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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01904292
Collaborator
(none)
52
Enrollment
42
Locations
1
Arm
45.9
Actual Duration (Months)
1.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
N/A
Intervention Model:
Single Group 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 Systemic Juvenile Idiopathic Arthritis
Actual Study Start Date :
Aug 15, 2013
Actual Primary Completion Date :
Jun 13, 2017
Actual Study Completion Date :
Jun 13, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tocilizumab

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
Subcutaneous 162 mg dose QW or Q2W for 52 weeks
Other Names:
  • RoActemra/Actemra

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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]

    3. 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 Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. 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]

    5. 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]

    6. Safety: Percentage of Participants with At Least 1 Adverse Event [57 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    • 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

    • Macrophage activation syndrome (MAS) within 3 months of the screening visit

    • Inadequate hematologic, renal or liver function

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Hospital Research Institute Little Rock Arkansas United States 72202
    2 Connecticut Children's Medical Center; 5E Clinical Trials Unit Hartford Connecticut United States 06106
    3 Ann & Robert H. Lurie Children's Hospital of Chicago; Division of Rheumatology Chicago Illinois United States 60611
    4 The University of Chicago;Department of Pediatrics Chicago Illinois United States 60649
    5 Hackensack University Medical Center; Pediatric Rheumatology Hackensack New Jersey United States 07601
    6 Levine Children's Hospital; Divison of Pediatric Rheumatology; Department of Pediatrics Charlotte North Carolina United States 28203
    7 Duke University Durham North Carolina United States 27710
    8 Cincinnati Children'S Hospital Medical Center; Division of Rheumatology Cincinnati Ohio United States 45229-3039
    9 Cleveland Clinic Fndn Cleveland Ohio United States 44195
    10 University of Utah; Immunology/Rheumatology/Allergy Salt Lake City Utah United States 84109
    11 Seattle Children's Hospital Seattle Washington United States 98105
    12 Hospital Gral de Niños Pedro Elizalde Buenos Aires Argentina 1270
    13 Hospital de Ninos de la Santisima Trinidad; Reumatologia Infantil Cordoba Argentina 5000
    14 Westmead Hospital; Paediatric Rheumatology Westmead New South Wales Australia 2145
    15 Royal Children'S Hospital; Paediatric Rheumatology Parkville Victoria Australia 3052
    16 Hospital das Clinicas - FMUSP Ribeirao Preto; Pediatria - Imunologia e Reumatologia Ribeirao preto. SP Brazil 14048-900
    17 Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia Sao Paulo SP Brazil 05403-000
    18 Universidade Federal de Sao Paulo - UNIFESP Sao Paulo SP Brazil 22793-080
    19 Alberta Children'S Hospital Calgary Alberta Canada T3B 6A8
    20 Children'S Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1
    21 Hospital For Sick Children Toronto Ontario Canada M5G 1X8
    22 CH de Bicêtre; Pediatrie Generale Le Kremlin Bicêtre France 94275
    23 Charité Campus; Virchow Klinikum Berlin Berlin Germany 13353
    24 Uniklinikum Freiburg Zentrum für Kinder- und Jugendmedizin; Pädiatrische Infektio- u. Rheumatologie Freiburg Germany 79106
    25 Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie Sankt Augustin Germany 53757
    26 Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina Roma Lazio Italy 00165
    27 Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS Genova Liguria Italy 16147
    28 Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1° Firenze Toscana Italy 50139
    29 Hospital Infantil de México "Federico Gomez"; Rheumatology Mexico Mexico 06720
    30 Cliditer SA de CV Miexico City Mexico 06700
    31 Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria Monterrey Mexico 64460
    32 FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences Moscow Russian Federation 115522
    33 SI Sceintific children health center RAMS Moscow Russian Federation 119991
    34 Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica Esplugas DE Llobregat Barcelona Spain 08950
    35 Hospital Infantil Universitario Niño Jesus, Servicio Reumatologia Madrid Spain 28009
    36 Hospital Ramon y Cajal ; Servicio de Reumatologia Madrid Spain 28034
    37 Hospital de La Paz; Unidad de Reumatologia Pediatrica Madrid Spain 28046
    38 Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica Valencia Spain 46026
    39 Bristol Royal Hospital For Children Bristol United Kingdom BS2 8BJ
    40 Alder Hey Children's NHS Foundation Trust Liverpool United Kingdom L12 2AP
    41 Great Ormond Street Hospital; Somers Clinical Research Facility London United Kingdom WC1N 3JH
    42 Nottingham Children's Hospital Nottingham United Kingdom NG7 2UH

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01904292
    Other Study ID Numbers:
    • WA28118
    • 2012-003490-26
    First Posted:
    Jul 22, 2013
    Last Update Posted:
    Nov 20, 2017
    Last Verified:
    Nov 1, 2017
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Juvenile

    Study Results

    No Results Posted as of Nov 20, 2017