Clinical trial NCT00095173: BMS-188667 in Children and Adolescents With Juvenile Rheumatoid Arthritis
Official title: A Phase III, Multi-Center, Multi-National, Randomized Withdrawal Study to Evaluate the Safety and Efficacy of BMS-188667 in Children and Adolescents With Active Polyarticular Juvenile Rheumatoid Arthritis (JRA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Rheumatoid Arthritis
Keywords: Juvenile Idiopathic Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2004-11-02
Enrollment: 214
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of the clinical research study is to assess the safety of treating children and juvenile subjects with BMS-188667 (Abatacept). In addition, the study will assess the effectiveness of BMS-188667 in reducing disease activity of Juvenile Rheumatoid Arthritis (JRA) or Juvenile Idiopathic Arthritis (JIA) as measured by the time to occurrence of disease flare.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Juvenile Rheumatoid Arthritis or Juvenile Idiopathic Arthritis;
* Current active arthritis;
* Failed treatment with at least one disease modifying anti-rheumatic drug (DMARD);
* Subjects must discontinue use of any DMARD other than methotrexate prior to the first dose of study medication

Exclusion Criteria:

* Presence of infection or history of frequent acute or chronic infections;
* Joint replacement surgery required during the study or history of surgery on more than 5 joints;
* Live vaccines within 3 months of the first dose of study medication;
* Unresolved serious bacterial infection or chronic bacterial infection;
* Subjects who currently have intermittent fever due to JRA/JIA, rheumatoid rash, hepato-splenomegaly, pleuritis, pericarditis, or macrophage activation syndrome.

Primary outcomes:
measure: Time to Occurrence of Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease Flare During Double-Blind Phase (Period B)
timeFrame: Period B (Day 113 to Day 282)
Secondary outcomes:
measure: Number of Participants With a Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease With a Flare During Double-Blind Phase (Period B)
timeFrame: Period B (Day 113 to Day 282)
measure: Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Lead-In Phase (Period A)
timeFrame: Period A (Day 1 to Day 113)
measure: Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Double-Blind Phase (Period B)
timeFrame: Period B (Day 113 to Day 282)
measure: Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Phase (Period C)
timeFrame: Period C (Day 282 to end of study)
measure: Median Percent Change From Baseline in JRA/JIA Core Set Variables During Double-Blind Phase (Period B)
timeFrame: Period B (Day 113 to Day 282)
measure: Median Percent Change From Baseline in JRA/JIA Core Set Variables During Open-Label Phase (Period C)
timeFrame: Period C (Day 282 to end of study)
measure: Events of Special Interest During Open-Label Lead-In Phase (Period A), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
timeFrame: Period A (Day 1 to Day 113)
measure: Events of Special Interest During Double-Blind Phase (Period B), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
timeFrame: Period B (Day 113 to Day 282)
measure: Events of Special Interest During Open-Label Phase (Period C), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
timeFrame: Period C (Day 282 up to 56 days after the last dose of study medication)
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) Pediatric 30 (ACRP30), ACR Pediatric 50, ACR Pediatric 70, ACR Pediatric 90, and Inactive Disease Status Erythrocyte Sedimentation Rate (ESR) Response Rate
timeFrame: Day 113, Day 282, and Day 2047
measure: Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Lead-In Phase (Period A)
timeFrame: Period A (Day 1 to Day 113)
measure: Number of Treated Participants With Marked Laboratory Abnormalities During Double-Blind Phase (Period B)
timeFrame: Period B (Day 113 to Day 282)
measure: Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Phase (Period C)
timeFrame: Period C (Day 282 to end of study)
measure: Number of Participants With Anti-Abatacept or Anti-CTLA4 Positive Responses Over Time During Open-Label Phase (Period C)
timeFrame: Period C (Day 282 to 85 days after the last dose of study medication)
Other outcomes:
Locations:
city: Omaha
country: United States
state: Nebraska
city: Livingston
country: United States
state: New Jersey
city: New Hyde Park
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Bregenz
country: Austria
facility: Local Institution
city: Botucatu
country: Brazil
facility: Local Institution
city: Rio de Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Bremen
country: Germany
facility: Local Institution
city: Halle
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Firenze
country: Italy
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Trieste
country: Italy
facility: Local Institution
city: Guadalajara
country: Mexico
facility: Local Institution
city: Mexico City
country: Mexico
facility: Local Institution
city: Monterrey
country: Mexico
facility: Local Institution
city: Puebla
country: Mexico
facility: Local Institution
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lisboa
country: Portugal
facility: Local Institution
city: La Coruna
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Lausanne
country: Switzerland
facility: Local Institution
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: Lovell DJ, Ruperto N, Mouy R, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Chavez-Corrales J, Huemer C, Kivitz A, Blanco FJ, Foeldvari I, Hofer M, Huppertz HI, Job Deslandre C, Minden K, Punaro M, Block AJ, Giannini EH, Martini A; Pediatric Rheumatology Collaborative Study Group and the Paediatric Rheumatology International Trials Organisation. Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years. Arthritis Rheumatol. 2015 Oct;67(10):2759-70. doi: 10.1002/art.39234.
citation: Ruperto N, Lovell DJ, Li T, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Alcala JO, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace C, Alessio M, Quartier P, Cortis E, Eberhard A, Simonini G, Lemelle I, Chalom EC, Sigal LH, Block A, Covucci A, Nys M, Martini A, Giannini EH; Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1542-51. doi: 10.1002/acr.20283. Epub 2010 Jul 1.
citation: Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Chavez-Corrales J, Huemer C, Kivitz A, Blanco FJ, Foeldvari I, Hofer M, Horneff G, Huppertz HI, Job-Deslandre C, Loy A, Minden K, Punaro M, Nunez AF, Sigal LH, Block AJ, Nys M, Martini A, Giannini EH; Paediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010 Jun;62(6):1792-802. doi: 10.1002/art.27431.
citation: Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH; Paediatric Rheumatology INternational Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008 Aug 2;372(9636):383-91. doi: 10.1016/S0140-6736(08)60998-8. Epub 2008 Jul 14.