Clinical trial NCT01904279: A Study of Subcutaneously (SC) Administered Tocilizumab (TCZ) in Participants With Polyarticular-Course Juvenile Idiopathic Arthritis (pJIA)
Official title: A Phase Ib, Open-Label, Multicenter Study to Investigate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab Following Subcutaneous Administration to Patients With Polyarticular Juvenile Idiopathic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-07-22
Enrollment: 52
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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
* Active uveitis at screening
* Inadequate hematologic, renal or liver function
* Prior stem cell transplant at any time

Primary outcomes:
measure: Minimum Serum Concentration (Cmin) of TCZ at Steady State
timeFrame: Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
measure: Area Under the Curve at Steady-state Over a 12-week Interval (AUC12weeks) of TCZ Treatment
timeFrame: Pre-dose (Hour 0) up to 2016 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
measure: Maximum Serum Concentration (Cmax) of TCZ at Steady State
timeFrame: Pre-dose (Hour 0) up to 2520 hours post Day 1 dose (detailed timeframe is provided in outcome description section)
Secondary outcomes:
measure: Change From Baseline in Serum Interleukin-6 (IL-6) Levels
timeFrame: 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
measure: Change From Baseline in Soluble IL-6 Receptor Levels
timeFrame: 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
measure: Change From Baseline in C-Reactive Protein (CRP) Levels
timeFrame: Baseline, Weeks 4, 6, 9, 12,18, 20, 27, 28, 36, 44, 45, 51, 52
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline, Week 4, 6, 9, 12, 18, 20, 27, 28, 36, 44, 45, 51, 52
measure: Percentage of Participants With Anti-TCZ Antibodies of Neutralizing Potential
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Hartford
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Hackensack
country: United States
state: New Jersey
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Westmead
country: Australia
state: New South Wales
city: Parkville
country: Australia
state: Victoria
city: Rio de Janeiro
country: Brazil
state: RJ
city: Rio de Janeiro
country: Brazil
state: RJ
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Le Kremlin Bicêtre
country: France
city: Berlin
country: Germany
city: Freiburg
country: Germany
city: Sankt Augustin
country: Germany
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Firenze
country: Italy
state: Toscana
city: Monterrey
country: Mexico
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Esplugas de Llobregat
country: Spain
state: Barcelona
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Bristol
country: United Kingdom
city: Liverpool
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.