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

NCT01904279 | Completed Phase 1 Results

• 2 other identifiers: WA281172012-003486-18
• Study Type: interventional
• Target: 52
• Locations: 12 countries
• Sites: 35

Brief Summary

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

Conditions

Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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 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)

  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

Study Arms (2)

TCZ SC 162 mg Q3W

EXPERIMENTAL

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

TCZ SC 162 mg Q2W

EXPERIMENTAL

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

Interventions

Tocilizumab DRUG

Participants will receive 162 mg of TCZ as SC injection Q3W or Q2W for 52 weeks

Also known as: RoActemra/Actemra

TCZ SC 162 mg Q2W; TCZ SC 162 mg Q3W

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (35)

Unknown Facility

Hartford, Connecticut, 06106, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

Charlotte, North Carolina, 28203, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45229-3039, United States

Location

Unknown Facility

Tulsa, Oklahoma, 74135, United States

Location

Unknown Facility

Salt Lake City, Utah, 84109, United States

Location

Unknown Facility

Seattle, Washington, 98105, United States

Location

Unknown Facility

Buenos Aires, 1270, Argentina

Location

Unknown Facility

Westmead, New South Wales, 2145, Australia

Location

Unknown Facility

Parkville, Victoria, 3052, Australia

Location

Unknown Facility

Rio de Janeiro, Rio de Janeiro, 20551-030, Brazil

Location

Unknown Facility

Rio de Janeiro, Rio de Janeiro, 21941-912, Brazil

Location

Unknown Facility

São Paulo, São Paulo, 05403-000, Brazil

Location

Unknown Facility

São Paulo, São Paulo, 22793-080, Brazil

Location

Unknown Facility

Calgary, Alberta, T3B 6A8, Canada

Location

Unknown Facility

Ottawa, Ontario, K1H 8L1, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 1X8, Canada

Location

Unknown Facility

Le Kremlin-Bicêtre, 94275, France

Location

Unknown Facility

Berlin, 13353, Germany

Location

Unknown Facility

Freiburg im Breisgau, 79106, Germany

Location

Unknown Facility

Sankt Augustin, 53757, Germany

Location

Unknown Facility

Rome, Lazio, 00165, Italy

Location

Unknown Facility

Genoa, Liguria, 16147, Italy

Location

Unknown Facility

Florence, Tuscany, 50139, Italy

Location

Unknown Facility

Monterrey, 64460, Mexico

Location

Unknown Facility

Moscow, 115522, Russia

Location

Unknown Facility

Moscow, 119991, Russia

Location

Unknown Facility

Esplugas de Llobregat, Barcelona, 08950, Spain

Location

Unknown Facility

Madrid, 28034, Spain

Location

Unknown Facility

Madrid, 28046, Spain

Location

Unknown Facility

Bristol, BS2 8BJ, United Kingdom

Location

Unknown Facility

Liverpool, L12 2AP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33506875 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: July 22, 2013
• Study Start: July 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 14, 2017
• Results First Posted: March 16, 2017

Record last verified: 2017-05

Locations

AR (1); CA (3); AU (2); IT (3); RU (2); US (10); ES (3); GB (2); DE (3); ME (1); BR (4); FR (1)