A Study of Subcutaneously Administered Tocilizumab in Participants With Systemic Juvenile Idiopathic Arthritis

NCT01904292 | Completed Phase 1

• 2 other identifiers: WA281182012-003490-26
• Study Type: interventional
• Target: 52
• Locations: 12 countries
• Sites: 42

Brief Summary

This open-label, multicenter study will evaluate the pharmacokinetics, pharmacodynamics, and safety of subcutaneously administered tocilizumab in participants with Systemic Juvenile Idiopathic Arthritis (sJIA). Participants with body weight less than (\<) 30 kilograms (kg) will receive subcutaneous (SC) tocilizumab dose every 2 weeks (Q2W) and participants with body weight greater than or equal to (\>=) 30 kg will receive weekly (QW), for 52 weeks. Tocilizumab was administered every 10 days until pre-planned interim analysis was performed and changed to Q2W in participants with body weight \<30 kg.

Conditions

Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab

  Age <2 years: 0 hours(h) on Days(D) 0,84; on D5,14,42,70,85,88,98,182,266, 364. Weight <30kg, Age>=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266, 364

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Tocilizumab

  Age <2 years: 0h on D0,84; on D5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on D0,84; on D2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30 kg: 0,6,12h on D0, 91; on D2,4,7,14,28,56,92,93,95,96,98,182,266,364

• Pharmacokinetics: Minimum Plasma Concentration (Cmin) of Tocilizumab

  Weight <30 kg: predose (0h) on Days 0 and 84. Weight >= 30 kg: predose (0h) on Days 0 and 91

Secondary Outcomes (6)

• Pharmacodynamics: Serum Interleukin-6 (IL6) Levels

  Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364

• Pharmacodynamics: Soluble IL-6 Receptor (sIL-6R) Levels

  Age<2 years: 0h on Days 0,84; Days 5,14,42,70,85,88,98,182,266,364. Weight <30 kg, Age >=2 years: 0,6,12h on Days 0,84; Days 2,5,14,42,56,70,86,87,88,90,98,182,266,364. Weight >=30kg: 0,6,12h on Days 0,91;Days 2,4,7,14,28,56,92,93,95,96,98,182,266,364

• Pharmacodynamics: Serum C-Reactive Protein (CRP) Levels

  Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364

• Pharmacodynamics: Serum Erythrocyte Sedimentation Rate (ESR)

  Age <2years: Days 0,14,28,42,70,84,98,126, 154,182,210,238,266,294,322,350,364. Weight <30 kg, Age >=2years: Days 0,14,28,42,70, 98,126,154,182,210,238,266,294,322,350,364. Weight >=30kg: Days 0,7,14,21,28,42, 56,70,84,91,95,96,98,182,266,294,322,350,364

• Pharmacodynamics: Percentage of Participants with Anti-Tocilizumab Antibodies

  Age <2 years: Days 0, 84, 182, 266, 364. Weight <30 kg, Age >=2 years: Days 0, 84, 182, 266, 364. Weight >=30 kg: Days 0, 91, 182, 266, 364

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Participants will receive SC dose of tocilizumab based on body weight; participants with \<30 kg will receive 162 milligrams (mg) of tocilizumab Q2W and those participants =\>30 kg will receive 162 mg of tocilizumab QW, for 52 weeks.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Subcutaneous 162 mg dose QW or Q2W for 52 weeks

Also known as: RoActemra/Actemra

Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Diagnosis of sJIA according to the International League of Associations for Rheumatology (ILAR) classification
• History of inadequate clinical response (in the opinion of the treating physician) to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids
• If a participant has received previous treatment with any biologic agents other than tocilizumab, these must have been discontinued according to the timelines defined by protocol prior to the baseline visit
• Participants currently receiving tocilizumab by the intravenous (IV) route of administration and with well-controlled disease do not require a period of discontinuation of IV tocilizumab and should have their first dose of SC tocilizumab administered on the date that their next IV tocilizumab infusion would be due
• Concurrent treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate (MTX), NSAIDs, and oral corticosteroids are permitted at the discretion of the investigator
• Participants of reproductive potential must be willing to use highly effective contraceptive methods

You may not qualify if:

• Prior discontinuation of IV tocilizumab 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 tocilizumab
• sJIA that is well controlled by any treatment agent other than tocilizumab (Juvenile Arthritis Disease Activity Score of 71 Joints \[JADAS-71\] less than or equal to \[\<=\] 3.8 with no fever)
• Participants who are wheelchair-bound or bedridden
• Any other auto-immune, rheumatic disease, or overlapping syndrome other than sJIA
• 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 TB test at screening unless treated with anti-TB therapy for at least 4 weeks prior to receiving study drug
• 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 (42)

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, 72202, United States

Location

Connecticut Children's Medical Center; 5E Clinical Trials Unit

Hartford, Connecticut, 06106, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago; Division of Rheumatology

Chicago, Illinois, 60611, United States

Location

The University of Chicago;Department of Pediatrics

Chicago, Illinois, 60649, United States

Location

Hackensack University Medical Center; Pediatric Rheumatology

Hackensack, New Jersey, 07601, United States

Location

Levine Children's Hospital; Divison of Pediatric Rheumatology; Department of Pediatrics

Charlotte, North Carolina, 28203, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, 45229-3039, United States

Location

Cleveland Clinic Fndn

Cleveland, Ohio, 44195, United States

Location

University of Utah; Immunology/Rheumatology/Allergy

Salt Lake City, Utah, 84109, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, 1270, Argentina

Location

Hospital de Ninos de la Santisima Trinidad; Reumatologia Infantil

Córdoba, 5000, Argentina

Location

Westmead Hospital; Paediatric Rheumatology

Westmead, New South Wales, 2145, Australia

Location

Royal Children'S Hospital; Paediatric Rheumatology

Parkville, Victoria, 3052, Australia

Location

Hospital das Clinicas - FMUSP Ribeirao Preto; Pediatria - Imunologia e Reumatologia

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia

São Paulo, São Paulo, 05403-000, Brazil

Location

Universidade Federal de Sao Paulo - UNIFESP

São Paulo, São Paulo, 22793-080, Brazil

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Children'S Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CH de Bicêtre; Pediatrie Generale

Le Kremlin-Bicêtre, 94275, France

Location

Charité Campus; Virchow Klinikum Berlin

Berlin, 13353, Germany

Location

Uniklinikum Freiburg Zentrum für Kinder- und Jugendmedizin; Pädiatrische Infektio- u. Rheumatologie

Freiburg im Breisgau, 79106, Germany

Location

Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie

Sankt Augustin, 53757, Germany

Location

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, 00165, Italy

Location

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

Genoa, Liguria, 16147, Italy

Location

Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°

Florence, Tuscany, 50139, Italy

Location

Hospital Infantil de México "Federico Gomez"; Rheumatology

México, 06720, Mexico

Location

Cliditer SA de CV

Miexico City, 06700, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

Monterrey, 64460, Mexico

Location

FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences

Moscow, 115522, Russia

Location

SI Sceintific children health center RAMS

Moscow, 119991, Russia

Location

Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica

Esplugas de Llobregat, Barcelona, 08950, Spain

Location

Hospital Infantil Universitario Niño Jesus, Servicio Reumatologia

Madrid, 28009, Spain

Location

Hospital Ramon y Cajal ; Servicio de Reumatologia

Madrid, 28034, Spain

Location

Hospital de La Paz; Unidad de Reumatologia Pediatrica

Madrid, 28046, Spain

Location

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, 46026, Spain

Location

Bristol Royal Hospital For Children

Bristol, BS2 8BJ, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Great Ormond Street Hospital; Somers Clinical Research Facility

London, WC1N 3JH, United Kingdom

Location

Nottingham Children's Hospital

Nottingham, NG7 2UH, 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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: July 22, 2013
• Study Start: August 15, 2013
• Primary Completion: June 13, 2017
• Study Completion: June 13, 2017
• Last Updated: November 20, 2017

Record last verified: 2017-11

Locations

BR (3); IT (3); ME (3); AR (2); GB (4); CA (3); FR (1); DE (3); US (11); ES (5); AU (2); RU (2)