Efficacy, Safety, Pharmacokinetics and Immunogenicity Study of Abatacept Administered Intravenously to Treat Active Polyarticular-course Juvenile Idiopathic Arthritis in Japan

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

Abatacept

About this trial

This is an interventional treatment trial for Juvenile Idiopathic Arthritis

Eligibility Criteria

4 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects who have a history of an inadequate therapeutic response or intolerance in the opinion of the examining physician to at least one biologics or Methotrexate (MTX).
Diagnosis of Juvenile Idiopathic Arthritis (JIA) by International League of Associations for Rheumatology (ILAR) criteria as oligoarticular, polyarticular Rheumatoid Factor (RF+), polyarticular (RF-), or systemic with a polyarticular-course.
Men and women, ages 4 to 17 years, inclusive at enrollment.
Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease as defined by:
1. ≥2 active joints (e.g. presence of swelling, or if no swelling is present, limitation of motion (LOM) accompanied by pain, tenderness, or both) at screening and at Week 0 (Day 1).
2. ≥2 joints with LOM at screening and at Week 0 (Day 1).

Exclusion Criteria:

Systemic onset JIA with any of the following manifestations within the last 6 months prior to enrollment: intermittent fever due to JIA, rheumatoid rash, hepatosplenomegaly, pleuritis, pericarditis, or macrophage activation syndrome.
Presence of any other rheumatic disease or major chronic infectious/inflammatory/immunologic disease (e.g. inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, hypogammaglobulinemia, or systemic lupus erythematosus, etc.)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abatacept

Arm Description

Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study

Outcomes

Primary Outcome Measures

Percentage of Participants Experiencing a American College of Rheumatology (ACR) Pediatric 30 Response at Week 16

American College of Rheumatology (ACR) pediatric (PED) 30 response was defined as '≥30% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. JIA core set variables defined as the number of active joints, number of joints with Limit of Motion (LOM), physician's global assessment of disease severity, patient global assessment of overall well being, parent assessment of physical function, and acute phase reactant value. A non-responder imputation was applied.

Secondary Outcome Measures

Percentage of Participants Experiencing a American College of Rheumatology Pediatric 50, 70, 90 Response or Inactive Disease at Week 16

ACR PED 50 response is defined as '≥50% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 70 response is defined as '≥70% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 90 response is defined as '≥90% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Inactive disease status is defined as no active joints, physician's global assessment of disease severity equal or less than 10mm and C-reactive protein (CRP) within normal limits (0.3 mg/dL). A non-responder imputation is applied. mm=millimeter; mg/dL=milligrams/deciliter

Median Percentage of Improvement From Baseline in Physical Function as Assessed by the Childhood Health Assessment Questionnaire (CHAQ) Disability Index at Week 16

Physical function was evaluated using the disability section of the Childhood Health Assessment Questionnaire (CHAQ). The questionnaire was derived from the adult HAQ. The disability section assessed physical functions in 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities. The questions were evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 =unable to do. Higher scores indicate greater dysfunction. A disability index was calculated as the mean of the 8 functional scales. The percentage of Improvement from baseline was calculated using the following equation: (Baseline value - Post-baseline value) / Baseline value x 100.

Number of Participants With Death, Serious Adverse Events (SAEs), Drug-Related SAEs, Discontinuation Due to Drug-Related SAEs, Drug-Related Adverse Events (AEs), and Discontinuation Due to Drug-Related AEs During the Short Term Period

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. SAEs also include hospitalizations for elective surgical procedures. Drug-related=related or missing relationship to study drug. Data includes all events from the date of the first dose of the study drug up to 56 days post the last dose of the study drug in the short-term period or start of the long-term period, whichever occurred first.

Maximum Observed Concentration (Cmax) of Abatacept During the Short Term Period

Cmax was obtained from the serum concentration versus time data after intravenous administration of abatacept. Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

Trough Observed Concentration (Ctrough) of Abatacept During the Short Term Period

Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

Number of Participants With Positive Immunogenicity During the Short Term Period

A positive immunogenicity response for 'Cytotoxic T-lymphocyte antigen (CTLA4), Immunoglobulin (Ig)', 'Ig and/or Junction Region', respectively = (1) missing baseline immunogenicity measurement and positive analytical laboratory reported immunogenicity response post-baseline (2) negative baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline (3) positive baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline with titer value strictly greater than the baseline titer value. Assessment based on assay cutpoint value. Serum samples were collected prior to study medication at Week 0 (Day 1), Week 8 (Day 57), and Week 16 (Day 113) in the short term period. Participants who early discontinued from the study or complete and did not switch to commercial abatacept had a serum sample collected on final visit or early termination visit, 28, 84 and 168 days after the last dose.

Full Information

NCT ID

NCT01835470

First Posted

April 17, 2013

Last Updated

February 24, 2021

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01835470

Brief Title

Efficacy, Safety, Pharmacokinetics and Immunogenicity Study of Abatacept Administered Intravenously to Treat Active Polyarticular-course Juvenile Idiopathic Arthritis in Japan

Official Title

A Phase III, Multicenter, Open-Label Study to Assess Efficacy, Safety, Pharmacokinetics and Immunogenicity of Abatacept Administered Intravenously in Japanese Children and Adolescents With Active Juvenile Idiopathic Arthritis Who Have a History of an Inadequate Response or Intolerance to Methotrexate or Biologics

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

August 9, 2013 (Actual)

Primary Completion Date

November 24, 2015 (Actual)

Study Completion Date

July 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to assess the efficacy of Abatacept after intravenous administration in Japanese children and adolescents with active juvenile idiopathic arthritis who have a history of an inadequate response or intolerance to Methotrexate or biologics

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Juvenile Idiopathic Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Abatacept

Arm Type

Experimental

Arm Description

Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study

Intervention Type

Drug

Intervention Name(s)

Abatacept

Other Intervention Name(s)

BMS-188667, ONO-4164

Primary Outcome Measure Information:

Title

Percentage of Participants Experiencing a American College of Rheumatology (ACR) Pediatric 30 Response at Week 16

Description

American College of Rheumatology (ACR) pediatric (PED) 30 response was defined as '≥30% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. JIA core set variables defined as the number of active joints, number of joints with Limit of Motion (LOM), physician's global assessment of disease severity, patient global assessment of overall well being, parent assessment of physical function, and acute phase reactant value. A non-responder imputation was applied.

Time Frame

Week 16 (Day 113)

Secondary Outcome Measure Information:

Title

Percentage of Participants Experiencing a American College of Rheumatology Pediatric 50, 70, 90 Response or Inactive Disease at Week 16

Description

ACR PED 50 response is defined as '≥50% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 70 response is defined as '≥70% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 90 response is defined as '≥90% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Inactive disease status is defined as no active joints, physician's global assessment of disease severity equal or less than 10mm and C-reactive protein (CRP) within normal limits (0.3 mg/dL). A non-responder imputation is applied. mm=millimeter; mg/dL=milligrams/deciliter

Time Frame

Week 16 (Day 113)

Title

Median Percentage of Improvement From Baseline in Physical Function as Assessed by the Childhood Health Assessment Questionnaire (CHAQ) Disability Index at Week 16

Description

Physical function was evaluated using the disability section of the Childhood Health Assessment Questionnaire (CHAQ). The questionnaire was derived from the adult HAQ. The disability section assessed physical functions in 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities. The questions were evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 =unable to do. Higher scores indicate greater dysfunction. A disability index was calculated as the mean of the 8 functional scales. The percentage of Improvement from baseline was calculated using the following equation: (Baseline value - Post-baseline value) / Baseline value x 100.

Time Frame

Week 16 (Day 113)

Title

Number of Participants With Death, Serious Adverse Events (SAEs), Drug-Related SAEs, Discontinuation Due to Drug-Related SAEs, Drug-Related Adverse Events (AEs), and Discontinuation Due to Drug-Related AEs During the Short Term Period

Description

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. SAEs also include hospitalizations for elective surgical procedures. Drug-related=related or missing relationship to study drug. Data includes all events from the date of the first dose of the study drug up to 56 days post the last dose of the study drug in the short-term period or start of the long-term period, whichever occurred first.

Time Frame

Day 1 up to 56 days post Week 16 (Day 113); approximately 6 months

Title

Maximum Observed Concentration (Cmax) of Abatacept During the Short Term Period

Description

Cmax was obtained from the serum concentration versus time data after intravenous administration of abatacept. Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

Time Frame

9 time points up to Week 16 (Day 113)

Title

Trough Observed Concentration (Ctrough) of Abatacept During the Short Term Period

Description

Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

Time Frame

9 time points up to Week 16 (Day 113)

Title

Number of Participants With Positive Immunogenicity During the Short Term Period

Description

A positive immunogenicity response for 'Cytotoxic T-lymphocyte antigen (CTLA4), Immunoglobulin (Ig)', 'Ig and/or Junction Region', respectively = (1) missing baseline immunogenicity measurement and positive analytical laboratory reported immunogenicity response post-baseline (2) negative baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline (3) positive baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline with titer value strictly greater than the baseline titer value. Assessment based on assay cutpoint value. Serum samples were collected prior to study medication at Week 0 (Day 1), Week 8 (Day 57), and Week 16 (Day 113) in the short term period. Participants who early discontinued from the study or complete and did not switch to commercial abatacept had a serum sample collected on final visit or early termination visit, 28, 84 and 168 days after the last dose.

Time Frame

Day 1 up to Week 16 (Day 113)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Subjects who have a history of an inadequate therapeutic response or intolerance in the opinion of the examining physician to at least one biologics or Methotrexate (MTX). Diagnosis of Juvenile Idiopathic Arthritis (JIA) by International League of Associations for Rheumatology (ILAR) criteria as oligoarticular, polyarticular Rheumatoid Factor (RF+), polyarticular (RF-), or systemic with a polyarticular-course. Men and women, ages 4 to 17 years, inclusive at enrollment. Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease as defined by: ≥2 active joints (e.g. presence of swelling, or if no swelling is present, limitation of motion (LOM) accompanied by pain, tenderness, or both) at screening and at Week 0 (Day 1). ≥2 joints with LOM at screening and at Week 0 (Day 1). Exclusion Criteria: Systemic onset JIA with any of the following manifestations within the last 6 months prior to enrollment: intermittent fever due to JIA, rheumatoid rash, hepatosplenomegaly, pleuritis, pericarditis, or macrophage activation syndrome. Presence of any other rheumatic disease or major chronic infectious/inflammatory/immunologic disease (e.g. inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, hypogammaglobulinemia, or systemic lupus erythematosus, etc.)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Local Institution

City

Oobu-shi

State/Province

Aichi

ZIP/Postal Code

4748710

Country

Japan

Facility Name

Local Institution

City

Sapporo-shi

State/Province

Hokkaido

ZIP/Postal Code

0048618

Country

Japan

Facility Name

Local Institution

City

Sapporo-shi

State/Province

Hokkaido

ZIP/Postal Code

0608648

Country

Japan

Facility Name

Local Institution

City

Kobe

State/Province

Hyogo

ZIP/Postal Code

6500047

Country

Japan

Facility Name

Local Institution

City

Kagoshima-shi

State/Province

Kagoshima

ZIP/Postal Code

8908520

Country

Japan

Facility Name

Local Institution

City

Yokohama-shi

State/Province

Kanagawa

ZIP/Postal Code

2328555

Country

Japan

Facility Name

Local Institution

City

Yokohama-shi

State/Province

Kanagawa

ZIP/Postal Code

2360004

Country

Japan

Facility Name

Local Institution

City

Sendai-shi

State/Province

Miyagi

ZIP/Postal Code

9893126

Country

Japan

Facility Name

Local Institution

City

Niigata-shi

State/Province

Niigata

ZIP/Postal Code

9518520

Country

Japan

Facility Name

Local Institution

City

Nakagami-gun

State/Province

Okinawa

ZIP/Postal Code

9030215

Country

Japan

Facility Name

Local Institution

City

Takatsuki-shi

State/Province

Osaka

ZIP/Postal Code

5698686

Country

Japan

Facility Name

Local Institution

City

Bunkyo-ku

State/Province

Tokyo

ZIP/Postal Code

1138603

Country

Japan

Facility Name

Local Institution

City

Shinjuku-ku

State/Province

Tokyo

ZIP/Postal Code

1620054

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

31039807

Citation

Hara R, Umebayashi H, Takei S, Okamoto N, Iwata N, Yamasaki Y, Nakagishi Y, Kizawa T, Kobayashi I, Imagawa T, Kinjo N, Amano N, Takahashi Y, Mori M, Itoh Y, Yokota S. Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study. Pediatr Rheumatol Online J. 2019 Apr 30;17(1):17. doi: 10.1186/s12969-019-0319-4.

Results Reference

derived

Links:

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

BMS Clinical Trial Information

URL

https://www.bmsstudyconnect.com/s/US/English/USenHome

Description

BMS Clinical Trial Patient Recruiting

URL

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

Description

FDA Safety Alerts and Recalls

Juvenile Idiopathic Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial