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

Juvenile Idiopathic Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904292
• Other study ID #: WA28118
• Secondary ID: 2012-003490-26
• Status: Completed
• Phase: Phase 1
• First received: June 14, 2013
• Last updated: November 16, 2017
• Start date: August 15, 2013
• Est. completion date: June 13, 2017

Study information

• Verified date: November 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 13, 2017
• Est. primary completion date: June 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Tocilizumab
Subcutaneous 162 mg dose QW or Q2W for 52 weeks

Locations

Country	Name	City	State
Argentina	Hospital Gral de Niños Pedro Elizalde	Buenos Aires
Argentina	Hospital de Ninos de la Santisima Trinidad; Reumatologia Infantil	Cordoba
Australia	Royal Children'S Hospital; Paediatric Rheumatology	Parkville	Victoria
Australia	Westmead Hospital; Paediatric Rheumatology	Westmead	New South Wales
Brazil	Hospital das Clinicas - FMUSP Ribeirao Preto; Pediatria - Imunologia e Reumatologia	Ribeirao preto.	SP
Brazil	Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia	Sao Paulo	SP
Brazil	Universidade Federal de Sao Paulo - UNIFESP	Sao Paulo	SP
Canada	Alberta Children'S Hospital	Calgary	Alberta
Canada	Children'S Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Hospital For Sick Children	Toronto	Ontario
France	CH de Bicêtre; Pediatrie Generale	Le Kremlin Bicêtre
Germany	Charité Campus; Virchow Klinikum Berlin	Berlin
Germany	Uniklinikum Freiburg Zentrum für Kinder- und Jugendmedizin; Pädiatrische Infektio- u. Rheumatologie	Freiburg
Germany	Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie	Sankt Augustin
Italy	Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°	Firenze	Toscana
Italy	Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS	Genova	Liguria
Italy	Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina	Roma	Lazio
Mexico	Hospital Infantil de México "Federico Gomez"; Rheumatology	Mexico
Mexico	Cliditer SA de CV	Miexico City
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria	Monterrey
Russian Federation	FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences	Moscow
Russian Federation	SI Sceintific children health center RAMS	Moscow
Spain	Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica	Esplugas DE Llobregat	Barcelona
Spain	Hospital de La Paz; Unidad de Reumatologia Pediatrica	Madrid
Spain	Hospital Infantil Universitario Niño Jesus, Servicio Reumatologia	Madrid
Spain	Hospital Ramon y Cajal ; Servicio de Reumatologia	Madrid
Spain	Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica	Valencia
United Kingdom	Bristol Royal Hospital For Children	Bristol
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
United Kingdom	Great Ormond Street Hospital; Somers Clinical Research Facility	London
United Kingdom	Nottingham Children's Hospital	Nottingham
United States	Levine Children's Hospital; Divison of Pediatric Rheumatology; Department of Pediatrics	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago; Division of Rheumatology	Chicago	Illinois
United States	The University of Chicago;Department of Pediatrics	Chicago	Illinois
United States	Cincinnati Children'S Hospital Medical Center; Division of Rheumatology	Cincinnati	Ohio
United States	Cleveland Clinic Fndn	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center; Pediatric Rheumatology	Hackensack	New Jersey
United States	Connecticut Children's Medical Center; 5E Clinical Trials Unit	Hartford	Connecticut
United States	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	University of Utah; Immunology/Rheumatology/Allergy	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  France,  Germany,  Italy,  Mexico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Safety: Percentage of Participants with At Least 1 Adverse Event		57 weeks