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A Study of Subcutaneously (SC) Administered Tocilizumab (TCZ) in Participants With Polyarticular-Course Juvenile Idiopathic Arthritis (pJIA) (JIGSAW 117)

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ClinicalTrials.gov Identifier: NCT01904279
Recruitment Status : Completed
First Posted : July 22, 2013
Results First Posted : March 16, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 14, 2013
First Posted Date  ICMJE July 22, 2013
Results First Submitted Date  ICMJE January 24, 2017
Results First Posted Date  ICMJE March 16, 2017
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE July 2013
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
  • Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: 14 weeks ]
  • Pharmacokinetics: Serum concentrations (Cmin/Cmax) [ Time Frame: 14 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
  • Change From Baseline in Serum Interleukin-6 (IL-6) Levels [ Time Frame: 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 ]
    IL-6 is a cytokine associated with disease activity in juvenile idiopathic arthritis (JIA) including the polyarticular juvenile idiopathic arthritis (pJIA) subset. It is found in high levels in the synovial fluid and is associated with indicators of inflammatory activity.
  • Change From Baseline in Soluble IL-6 Receptor Levels [ Time Frame: 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 [ Time Frame: Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52 ]
  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Week 4, 6, 9, 12, 18, 20, 27, 28, 36, 44, 45, 51, 52 ]
    The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement.
  • Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential [ Time Frame: Baseline up to Week 52 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
  • Pharmacodynamics: Serum interleukin-6 (IL6)/soluble IL-6 receptor (sIL-6R) levels [ Time Frame: 14 weeks ]
  • Pharmacodynamics: C-reactive protein (CRP) [ Time Frame: 52 weeks ]
  • Pharmacodynamics: Erythrocyte sedimentation rate (ESR) [ Time Frame: 52 weeks ]
  • Pharmacodynamics: Incidence of anti-TCZ antibodies [ Time Frame: 52 weeks ]
  • Safety: Incidence of adverse events [ Time Frame: 57 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Subcutaneously (SC) Administered Tocilizumab (TCZ) in Participants With Polyarticular-Course Juvenile Idiopathic Arthritis (pJIA)
Official Title  ICMJE 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
Brief Summary This open-label, multicenter study evaluated the pharmacokinetics, pharmacodynamics and safety of SC administered TCZ in participants with pJIA.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Juvenile Idiopathic Arthritis
Intervention  ICMJE Drug: Tocilizumab
Participants will receive 162 mg of TCZ as SC injection Q3W or Q2W for 52 weeks
Other Name: RoActemra/Actemra
Study Arms  ICMJE
  • Experimental: 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: Drug: Tocilizumab
  • Experimental: 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: Drug: Tocilizumab
Publications * Ruperto N, Brunner HI, Ramanan AV, Horneff G, Cuttica R, Henrickson M, Anton J, Boteanu AL, Penades IC, Minden K, Schmeling H, Hufnagel M, Weiss JE, Pardeo M, Nanda K, Roth J, Rubio-Pérez N, Hsu JC, Wimalasundera S, Wells C, Bharucha K, Douglass W, Bao M, Mallalieu NL, Martini A, Lovell D, De Benedetti F; Paediatric Rheumatology INternational Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2021 Jan 28. pii: keab047. doi: 10.1093/rheumatology/keab047. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 1, 2016)
52
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2013)
48
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Inadequate hematologic, renal or liver function
  • Prior stem cell transplant at any time
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   France,   Germany,   Italy,   Mexico,   Russian Federation,   Spain,   United Kingdom,   United States
Removed Location Countries Peru,   Poland
 
Administrative Information
NCT Number  ICMJE NCT01904279
Other Study ID Numbers  ICMJE WA28117
2012-003486-18 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP