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

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

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

Study Overview

• Status: Completed
• Conditions: Juvenile Idiopathic Arthritis
• Intervention / Treatment: Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1270
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
  • Victoria
    • Parkville, Victoria, Australia, 3052
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20551-030
    • Rio de Janeiro, RJ, Brazil, 21941-912
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
    • Sao Paulo, SP, Brazil, 22793-080
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
    • Toronto, Ontario, Canada, M5G 1X8
• France
  • Le Kremlin Bicêtre, France, 94275
• Germany
  • Berlin, Germany, 13353
  • Freiburg, Germany, 79106
  • Sankt Augustin, Germany, 53757
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00165
  • Liguria
    • Genova, Liguria, Italy, 16147
  • Toscana
    • Firenze, Toscana, Italy, 50139
• Mexico
  • Monterrey, Mexico, 64460
• Russian Federation
  • Moscow, Russian Federation, 115522
  • Moscow, Russian Federation, 119991
• Spain
  • Madrid, Spain, 28046
  • Madrid, Spain, 28034
  • Barcelona
    • Esplugas de Llobregat, Barcelona, Spain, 08950
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
  • Liverpool, United Kingdom, L12 2AP
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60611
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
  • Utah
    • Salt Lake City, Utah, United States, 84109
  • Washington
    • Seattle, Washington, United States, 98105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Tocilizumab; Participants will receive 162 mg of TCZ as SC injection Q3W or Q2W for 52 weeks; Other Names: RoActemra/Actemra
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.	Drug: Tocilizumab; Participants will receive 162 mg of TCZ as SC injection Q3W or Q2W for 52 weeks; Other Names: RoActemra/Actemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Serum Concentration (Cmin) of TCZ at Steady State	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.	Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment	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.	Pre-dose (Hour 0) up to 2016 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Maximum Serum Concentration (Cmax) of TCZ at Steady State	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.	Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Interleukin-6 (IL-6) Levels	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.	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 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 C-Reactive Protein (CRP) Levels		Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)	The ESR is an acute phase reactant and a measure of inflammation. A negative change from baseline indicates improvement.	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General 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-Perez N, Hsu JC, Wimalasundera S, Wells C, Bharucha K, Douglass W, Bao M, Mallalieu NL, Martini A, Lovell D, Benedetti F; Paediatric Rheumatology INternational Trials Organisation (PRINTO) and the Paediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2021 Oct 2;60(10):4568-4580. doi: 10.1093/rheumatology/keab047.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: June 14, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile
• Other Study ID Numbers: WA28117; 2012-003486-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No