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)

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)

The purpose of this study is to estimate Abatacept steady-state trough concentration (Cmin) at Day 113 in children and adolescents with pJIA

Study Overview

• Status: Completed
• Conditions: Active Polyarticular Juvenile Idiopathic Arthritis
• Intervention / Treatment: Biological: Abatacept

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1270
    • Local Institution - 0030
  • Caba, Argentina, 1427
    • Local Institution - 0064
  • Cordoba, Argentina, 5000
    • Local Institution - 0031
  • Santa FE
    • Rosario, Santa FE, Argentina, 2000
      • Local Institution - 0029
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution - 0028
• Belgium
  • Bruxelles, Belgium, 1200
    • Local Institution - 0037
  • Gent, Belgium, 9000
    • Local Institution - 0036
  • Leuven, Belgium, 3000
    • Local Institution - 0049
• Brazil
  • Sao Paulo, Brazil, 04038-031
    • Local Institution - 0042
  • Sao Paulo, Brazil, 05403-000
    • Local Institution - 0040
  • Sao Paulo, Brazil, 05403-000
    • Local Institution - 0041
  • Parana
    • Curitiba, Parana, Brazil, 80250-060
      • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Local Institution - 0038
• France
  • Bron Cedex, France, 69677
    • Local Institution - 0018
  • Le Kremlin Bicetre Cedex, France, 94275
    • Local Institution - 0016
  • Paris Cedex 15, France, 75743
    • Local Institution - 0014
  • Poitiers, France, 86021
    • Local Institution - 0017
  • Strasbourg Cedex, France, 67098
    • Local Institution - 0015
• Germany
  • Bad Bramstedt, Germany, 24576
    • Local Institution - 0044
  • Berlin, Germany, 13353
    • Local Institution - 0045
  • Hamburg, Germany, 22081
    • Local Institution - 0046
  • Heidelberg, Germany, 69120
    • Local Institution - 0048
  • Sankt Augustin, Germany, 53757
    • Local Institution - 0047
• Italy
  • Firenze, Italy, 50139
    • Local Institution - 0061
  • Genova, Italy, 16147
    • Local Institution
  • Milano, Italy, 20122
    • Local Institution - 0022
  • Napoli, Italy, 80131
    • Local Institution - 0062
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06720
      • Local Institution - 0059
    • Mexico City, Distrito Federal, Mexico, 06726
      • Local Institution - 0057
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44620
      • Local Institution - 0060
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution - 0056
  • Yucatan
    • Merida, Yucatan, Mexico, 97133
      • Local Institution - 0058
• Peru
  • Lima, Peru, 11
    • Local Institution - 0027
  • Lima, Peru, 11
    • Local Institution
  • Lima, Peru, 27
    • Local Institution - 0025
  • Lima, Peru, 5
    • Local Institution - 0026
• Russian Federation
  • Tolyatti, Russian Federation, 445039
    • Local Institution - 0068
• South Africa
  • FREE State
    • Park West, Bloemfontein, FREE State, South Africa, 9301
      • Local Institution - 0035
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0002
      • Local Institution - 0032
    • Pretoria, Gauteng, South Africa, 0084
      • Local Institution - 0034
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7500
      • Local Institution - 0033
• Spain
  • Barcelona, Spain, 08950
    • Local Institution - 0050
  • Madrid, Spain, 28041
    • Local Institution - 0055
  • Madrid, Spain, 28034
    • Local Institution - 0053
  • Valencia, Spain, 46026
    • Local Institution - 0052
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1711
      • Local Institution - 0007
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Local Institution - 0003
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Local Institution - 0011
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0009
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Local Institution - 0001
  • New York
    • Bronx, New York, United States, 10467
      • Local Institution - 0002
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Local Institution - 0008
  • Oregon
    • Portland, Oregon, United States, 97227
      • Local Institution - 0005
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Local Institution - 0004
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short and Long Terms: Orencia; Short Term: Orencia 50 mg/mL, 87.5 mg/mL, 125 mg/mL pre-filled syringes subcutaneously (0.4 mL/0.7 mL/1.0 mL) weekly for 4 months Long term: Orencia 50 mg/mL, 87.5 mg/mL, 125 mg/mL pre-filled syringes subcutaneously (0.4 mL/0.7 mL/1.0 mL) weekly for 20 months	Biological: Abatacept; Other Names: Orencia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17	Trough concentration of abatacept (reported as geometric mean of Cmin) in all pharmacokinetic (PK)-evaluable participants. Cmin is reported in microgram per milliliter (µg/mL). Desired target therapeutic Cmin should be >= 10 µg/mL.	Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants (Ages 6 to 17) Achieving American College of Rheumatology Pediatric 30 Response (ACRp30)	ACRp30 is defined as ≥30% improvement in at least 3 of the 6 juvenile idiopathic arthritis (JIA) core set variables: number of active joints; number of joints with limitation of motion (LOM); physician global assessment of disease activity; parent global assessment of patient overall well-being; functional ability as measured by the Children's Health Assessment Questionnaire (CHAQ); C-reactive protein (CRP). In addition to the above condition, to be considered a responder participants cannot have ≥30% worsening in more than 1 of the 3 remaining JIA core set variables for which improvement was not observed.	Day 113
Abatacept Trough Concentration (Cmin) in Participants Ages 6 to 17 by Weight Tier Dose	Evaluation of the trough concentration of abatacept (reported as geometric mean of Cmin) in all pk-evaluable participants at Days 57, 85 and 113. Weight-tiered dosing groups are based on the first dose the participant received. Cmin is reported in microgram per milliliter (µg/mL). Here 'n' number analyzed signifies participants who were evaluable for each time point.	Days 57, 85 and 113
Number of Participants With Adverse Events (AEs), Deaths, Serious AEs and AEs Leading to Discontinuation in the Cumulative Period	An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose which results in death, is life threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect.	From first dose up to 56 days after last dose ( up to approximately 2 years)
Number of Participants With Positive Immunogenicity Response in the Cumulative Period	Overall number of participants with either a positive immunogenicity response for 'CTLA4 and possibly Ig' or 'Ig and/or Junction Region' relative to baseline. Sample draws for immunogenicity were scheduled at specific study days while on treatment for all subjects and at follow-up visits 28, 85, and 168 days after the last abatacept dose regardless of whether they discontinued early in the short term (ST) or long term (LT) period, elected not to enter the LT period, or completed both ST and LT periods.	From first dose up to 6 months following treatment discontinuation (up to approximately 2 years)
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	An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. A SAE is any untoward medical occurrence that at any dose which results in death, is life threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect.	From first dose up to 56 days post last dose in the short-term period (initial 4-month treatment period)
Number of Participants With Positive Immunogenicity Response in the Short-Term Period for the 6-17 Year Age-Group Cohort	Overall number of participants with either a positive immunogenicity response for 'CTLA4 and possibly Ig' or 'Ig and/or Junction Region' relative to baseline. Sample draws for immunogenicity were scheduled at specific study days while on treatment for all subjects and at follow-up visits 28, 85, and 168 days after the last abatacept dose for those subjects who discontinued from the short term (ST) period (initial 4-month treatment period) or completed the ST study without continuing abatacept treatment.	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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2013
• Primary Completion (Actual): March 12, 2015
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimated): May 1, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-301; 2012-003195-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No