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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01166282
First received: July 19, 2010
Last updated: June 24, 2016
Last verified: June 2016
  Purpose
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).

Condition Intervention Phase
Enthesitis Related Arthritis (ERA)
Biological: adalimumab
Biological: placebo for adalimumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Adalimumab in Pediatric Subjects With Enthesitis Related Arthritis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percent Change in Number of Active Joints With Arthritis From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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) [ 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) ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 46
Study Start Date: September 2010
Study Completion Date: December 2015
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Double-blind Placebo EOW
Placebo for adalimumab every other week (eow) for 12 weeks.
Biological: placebo for adalimumab
Placebo for adalimumab solution for subcutaneous injection.
Experimental: Double-blind Adalimumab EOW
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
Adalimumab solution for subcutaneous injection.
Other Names:
  • ABT-D2E7
  • Humira
Experimental: Open-label Adalimumab EOW
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
Adalimumab solution for subcutaneous injection.
Other Names:
  • ABT-D2E7
  • Humira

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01166282

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Jaclyn Anderson, DO, MS AbbVie
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01166282     History of Changes
Other Study ID Numbers: M11-328  2009-017938-46 
Study First Received: July 19, 2010
Results First Received: May 12, 2016
Last Updated: June 24, 2016
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Canada: Health Canada
Mexico: Ministry of Health
Poland: The Central Register of Clinical Trials
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Sweden: Medical Products Agency
Italy: The Italian Medicines Agency
Germany: Paul-Ehrlich-Institut
Ireland: Irish Medicines Board
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by AbbVie:
inflammatory back pain
ankylosing spondylitis
sacroiliitis
Juvenile Idiopathic Arthritis
enthesitis
arthritis

Additional relevant MeSH terms:
Arthritis
Tendinopathy
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Muscular Diseases
Tendon Injuries
Wounds and Injuries
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 28, 2016