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)

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified May 2023 by Bristol-Myers Squibb
Sponsor
Bristol-Myers Squibb
Information Provided by (Responsible Party)
Bristol-Myers Squibb
Clinicaltrials.gov Identifier
NCT01844518
Other Study ID Numbers:
IM101-301
First Submitted
April 28, 2013
First Posted
April 30, 2013
Results First Posted
February 22, 2016
Last Update Posted
July 11, 2023
Last Verified
May 2023

ClinicalTrials.gov processed this data on June 2023Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Active Polyarticular Juvenile Idiopathic Arthritis
Biological: Abatacept

Study Design

Study TypeInterventional
Actual Enrollment219 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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 Start DateAugust 29, 2013
Actual Primary Completion DateMarch 11, 2015
Actual Study Completion DateJanuary 31, 2023

Groups and Cohorts

Group/CohortIntervention/Treatment
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

Outcome Measures

Primary Outcome Measures
  1. 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.
Secondary Outcome Measures
  1. 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: 1. number of active joints 2. number of joints with limitation of motion (LOM) 3. physician global assessment of disease activity 4. parent global assessment of patient overall well-being 5. functional ability as measured by the Children's Health Assessment Questionnaire (CHAQ) 6. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsBristol-Myers Squibb
Locations
Local Institution - 0007 | Birmingham Alabama, United States, 35233-1711Local Institution - 0003 | Little Rock Arkansas, United States, 72202Local Institution - 0011 | Hartford Connecticut, United States, 06106Local Institution - 0009 | Chicago Illinois, United States, 60637Riley Hospital For Children | Indianapolis Indiana, United States, 46202University Of Kansas Medical Center | Kansas City Kansas, United States, 66160Local Institution - 0001 | Kansas City Missouri, United States, 64108Local Institution - 0002 | The Bronx New York, United States, 10467Local Institution - 0008 | Cincinnati Ohio, United States, 45229Local Institution - 0005 | Portland Oregon, United States, 97227Local Institution - 0004 | Salt Lake City Utah, United States, 84132Seattle Children'S Hospital | Seattle Washington, United States, 98105Local Institution - 0029 | Rosario Santa Fe Province, Argentina, 2000Local Institution - 0028 | San Miguel de Tucumán Tucumán Province, Argentina, 4000Local Institution - 0030 | Buenos Aires , Argentina, 1270Local Institution - 0064 | CABA , Argentina, 1427Local Institution - 0031 | Córdoba , Argentina, 5000Local Institution - 0037 | Brussels , Belgium, 1200Local Institution - 0036 | Ghent , Belgium, 9000Local Institution - 0049 | Leuven , Belgium, 3000Local Institution | Curitiba Paraná, Brazil, 80250-060Local Institution - 0038 | Porto Alegre Rio Grande do Sul, Brazil, 91350-200Local Institution - 0042 | São Paulo , Brazil, 04038-031Local Institution - 0040 | São Paulo , Brazil, 05403-000Local Institution - 0041 | São Paulo , Brazil, 05403-000Local Institution - 0018 | Bron , France, 69677Local Institution - 0016 | Le Kremlin-Bicêtre , France, 94275Local Institution - 0014 | Paris , France, 75743Local Institution - 0017 | Poitiers , France, 86021Local Institution - 0015 | Strasbourg , France, 67098Local Institution - 0044 | Bad Bramstedt , Germany, 24576Local Institution - 0045 | Berlin , Germany, 13353Local Institution - 0046 | Hamburg , Germany, 22081Local Institution - 0048 | Heidelberg , Germany, 69120Local Institution - 0047 | Sankt Augustin , Germany, 53757Local Institution - 0061 | Florence , Italy, 50139Local Institution | Genova , Italy, 16147Local Institution - 0022 | Milan , Italy, 20122Local Institution - 0062 | Naples , Italy, 80131Local Institution - 0060 | Guadalajara Jalisco, Mexico, 44620Local Institution - 0059 | Mexico City Mexico City, Mexico, 06720Local Institution - 0057 | Mexico City Mexico City, Mexico, 06726Local Institution - 0056 | Monterrey Nuevo León, Mexico, 64460Local Institution - 0058 | Mérida Yucatán, Mexico, 97133Local Institution - 0027 | Lima , Peru, 11Local Institution | Lima , Peru, 11Local Institution - 0025 | Lima , Peru, 27Local Institution - 0026 | Lima , Peru, 5Local Institution - 0068 | Tolyatti , Russia, 445039Local Institution - 0035 | Park West, Bloemfontein Free State, South Africa, 9301Local Institution - 0032 | Pretoria Gauteng, South Africa, 0002Local Institution - 0034 | Pretoria Gauteng, South Africa, 0084Local Institution - 0033 | Cape Town Western Cape, South Africa, 7500Local Institution - 0050 | Barcelona , Spain, 08950Local Institution - 0053 | Madrid , Spain, 28034Local Institution - 0055 | Madrid , Spain, 28041Local Institution - 0052 | Valencia , Spain, 46026
Investigators
Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb