TCZ at Steady State
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This open-label, multicenter study evaluated the pharmacokinetics, pharmacodynamics and safety of SC administered TCZ in participants with pJIA.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ages 1 year (12 years for participants in Russia) up to and including 17 years at screening
- •Diagnosis of pJIA according to International League of Associations for Rheumatology classification
- •Rheumatoid factor (RF)-positive pJIA
- •RF-negative pJIA
- •Extended oligoarticular JIA with a polyarticular course
- •History of inadequate clinical response (in the opinion of the treating physician) to or inability to tolerate methotrexate (MTX)
- •Participants currently receiving TCZ by the intravenous (IV) route of administration and with well-controlled disease do not require a period of discontinuation of IV TCZ and should have their first dose of SC TCZ administered on the date that their next IV TCZ infusion would be due. Participants participating in the study may be either naive to TCZ therapy or may be switching from IV to SC. The total number of participants switching from IV TCZ must account for no more than 50 percent (%) of the total participant number. To account for the baseline TCZ concentrations in these participants, information on the last 4 IV TCZ infusions prior to baseline will be collected
- •Concurrent treatment with disease-modifying antirheumatic drugs (DMARDs) (including MTX), nonsteroidal anti-inflammatory drugs (NSAIDs), and oral corticosteroids are permitted at the discretion of the investigator
- •Females of childbearing potential and non-sterile males with female partner of childbearing potential must agree to use effective contraception as defined by protocol
Exclusion Criteria
- •Prior discontinuation of IV TCZ 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 TCZ
- •pJIA that is well controlled by any treatment agent other than TCZ (Juvenile Arthritis Disease Activity Score 71 \[JADAS-71\] less than or equal to (\< / =) 3.8)
- •Participants who are wheelchair-bound or bedridden
- •Any other auto-immune, rheumatic disease, or overlapping syndrome other than the permitted pcJIA subsets
- •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
TCZ SC 162 mg Q3W
Participants with body weight less than (\<) 30 kilograms (kg) will be administered 162 milligrams (mg) of TCZ as a SC injection every 3 weeks (Q3W) for 52 weeks.
Intervention: Tocilizumab
TCZ SC 162 mg Q2W
Participants with body weight greater than or equal to (\>/=) 30 kg will be administered 162 mg of TCZ as a SC injection every 2 weeks (Q2W) for 52 weeks.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Maximum Serum Concentration (Cmax) of TCZ at Steady State
Time Frame: Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, ,2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose.
Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment
Time Frame: Pre-dose (Hour 0) up to 2016 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016 hours post Day 1 dose (additionally at 6, 12, 48, 120 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016 post Day 1 dose.
Minimum Serum Concentration (Cmin) of TCZ at Steady State
Time Frame: Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Detailed timeframe for TCZ SC 162 mg Q3W arm: pre-dose (Hour 0), 96, 504, 1008, 2016, 2022, 2064, 2112, 2160, 2520 hours post Day 1 dose (additionally at 6, 12, 48, 120, 2028 hours post Day 1 dose in participants \>/=2 years old). Detailed timeframe for TCZ SC 162 mg Q2W arm: pre-dose (Hour 0), 6, 12, 48, 120, 336, 672, 1008, 2016, 2022, 2028, 2040, 2064, 2112, 2160, 2520 hours post Day 1 dose.
Secondary Outcomes
- Change From Baseline in Serum Interleukin-6 (IL-6) Levels(Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52)
- Change From Baseline in C-Reactive Protein (CRP) Levels(Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52)
- Change From Baseline in Soluble IL-6 Receptor Levels(Baseline, Days 0.25, 0.5, 2, 4, 5, 84.25, 84.5, 85, 86, 88, 90; Weeks 2, 3, 4, 6, 12, 14, 15, 27, 28, 36, 44, 52)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, Week 4, 6, 9, 12, 18, 20, 27, 28, 36, 44, 45, 51, 52)
- Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential(Baseline up to Week 52)