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Phase 1 N=52 Treatment

A Study of Subcutaneously (SC) Administered Tocilizumab (TCZ) in Participants With Polyarticular-Course Juvenile Idiopathic Arthritis (pJIA)

Juvenile Idiopathic Arthritis

Enrolled (actual)
52
Serious AEs
5.8%
Results posted
Mar 2017
Primary outcome: Primary: Minimum Serum Concentration (Cmin) of TCZ at Steady State — 13.35; 12.71 Micrograms/milliliter (mcg/mL)

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Tocilizumab (Drug)
Age
Pediatric · 1+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
May 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Minimum Serum Concentration (Cmin) of TCZ at Steady State
13.35; 12.71
PRIMARY
Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment
2998; 1933
PRIMARY
Maximum Serum Concentration (Cmax) of TCZ at Steady State
62.44; 29.74
SECONDARY
Change From Baseline in Serum Interleukin-6 (IL-6) Levels
77.569; 10.567; -15.309; 4.575; -16.181; 11.932
SECONDARY
Change From Baseline in Soluble IL-6 Receptor Levels
140.4; 206.7; -4.04; 1.78; -1.45; 4.58
SECONDARY
Change From Baseline in C-Reactive Protein (CRP) Levels
3.391; 3.356; -2.187; -3; -2.368; -3.069
SECONDARY
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
15.9; 13; -7.0; -10.6; -7.2; -9.9
SECONDARY
Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential
3.7; 8.0

Summary

This open-label, multicenter study evaluated the pharmacokinetics, pharmacodynamics and safety of SC administered TCZ in participants with pJIA.

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
  • Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection or any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit
  • History of atypical tuberculosis (TB) or active TB requiring treatment within 2 years prior to screening visit
  • Positive purified protein derivative (PPD) at screen, unless treated with anti-TB therapy for at least 4 weeks prior to receiving study drug and chest radiograph is negative for active TB within 6 months of screening visit according to local practice
  • History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein-Barr virus within 2 months of the screening visit
  • Hepatitis B surface antigen or hepatitis C antibody positivity or chronic viral or autoimmune hepatitis
  • History of concurrent serious gastrointestinal disorders such as ulcer or inflammatory bowel disease, Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions
  • History of or current cancer or lymphoma
  • Uncontrolled diabetes mellitus with elevated glycosylated hemoglobin
  • Active uveitis at screening
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01904279). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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