Clinical trial NCT02277444: A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy
Official title: A Multicenter, Open-Label Trial of Intravenous Golimumab, a Human Anti-TNFα Antibody, in Pediatric Subjects With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Juvenile
Keywords: Methotrexate
Anti-TNFα Antibody
Golimumab
Pediatric Participants
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-10-29
Enrollment: 130
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of golimumab administered intravenously (IV) to pediatric participants with polyarticular (affects 5 or more joints) juvenile (an onset before age 16) idiopathic (of unknown cause) arthritis (joint pain) (pJIA) manifested by greater than or equal to (\>=) 5 joints with active arthritis despite methotrexate (MTX) therapy for \>= 2 months.

Detailed description: This is a single arm, Open-label (all people know the identity of the intervention), multi-center (when more than one hospital or medical school team work on a medical research study) study to determine the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), efficacy (effectiveness) and safety of intravenous golimumab in participants with pJIA despite current treatment with methotrexate (MTX). The study will consist of 3 parts: Screening Phase (6 weeks); an Open-label Treatment Phase (consists of golimumab and MTX treatment for 52 weeks, wherein after Week 28, MTX dose change is allowed); Long-term Extension Phase (after Week 52 through Week 252) and Extended Treatment Period (after week 252). The maximal study duration for a participant will not exceed 832 weeks. All the eligible participants will be administered golimumab IV infusion and commercial MTX. Blood samples will be collected for evaluation of pharmacokinetics of study treatment. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis must be made per Juvenile Idiopathic Arthritis (JIA) International League of Associations for Rheumatology (ILAR) diagnostic criteria and the onset of disease must have been before the participant's 16th birthday
* Failure or inadequate response to at least a 2 month course of methotrexate (MTX) before screening
* Participants must have greater than or equal to (\>=) 5 joints with active arthritis at screening and at Week 0 as defined by American College of Rheumatology (ACR) criteria (that is, a joint with either swelling, or in the absence of swelling, limited range of motion associated with pain on motion or tenderness)
* Participants must have a screening C-reactive protein (CRP) of \>=0.1 milligram (mg)/deciliter (dL) with the exception of approximately 30 percent (%) of the study population
* Participants must have active polyarticular juvenile idiopathic arthritis (pJIA) despite current use of oral, intramuscular, or subcutaneous MTX for \>=2 months before screening. For participants with body surface area (BSA) less than (\<)1.67 meter square (m\^2), the MTX dose must be between 10 to 30 milligram per meter square (mg/m\^2) per week and stable for \>=4 weeks before screening. For participants with BSA \>=1.67 m\^2, the MTX dose must be a minimum of 15 mg/week and must be stable for \>=4 weeks before screening. In situations where there is documented intolerance of doses greater than (\>)10 mg/m\^2 weekly (for participants with BSA \<1.67 m\^2) or \>=15 mg/week (for participants with BSA \>=1.67 m\^2); or where documented country or site regulations prohibit use of \>=15 mg of MTX per week in participants with BSA \>=1.67 m\^2, participants may be entered into the trial on a lower dose of MTX

Exclusion Criteria:

* Participant has initiated disease-modifying antirheumatic drugs (DMARDs) and/or immunosuppressive therapy within 4 weeks prior to first study agent administration
* Participant has been treated with intra-articular, intramuscular or intravenous corticosteroids (including intramuscular corticotropin) during the 4 weeks before first study agent administration
* Participant has been treated with any therapeutic agent targeted at reducing Interleukin (IL)-12 or IL 23, including but not limited to ustekinumab and ABT-874, within 3 months before first study agent administration
* Participant has been treated with natalizumab, efalizumab, or therapeutic agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) during the 12 months before first study agent administration, or have evidence at screening of persistent depletion of the targeted lymphocyte after receiving any of these agents
* Participant has been treated with alefacept within 3 months before first study agent administration
* If a participant has been previously treated with an anti-tumor necrosis factor alpha (TNF alpha) agent, the reason for discontinuation of the anti-TNF alpha agent cannot have been a severe or serious adverse event consistent with the class of anti-TNF alpha agents

Primary outcomes:
measure: Serum Trough Concentration (C-trough) of Golimumab
timeFrame: Week 28
measure: Bayesian Area Under Curve at Steady State (AUCss) Over an 8-week Dosing Interval at Week 28
timeFrame: Week 28
Secondary outcomes:
measure: Serum Trough Concentration (C-trough) at Week 52
timeFrame: Week 52
measure: Baysesian Area Under Curve at Steady State (AUCss) at Week 52
timeFrame: Week 52
Other outcomes:
Locations:
city: San Diego
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: New Hyde Park
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Avon
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Austin
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: San Miguel De Tucuman
country: Argentina
city: Botucatu
country: Brazil
city: Campinas
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Región Metropolitana De Santia
country: Chile
city: Haifa
country: Israel
city: Kfar-Saba
country: Israel
city: Petach-Tikva
country: Israel
city: Chihuahua
country: Mexico
city: Ciudad De Mexico
country: Mexico
city: Guadalajara
country: Mexico
city: Mosco2
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saratov
country: Russian Federation
city: Togliatti
country: Russian Federation
city: Ufa
country: Russian Federation
city: Cape Town
country: South Africa
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Leu JH, Shiff NJ, Clark M, Bensley K, Lomax KG, Berezny K, Nelson RM, Zhou H, Xu Z. Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations. Paediatr Drugs. 2022 Nov;24(6):699-714. doi: 10.1007/s40272-022-00533-y. Epub 2022 Sep 28.
citation: Ruperto N, Brunner HI, Pacheco-Tena C, Louw I, Vega-Cornejo G, Spindler AJ, Kingsbury DJ, Schmeling H, Borzutzky A, Cuttica R, Inman CJ, Malievskiy V, Scott C, Keltsev V, Terreri MT, Viola DO, Xavier RM, Fernandes TAP, Velazquez MDRM, Henrickson M, Clark MB, Bensley KA, Li X, Lo KH, Leu JH, Hsu CH, Hsia EC, Xu Z, Martini A, Lovell DJ; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO). Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2021 Oct 2;60(10):4495-4507. doi: 10.1093/rheumatology/keab021.