Clinical trial NCT01844518: Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously (SC) in Children and Adolescents With Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Inadequate Response (IR) to Biologic or Non Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs)
Official title: A Phase 3 Multi-center, Open-Label Study to Evaluate Pharmacokinetics, Efficacy and Safety of Abatacept Administered Subcutaneously (SC) in Children and Adolescents With Active Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Inadequate Response (IR) to Biologic or Non Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Active Polyarticular Juvenile Idiopathic Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-05-01
Enrollment: 219
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 estimate Abatacept steady-state trough concentration (Cmin) at Day 113 in children and adolescents with pJIA


Eligibility criteria: Inclusion Criteria:

* JIA subjects (male or female), ages 2-17 years with active disease who had an insufficient therapeutic response or intolerance to at least one non biologic DMARD or Tumor Necrosis Factor (TNFα) antagonists for at least 3 months prior to screening
* Subjects with TNFα inadequate response (or prior biologic) will be restricted to 30% of the population
* Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease with ≥2 active joints and ≥2 joints with limitation of motion.

Exclusion Criteria:

* Subjects with other rheumatic diseases or major chronic inflammatory/immunologic diseases, active uveitis, systemic JIA with active systemic features (within a period of 6 months prior to enrollment), persistent Oligoarthritis JIA, or failed 3 or more TNFα antagonists or other biological DMARDs will be excluded.
* Active systemic disease: (ie, extra-articular features of systemic JIA including fever, rash, organomegaly) within a period of 6 months prior to randomization.
* Subjects who have failed more than two TNFα antagonists or other biologic DMARDs

Primary outcomes:
measure: Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17
timeFrame: Day 113
Secondary outcomes:
measure: Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30)
timeFrame: Day 113
measure: Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose
timeFrame: Days 57, 85 and 113
measure: Number of Participants With Adverse Events (AEs), Deaths, Serious AEs (SAEs) and AEs Leading to Discontinuation in the Short-Term Period for the 6-17 Year Age-Group Cohort
timeFrame: From first dose up to 56 days post last dose in the short-term period (initial 4-month treatment period)
measure: Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period
timeFrame: From first dose up to 56 days after last dose ( up to approximately 2 years)
measure: Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort
timeFrame: From first dose up to start of LT (for those continuing in long-term) or up to 168 days after the lost dose of study medication in the ST period (for those not entering in the long-term)
measure: Number of Participants With Positive Immunogenicity Response in the Cumulative Period
timeFrame: From first dose up to 6 months following treatment discontinuation (up to approximately 2 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0007
state: Alabama
city: Little Rock
country: United States
facility: Local Institution - 0003
state: Arkansas
city: Hartford
country: United States
facility: Local Institution - 0011
state: Connecticut
city: Chicago
country: United States
facility: Local Institution - 0009
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Kansas City
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Kansas City
country: United States
facility: Local Institution - 0001
state: Missouri
city: Bronx
country: United States
facility: Local Institution - 0002
state: New York
city: Cincinnati
country: United States
facility: Local Institution - 0008
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0005
state: Oregon
city: Salt Lake City
country: United States
facility: Local Institution - 0004
state: Utah
city: Seattle
country: United States
facility: Seattle Children'S Hospital
state: Washington
city: Rosario
country: Argentina
facility: Local Institution - 0029
state: Santa FE
city: San Miguel De Tucuman
country: Argentina
facility: Local Institution - 0028
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution - 0030
city: Caba
country: Argentina
facility: Local Institution - 0064
city: Cordoba
country: Argentina
facility: Local Institution - 0031
city: Bruxelles
country: Belgium
facility: Local Institution - 0037
city: Gent
country: Belgium
facility: Local Institution - 0036
city: Leuven
country: Belgium
facility: Local Institution - 0049
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution - 0038
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Local Institution - 0042
city: Sao Paulo
country: Brazil
facility: Local Institution - 0040
city: Sao Paulo
country: Brazil
facility: Local Institution - 0041
city: Bron Cedex
country: France
facility: Local Institution - 0018
city: Le Kremlin Bicetre Cedex
country: France
facility: Local Institution - 0016
city: Paris Cedex 15
country: France
facility: Local Institution - 0014
city: Poitiers
country: France
facility: Local Institution - 0017
city: Strasbourg Cedex
country: France
facility: Local Institution - 0015
city: Bad Bramstedt
country: Germany
facility: Local Institution - 0044
city: Berlin
country: Germany
facility: Local Institution - 0045
city: Hamburg
country: Germany
facility: Local Institution - 0046
city: Heidelberg
country: Germany
facility: Local Institution - 0048
city: Sankt Augustin
country: Germany
facility: Local Institution - 0047
city: Firenze
country: Italy
facility: Local Institution - 0061
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution - 0022
city: Napoli
country: Italy
facility: Local Institution - 0062
city: Mexico City
country: Mexico
facility: Local Institution - 0057
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0059
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution - 0060
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0056
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution - 0058
state: Yucatan
city: Lima
country: Peru
facility: Local Institution - 0027
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution - 0025
city: Lima
country: Peru
facility: Local Institution - 0026
city: Tolyatti
country: Russian Federation
facility: Local Institution - 0068
city: Park West, Bloemfontein
country: South Africa
facility: Local Institution - 0035
state: FREE State
city: Pretoria
country: South Africa
facility: Local Institution - 0032
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution - 0034
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution - 0033
state: Western CAPE
city: Barcelona
country: Spain
facility: Local Institution - 0050
city: Madrid
country: Spain
facility: Local Institution - 0053
city: Madrid
country: Spain
facility: Local Institution - 0055
city: Valencia
country: Spain
facility: Local Institution - 0052
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Ruperto N, Brunner HI, Tzaribachev N, Vega-Cornejo G, Louw I, Cimaz R, Dare J, Espada G, Faugier E, Ferrandiz M, Gerloni V, Quartier P, Silva CA, Wagner-Weiner L, Gandhi Y, Passarell J, Nys M, Wong R, Martini A, Lovell DJ; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO). Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis. J Rheumatol. 2021 Jul;48(7):1073-1081. doi: 10.3899/jrheum.200154. Epub 2021 Jan 15.
citation: Brunner HI, Tzaribachev N, Cornejo GV, Joos R, Gervais E, Cimaz R, Calvo Penades I, Cuttica R, Lutz T, Quartier P, Gandhi Y, Nys M, Wong R, Martini A, Lovell DJ, Ruperto N; Pediatric Rheumatology Collaborative Study Group and the Paediatric Rheumatology International Trials Organisation. Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2-5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept. Pediatr Rheumatol Online J. 2020 Feb 22;18(1):19. doi: 10.1186/s12969-020-0410-x.
citation: Brunner HI, Tzaribachev N, Vega-Cornejo G, Louw I, Berman A, Calvo Penades I, Anton J, Avila-Zapata F, Cuttica R, Horneff G, Foeldvari I, Keltsev V, Kingsbury DJ, Viola DO, Joos R, Lauwerys B, Paz Gastanaga ME, Rama ME, Wouters C, Bohnsack J, Breedt J, Fischbach M, Lutz T, Minden K, Miraval T, Ally MMTM, Rubio-Perez N, Solau Gervais E, van Zyl R, Li X, Nys M, Wong R, Banerjee S, Lovell DJ, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study. Arthritis Rheumatol. 2018 Jul;70(7):1144-1154. doi: 10.1002/art.40466. Epub 2018 May 20.