A Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis
Primary Purpose
Enthesitis Related Arthritis (ERA)
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
adalimumab
placebo for adalimumab
Sponsored by
About this trial
This is an interventional treatment trial for Enthesitis Related Arthritis (ERA) focused on measuring inflammatory back pain, ankylosing spondylitis, sacroiliitis, Juvenile Idiopathic Arthritis, enthesitis, arthritis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Enthesitis Related Arthritis (ERA) as defined by International League of Associations for Rheumatology (ILAR);
- Disease activity defined as at least 3 active joints and evidence of enthesitis in at least one location;
- Inadequate response or intolerance to at least one nonsteroidal anti-inflammatory drug and at least one disease modifying anti-rheumatic drug, either sulfasalazine or methotrexate.
Exclusion Criteria:
- Any ILAR Juvenile Idiopathic Arthritis (JIA) subtype other than ERA;
- Psoriasis or a history of psoriasis in the patient or first-degree relative;
- Presence of Immunoglobulin M (IgM) rheumatoid factor;
- Presence of systemic JIA;
- History of inflammatory bowel disease;
- previous biologic therapy including anti-tumor necrosis factor (anti-TNF) therapy with a potential impact on pediatric ERA;
- Infection(s) requiring treatment with IV anti-infectives within 30 days prior to Baseline or oral anti-infectives within 14 days prior to Baseline.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Double-blind Placebo EOW
Double-blind Adalimumab EOW
Open-label Adalimumab EOW
Arm Description
Placebo for adalimumab every other week (eow) for 12 weeks.
Adalimumab (body surface area dosing 24 mg/m^2 up to a maximum of 40 mg) every other week (eow) for 12 weeks.
Adalimumab (body surface area dosing 24 mg/m^2 up to a maximum of 40 mg) every other week (eow) for up to 192 weeks.
Outcomes
Primary Outcome Measures
Percent Change in Number of Active Joints With Arthritis From Baseline to Week 12
A joint assessment was recorded at all study visits to assess the number of active joints. A total of 72 joints were assessed for swelling not due to deformity or joints with loss of motion (LOM) plus pain and/or tenderness. Total possible scores ranges from 0 (no active joints) to 72 (all active joints). Baseline is defined as the last nonmissing value prior to the first dose of study drug. Last Observation Carried Forward (LOCF) was used for missing data.
Secondary Outcome Measures
Number of Sites of Enthesitis: Change From Baseline to Week 12
The presence of enthesitis was assessed by pressure at 35 anatomical locations. Enthesitis was classifed as either present or absent. Scores range from 0 to 35, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Tender Joint Count (TJC72): Change From Baseline to Week 12
Seventy-two joints were assessed by pressure on physical examination. Joint tenderness was classified as either present or absent. Scores range from 0 to 72, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Swollen Joint Count (SJC68): Change From Baseline to Week 12
Sixty-eight joints were assessed by physical examination. Joint swelling was classified as present or absent. Scores range from 0 to 68, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 30% Response (ACR Pedi30)
The ACR Pedi30 response is defined as ≥30% improvement in at least 3 of 6 juvenile rheumatoid arthritis (JRA) core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. Non-responder imputation (NRI) was used for missing data.
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 50% Response (ACR Pedi50)
The ACR Pedi50 response is defined as ≥50% improvement in at least 3 of 6 JRA core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. NRI was used.
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 70% Response (ACR Pedi70)
The ACR Pedi70 response is defined as ≥70% improvement in at least 3 of 6 JRA core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. Non-responder imputation NRI was used.
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs or TESAE) are defined as any event that began or worsened in severity after the first dose of study drug. The investigator assessed the relationship of each event to the use of study drug as either probably related to study drug, possibly related to study drug, probably not related, or not related to study drug.
For more details on adverse events please see the AE section below.
Full Information
NCT ID
NCT01166282
First Posted
July 19, 2010
Last Updated
July 8, 2021
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01166282
Brief Title
A Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis
Official Title
A Double-blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of adalimumab given subcutaneously every other week (eow) as compared to placebo in pediatric subjects with Enthesitis Related Arthritis (ERA).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Enthesitis Related Arthritis (ERA)
Keywords
inflammatory back pain, ankylosing spondylitis, sacroiliitis, Juvenile Idiopathic Arthritis, enthesitis, arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Double-blind Placebo EOW
Arm Type
Placebo Comparator
Arm Description
Placebo for adalimumab every other week (eow) for 12 weeks.
Arm Title
Double-blind Adalimumab EOW
Arm Type
Experimental
Arm Description
Adalimumab (body surface area dosing 24 mg/m^2 up to a maximum of 40 mg) every other week (eow) for 12 weeks.
Arm Title
Open-label Adalimumab EOW
Arm Type
Experimental
Arm Description
Adalimumab (body surface area dosing 24 mg/m^2 up to a maximum of 40 mg) every other week (eow) for up to 192 weeks.
Intervention Type
Biological
Intervention Name(s)
adalimumab
Other Intervention Name(s)
ABT-D2E7, Humira
Intervention Description
Adalimumab solution for subcutaneous injection.
Intervention Type
Biological
Intervention Name(s)
placebo for adalimumab
Intervention Description
Placebo for adalimumab solution for subcutaneous injection.
Primary Outcome Measure Information:
Title
Percent Change in Number of Active Joints With Arthritis From Baseline to Week 12
Description
A joint assessment was recorded at all study visits to assess the number of active joints. A total of 72 joints were assessed for swelling not due to deformity or joints with loss of motion (LOM) plus pain and/or tenderness. Total possible scores ranges from 0 (no active joints) to 72 (all active joints). Baseline is defined as the last nonmissing value prior to the first dose of study drug. Last Observation Carried Forward (LOCF) was used for missing data.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Number of Sites of Enthesitis: Change From Baseline to Week 12
Description
The presence of enthesitis was assessed by pressure at 35 anatomical locations. Enthesitis was classifed as either present or absent. Scores range from 0 to 35, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Time Frame
Baseline and Week 12
Title
Tender Joint Count (TJC72): Change From Baseline to Week 12
Description
Seventy-two joints were assessed by pressure on physical examination. Joint tenderness was classified as either present or absent. Scores range from 0 to 72, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Time Frame
Baseline and Week 12
Title
Swollen Joint Count (SJC68): Change From Baseline to Week 12
Description
Sixty-eight joints were assessed by physical examination. Joint swelling was classified as present or absent. Scores range from 0 to 68, with higher scores representing higher disease activity. Baseline is defined as the last nonmissing value prior to the first dose of study drug. LOCF was used.
Time Frame
Baseline and Week 12
Title
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 30% Response (ACR Pedi30)
Description
The ACR Pedi30 response is defined as ≥30% improvement in at least 3 of 6 juvenile rheumatoid arthritis (JRA) core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. Non-responder imputation (NRI) was used for missing data.
Time Frame
Baseline and Week 12
Title
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 50% Response (ACR Pedi50)
Description
The ACR Pedi50 response is defined as ≥50% improvement in at least 3 of 6 JRA core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. NRI was used.
Time Frame
Baseline and Week 12
Title
Percentage of Participants Achieving Pediatric American College of Rheumatology Pediatric 70% Response (ACR Pedi70)
Description
The ACR Pedi70 response is defined as ≥70% improvement in at least 3 of 6 JRA core set criteria with no more than 1 of the 6 criteria with >30% worsening. The 6 variables for the JRA core set criteria are Physician's Global Assessment (PGA) of participant's disease activity, Parent's Global Assessment of participant's overall well-being, number of active joints (joints with swelling not due to deformity or joints LOM plus pain and/or tenderness), number of joints with LOM, Childhood Health Assessment Questionnaire (CHAQ), and high sensitivity C-reactive protein (hs CRP). Baseline is the last value prior to the first dose of study drug. Non-responder imputation NRI was used.
Time Frame
Baseline and Week 12
Title
Number of Participants With Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs or TESAE) are defined as any event that began or worsened in severity after the first dose of study drug. The investigator assessed the relationship of each event to the use of study drug as either probably related to study drug, possibly related to study drug, probably not related, or not related to study drug.
For more details on adverse events please see the AE section below.
Time Frame
Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 70 days after the last dose of study drug (up to 212 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Enthesitis Related Arthritis (ERA) as defined by International League of Associations for Rheumatology (ILAR);
Disease activity defined as at least 3 active joints and evidence of enthesitis in at least one location;
Inadequate response or intolerance to at least one nonsteroidal anti-inflammatory drug and at least one disease modifying anti-rheumatic drug, either sulfasalazine or methotrexate.
Exclusion Criteria:
Any ILAR Juvenile Idiopathic Arthritis (JIA) subtype other than ERA;
Psoriasis or a history of psoriasis in the patient or first-degree relative;
Presence of Immunoglobulin M (IgM) rheumatoid factor;
Presence of systemic JIA;
History of inflammatory bowel disease;
previous biologic therapy including anti-tumor necrosis factor (anti-TNF) therapy with a potential impact on pediatric ERA;
Infection(s) requiring treatment with IV anti-infectives within 30 days prior to Baseline or oral anti-infectives within 14 days prior to Baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaclyn Anderson, DO, MS
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26223543
Citation
Burgos-Vargas R, Tse SM, Horneff G, Pangan AL, Kalabic J, Goss S, Unnebrink K, Anderson JK. A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis-Related Arthritis. Arthritis Care Res (Hoboken). 2015 Nov;67(11):1503-12. doi: 10.1002/acr.22657.
Results Reference
result
PubMed Identifier
30054164
Citation
Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.
Results Reference
derived
Links:
URL
http://rxabbvie.com
Description
Related Info.
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A Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis
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