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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01904292




Registration number
NCT01904292
Ethics application status
Date submitted
14/06/2013
Date registered
22/07/2013
Date last updated
20/11/2017

Titles & IDs
Public title
A Study of Subcutaneously Administered Tocilizumab in Participants With Systemic Juvenile Idiopathic Arthritis
Scientific 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
Secondary ID [1] 0 0
2012-003490-26
Secondary ID [2] 0 0
WA28118
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Juvenile Idiopathic Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tocilizumab

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.


Treatment: Drugs: Tocilizumab
Subcutaneous 162 mg dose QW or Q2W for 52 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Tocilizumab
Timepoint [1] 0 0
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 outcome [2] 0 0
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Tocilizumab
Timepoint [2] 0 0
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 outcome [3] 0 0
Pharmacokinetics: Minimum Plasma Concentration (Cmin) of Tocilizumab
Timepoint [3] 0 0
Weight <30 kg: predose (0h) on Days 0 and 84. Weight >= 30 kg: predose (0h) on Days 0 and 91
Secondary outcome [1] 0 0
Pharmacodynamics: Serum Interleukin-6 (IL6) Levels
Timepoint [1] 0 0
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 outcome [2] 0 0
Pharmacodynamics: Soluble IL-6 Receptor (sIL-6R) Levels
Timepoint [2] 0 0
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 outcome [3] 0 0
Pharmacodynamics: Serum C-Reactive Protein (CRP) Levels
Timepoint [3] 0 0
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 outcome [4] 0 0
Pharmacodynamics: Serum Erythrocyte Sedimentation Rate (ESR)
Timepoint [4] 0 0
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 outcome [5] 0 0
Pharmacodynamics: Percentage of Participants with Anti-Tocilizumab Antibodies
Timepoint [5] 0 0
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 outcome [6] 0 0
Safety: Percentage of Participants with At Least 1 Adverse Event
Timepoint [6] 0 0
57 weeks

Eligibility
Key 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
Minimum age
1 Year
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/06/2017
Sample size
Target
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Westmead Hospital; Paediatric Rheumatology - Westmead
Recruitment hospital [2] 0 0
Royal Children'S Hospital; Paediatric Rheumatology - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Cordoba
Country [11] 0 0
Brazil
State/province [11] 0 0
SP
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
France
State/province [14] 0 0
Le Kremlin Bicêtre
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Freiburg
Country [17] 0 0
Germany
State/province [17] 0 0
Sankt Augustin
Country [18] 0 0
Italy
State/province [18] 0 0
Lazio
Country [19] 0 0
Italy
State/province [19] 0 0
Liguria
Country [20] 0 0
Italy
State/province [20] 0 0
Toscana
Country [21] 0 0
Mexico
State/province [21] 0 0
Mexico
Country [22] 0 0
Mexico
State/province [22] 0 0
Miexico City
Country [23] 0 0
Mexico
State/province [23] 0 0
Monterrey
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Moscow
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Spain
State/province [27] 0 0
Valencia
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Bristol
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Liverpool
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01904292
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries