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Study of Adalimumab in Patients With Axial Spondyloarthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00939003
First received: July 10, 2009
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This study will evaluate how well adalimumab works in the short and long term in patients with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.


Condition Intervention Phase
Axial Spondyloarthritis
Biological: Adalimumab
Biological: Placebo
Biological: Open-label 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 Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Axial Spondyloarthritis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale from 0 to 100) in the potential remaining domain:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).


Secondary Outcome Measures:
  • Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    ASAS20 response was defined as improvement of ≥ 20% relative to Baseline and absolute improvement of ≥ 10 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a change for the worse of ≥ 20% and net worsening of ≥ 10 units) in the potential remaining domain:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  • Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.

  • Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life. The SF-36 consists of 36 questions in 8 domains (limitations in physical functioning due to health problems; limitations in usual role because of physical health problems; bodily pain; general health perceptions; vitality; limitations in social functioning because of physical or emotional problems; limitations in usual role due to emotional problems; and general mental health). Two component scores can be summarized: physical and mental; domains 1-4 comprise the physical component summary of the SF-36. A transformed summary score is calculated ranging from 0 to 100 where higher scores indicate a higher level of functioning. A positive change from Baseline score indicates an improvement.

  • Number of Participants Achieving ASAS Partial Remission [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    ASAS partial remission is an absolute score of < 20 units on a 0 to 100 scale for each of the four following domains:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  • Number of Participants Achieving an ASAS5/6 Response [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    ASAS5/6 response is a 20% improvement in five out of the following six domains:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none) to 10 (very severe/2 hours or more duration).
    • Spinal mobility, measured from the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility);
    • C-reactive protein level (lower levels indicate less inflammation).

  • Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Health Assessment Questionnaire modified for spondyloarthropathies (HAQ-S) is a self-reported measure to assess the physical function and health-related quality of life. The Disability Index (DI) of HAQ-S is calculated as the mean of the following 8 category scores (range: 0 [without any difficulty] to 3 [unable to do]): Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Five additional items in the functional status measure were included in the HAQ-S, including carrying heavy packages, sitting for long periods, able to work at a flat topped table, and (if the participant had a driver's license or a car) able to look in the rear view mirror and able to turn head to drive in reverse. The overall score ranges from 0 (no disability) to 3 (three very severe, high-dependency disability). Negative mean changes from Baseline in the overall score indicate improvement.

  • Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    C-reactive protein (CRP) is considered an efficacy variable for the axial spondyloarthritis indication. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response. Higher levels indicate more inflammation.

  • Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    Six consecutive sacroiliac (SI) joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema using SPARCC scoring.

    Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema; the maximum score is 8 per slice and maximum score for 6 SI joint slices is 48.

    Intensity of edema: A score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice. The maximum score is 2 per slice and 12 for 6 slices.

    A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The maximum score per slice is 2 and for 6 slices 12.

    The total maximum score for all SI joints across 6 slices is 72.


  • Change From Baseline in SPARCC MRI Score for the Spine [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    Six discovertebral units (DVU) representing the 6 most abnormal DVUs, and 3 consecutive sagittal slices at each DVU representing the most abnormal slices for that DVU were selected for scoring. Each DVU was divided into 4 quadrants and scored for the presence (1) or absence (0) of edema. The maximum score is 12 per DVU. The maximum score is 72 for 6 DVUs.

    If edema was present in at least 1 quadrant of a DVU slice, it was scored for intensity and depth of the edema representing that slice:

    A score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. The maximum score for intensity per slice is 1, per DVU is 3 and for 6 DVUs is 18.

    A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the surface of the endplate in any quadrant. The maximum score per slice is 1, for a DVU is 3 and for 6 DVUs is 18.

    The total maximum SPARCC score for all 6 DVUs is 108.



Other Outcome Measures:
  • Number of Participants Reporting Adverse Events [ Time Frame: Through Week 12 ] [ Designated as safety issue: Yes ]
    Adverse events were collected at designated study visits for all participants who received at least 1 dose of study drug. The number of participants experiencing any adverse event (serious and non-serious) is summarized.

  • Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3 [ Time Frame: Through Week 12 ] [ Designated as safety issue: Yes ]
    Blood was collected for analysis at designated study visits; hematology and chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher then upper normal limit or lower than lower normal limit) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized.

  • Number of Participants Achieving an ASAS20 Response During the Open-label Period [ Time Frame: Baseline and Weeks 52, 104, and 156 ] [ Designated as safety issue: No ]

    ASAS20 response was defined as improvement of ≥ 20% relative to Baseline and absolute improvement of ≥ 10 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a change for the worse of ≥ 20% and net worsening of ≥ 10 units) in the potential remaining domain:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  • Number of Participants Achieving an ASAS40 Response During the Open-label Period [ Time Frame: Baseline and Weeks 52, 104, and 156 ] [ Designated as safety issue: No ]

    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale of 0 to 100) in the potential remaining domain:

    • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe);
    • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe);
    • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible);
    • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).

  • Number of Participants Achieving a BASDAI50 Response During the Open-label Period [ Time Frame: Baseline and Weeks 52, 104, and 156 ] [ Designated as safety issue: No ]
    The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.


Enrollment: 192
Study Start Date: July 2009
Study Completion Date: August 2013
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab Biological: Adalimumab
40 mg every other week up to Week 12
Other Names:
  • ABT-D2E7
  • Humira
Placebo Comparator: Placebo Biological: Placebo
Placebo every other week up to Week 12
Experimental: Open-label Adalimumab Biological: Open-label Adalimumab
40 mg every other week, Week 12 through Week 156
Other Names:
  • ABT-D2E7
  • Humira

Detailed Description:

This is a Phase 3, placebo-controlled, double-blind randomized study with an open-label phase designed to evaluate the efficacy and safety of adalimumab 40 mg administered every other week in adult patients with active axial spondyloarthritis (SpA) who are not diagnosed with ankylosing spondylitis, psoriasis, or psoriatic arthritis and who have had an inadequate response or intolerance to one or more nonsteroidal anti-inflammatory drugs (NSAIDs) or had a contraindication to NSAIDs. Participants receive adalimumab or placebo for 12 weeks during the double-blind phase of the study. Following the double-blind phase, all remaining participants enter the open-label phase of the study in which they receive open-label adalimumab for up to 144 weeks. Efficacy endpoints include the Assessment of Spondyloarthritis International Society (ASAS) response criteria for patients with SpA. These response criteria were used to determine participants who were responders. ASAS response involves evaluations in the following 4 domains: participant's global assessment of disease activity, pain, function, and inflammation. The patient's global assessment of disease activity score is assessed using a 100 millimeter (mm) visual analog scale (VAS; 0 for no disease activity to 100 for severe disease activity). Pain is represented as a total back pain score and is assessed using a 100 mm VAS (0 for no pain to 100 for most severe pain). Function score is represented as the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI) 100 mm VAS score (average of the ability to perform 10 activities, each scored as 0 for easy to 100 for impossible). Inflammation is determined using the morning stiffness overall level score (0 for none to 10 for very severe) and duration score (0 for 0 hours to 10 for ≥ 2 hours) of the Bath AS Disease Activity Index (BASDAI) (mean of these items #5 and #6 scores). In addition, the BASDAI is used as an efficacy endpoint. The BASDAI is used by the participant to assess his/her disease activity. Using VAS scales, the participant answers 6 questions pertaining to symptoms experienced over the past week. For 5 questions (levels of: fatigue/tiredness; AS neck, back, or hip pain; pain/swelling; discomfort at areas tender to touch or pressure; and morning stiffness), the response scale is 0 (none) to 10 (very severe). For 1 question (duration of morning stiffness), the response scale is 0 (0 hours) to 10 (≥ 2 or more hours).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with inadequate response to >/= 1 non-steroidal anti-inflammatory drugs (NSAIDs)
  • Chronic back pain with onset < 45 years of age
  • Magnetic resonance imaging (MRI) indicating active sacroiliitis or positive human leukocyte antigen-B27 (HLA-B27) blood test in addition to meeting spondyloarthritis clinical criteria
  • Negative purified protein derivative (PPD) test and chest x-ray performed at Baseline visit must be negative
  • Ability to administer subcutaneous injections
  • General good health otherwise

Exclusion Criteria:

  • Prior anti-tumor necrosis factor (TNF) therapy
  • Psoriasis or psoriatic arthritis
  • Fulfillment of modified New York criteria for ankylosing spondylitis
  • Recent infection requiring treatment
  • Significant medical events or conditions that may put patients at risk for participation
  • Females who are pregnant or breast-feeding or considering becoming pregnant during the study
  • History of cancer, except successfully treated skin cancer
  • Recent history of drug or alcohol abuse
  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: NCT00939003

  Show 38 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Aileen L Pangan, MD AbbVie
  More Information

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00939003     History of Changes
Other Study ID Numbers: M10-791, 2009-010643-14
Study First Received: July 10, 2009
Results First Received: February 2, 2012
Last Updated: September 4, 2014
Health Authority: Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence francaise de securite sanitaire des produits de sante (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Spondylarthritis
Spondylitis
Arthritis
Bone Diseases
Bone Diseases, Infectious
Infection
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014