A Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis

Study Overview
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Brief Summary
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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).

Official Title
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A Double-blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis

Conditions
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Enthesitis Related Arthritis (ERA)

Intervention / Treatment
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* Biological: adalimumab
* Biological: placebo for adalimumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double-blind Placebo EOW<br>Placebo for adalimumab every other week (eow) for 12 weeks. | Biological: placebo for adalimumab<br>* Placebo for adalimumab solution for subcutaneous injection.<br>|
| Experimental: Double-blind Adalimumab EOW<br>Adalimumab (body surface area dosing 24 mg/m^2 up to a maximum of 40 mg) every other week (eow) for 12 weeks. | Biological: adalimumab<br>* Adalimumab solution for subcutaneous injection.<br>* Other names: Humira;|
| Experimental: Open-label Adalimumab EOW<br>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. | Biological: adalimumab<br>* Adalimumab solution for subcutaneous injection.<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | Baseline and Week 12 | 
| 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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory back pain, ankylosing spondylitis, sacroiliitis, Juvenile Idiopathic Arthritis, enthesitis, arthritis