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

• 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: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Tocilizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2013
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

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 Name: 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 Name: RoActemra/Actemra

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.

Secondary Outcome Measures :

1. 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.
2. 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 ]
3. 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 ]
4. 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.
5. Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential [ Time Frame: Baseline up to Week 52 ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• Inadequate hematologic, renal or liver function
• Prior stem cell transplant at any time

Contacts and Locations

Locations

United States, Connecticut

Hartford, Connecticut, United States, 06106

United States, Illinois

Chicago, Illinois, United States, 60611

Chicago, Illinois, United States, 60637

United States, New Jersey

Hackensack, New Jersey, United States, 07601

United States, North Carolina

Charlotte, North Carolina, United States, 28203

Durham, North Carolina, United States, 27710

United States, Ohio

Cincinnati, Ohio, United States, 45229-3039

United States, Oklahoma

Tulsa, Oklahoma, United States, 74135

United States, Utah

Salt Lake City, Utah, United States, 84109

United States, Washington

Seattle, Washington, United States, 98105

Argentina

Buenos Aires, Argentina, 1270

Australia, New South Wales

Westmead, New South Wales, Australia, 2145

Australia, Victoria

Parkville, Victoria, Australia, 3052

Brazil

Rio de Janeiro, RJ, Brazil, 20551-030

Rio de Janeiro, RJ, Brazil, 21941-912

Sao Paulo, SP, Brazil, 05403-000

Sao Paulo, SP, Brazil, 22793-080

Canada, Alberta

Calgary, Alberta, Canada, T3B 6A8

Canada, 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

Roma, Lazio, Italy, 00165

Genova, Liguria, Italy, 16147

Firenze, Toscana, Italy, 50139

Mexico

Monterrey, Mexico, 64460

Russian Federation

Moscow, Russian Federation, 115522

Moscow, Russian Federation, 119991

Spain

Esplugas de Llobregat, Barcelona, Spain, 08950

Madrid, Spain, 28034

Madrid, Spain, 28046

United Kingdom

Bristol, United Kingdom, BS2 8BJ

Liverpool, United Kingdom, L12 2AP

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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]

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01904279
• Other Study ID Numbers: WA28117; 2012-003486-18 ( EudraCT Number )
• First Posted: July 22, 2013
• Results First Posted: March 16, 2017
• Last Update Posted: June 14, 2017
• Last Verified: May 2017

Additional relevant MeSH terms:

Arthritis; Arthritis, Juvenile; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases