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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
AbbVie (prior sponsor, Abbott)
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

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

    First Posted
    July 19, 2010
    Last Updated
    July 8, 2021
    Sponsor
    AbbVie (prior sponsor, Abbott)
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    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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