Safety and Efficacy of Adalimumab in Patients With Active Ankylosing Spondylitis

This study has been completed.
Sponsor:
Information provided by:
Abbott
ClinicalTrials.gov Identifier:
NCT00195819
First received: September 16, 2005
Last updated: June 24, 2011
Last verified: June 2011
  Purpose

The purpose of the study is to assess the safety and clinical efficacy of adalimumab in subjects with active ankylosing spondylitis


Condition Intervention Phase
Ankylosing Spondylitis
Biological: adalimumab (D2E7)
Biological: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS 20 responders - improvement of >=20% and absolute improvement of >=10 units from Baseline in a visual analog scale (VAS) 0 [no disease activity]-100 [high disease activity]) for >=3 of 4 domains; Patient's Global Assessment of disease activity VAS; (0[none]-100 [severe]), Total Back Pain VAS; (0 [no pain]-100 [severe]), BAth Ankylosing Spondylitis Functional Index (BASFI) VAS (0 [easy ]-100[impossible]); and Inflammation VAS; (1 [no pain] to 10 [severe pain]) and absence of deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale.

  • Mean Change in the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Compared Against a Historical Control Group (Outcomes in Ankylosing Spondylitis International Study [OASIS]) Using the ANCOVA Model Adjusting for Baseline mSASSS Score [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
    Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 [no change] to 72 [progression]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.


Secondary Outcome Measures:
  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) 20 - Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    ASAS 20 responders - improvement of >=20% and absolute improvement of >=10 units from Baseline in a visual analog scale (VAS) 0 [no disease activity]-100 [high disease activity]) for >=3 of 4 domains; Patient's Global Assessment of disease activity VAS; (0[none]-100 [severe]), Total Back Pain VAS; (0 [no pain]-100 [severe]), BASFI VAS (0 [easy ]-100[impossible]); and Inflammation VAS; (1 [no pain] to 10 [severe pain]) and absence of deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured by Assessments in Ankylosing Spondylitis (ASAS) ASAS 50 Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    ASAS 50 responders - improvement of >=50% and absolute improvement of >=20 units (0-100) from Baseline in visual analog scale (VAS) for >=3 of the 4 domains; Patient's Global Assessment of disease activity; (0[none]-100[severe]) VAS scale; Total Back Pain VAS; (0 [no pain]-100 [severe]); BASFI VAS; (0 [easy ]-100[impossible]) and Inflammation VAS; (1 [no pain] to 10 [severe pain]). In addition, absence of deterioration in the potential remaining domain. Applied to each scale and not overall global scale.

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Assessments of Ankylosing Spondylitis (ASAS) ASAS 70 Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    ASAS 70 responders - improvement of >=70% and absolute improvement of >=30 units (0-100) from Baseline in visual analog scale (VAS) for >=3 of the 4 domains; Patient's Global Assessment of disease activity VAS; (0[none]-100[severe]) Total Back Pain VAS; (0 [no pain]-100 [severe]); BASFI VAS; (0 [easy ]-100[impossible]) and Inflammation VAS; 1 [no pain] to 10 [severe pain]). In addition, absence of deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale.

  • Mean Change in Patient's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Evaluation of the effect of adalimumab 40 mg every other week (eow) on patient's global assessment of disease activity. The patient was to assess his/her disease activity in the past week using a visual analog scale (VAS) on a scale of 0 to 100 mm with no activity being indicated by 0 and severe activity by 100.

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Patient's Global Assessment of Disease Activity (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The patient assesses his/her disease activity for the past week using a Patient Global Assessment of Disease on visual analog scale (VAS) with 0 being none and 100 being severe.

  • Mean Change in the Bath Ankylosing Spondylitis Functional Index (BASFI) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, 244, and 260 ] [ Designated as safety issue: No ]
    BASFI consist of a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The BASFI score was derived based on the average of questions 1 through 10. The first 8 questions considered activities related to functional anatomy and the final 2 questions assessed the subject's ability to cope with everyday life over the last week. A 10 cm visual analog scale (VAS) was used to answer the questions and the mean of the ten scales gave the BASFI score a value between 0 (easy) and 10 (impossible).

  • BASFI (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    BASFI consisted of 10 Visual Analog Scale (VAS) questions with a response ranging from 0 (easy) to 100 (impossible). The BASFI score was derived based on the average of questions 1 through 10. A responder is a subject who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

  • Mean Change in Total Back Pain Visual Analog Scale (VAS) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Evaluation of the effect of 40 mg every other week (eow) adalimumab on Total Back Pain VAS. The subject was to assess his/her disease activity in the past week using a total spine VAS on a scale 0 (no pain) to 100 (severe pain).

  • Total Back Pain (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 128, 152, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    A responder is a subject who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

  • Mean Change in Inflammation (Mean of BASDAI Questions 5 and 6) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The inflammation score is the mean of the two morning stiffness-related BASDAI visual analog scale (VAS) scores (items 5 and 6 of the BASDAI) of 0 (none) to 10 (very severe). A decrease in inflammation represents improvement.

  • Inflammation (Individual Component of ASAS 20) (Mean of BASDAI Questions 5 and 6) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    A responder is a subject who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline in inflammation (mean of the BASDAI questions 5 and 6 on scale of 0 [none] to 10 [very severe].

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 20 Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

    The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 100(very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 (none) to 10 (very severe). Improvement in BASDAI by 20% was assessed. BASDAI Scoring:

    1. Measure each item of the BASDAI in centimeters (out of a total of 10)
    2. BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

    The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 100 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 50% was assessed. BASDAI Scoring:

    1. Measure each item of the BASDAI in centimeters (out of a total of 10)
    2. BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

  • Number of Subjects With a Reduction of Signs and Symptoms as Measured in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 70 Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

    The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 100 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 70% was assessed. BASDAI Scoring:

    1. Measure each item of the BASDAI in centimeters (out of a total of 10)
    2. BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

  • Mean Change in BASDAI in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 100 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 (none) to 10 (severe). A decrease in BASDAI represents improvement. BASDAI Scoring: 1) Measure each item of the BASDAI in centimeters (out of a total of 10) 2) BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

  • Mean Change in C-Reactive Protein (CRP) (mg/dL) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Evaluation of the mean changes in CRP in subjects with adalimumab exposure from Baseline through 5 years. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation via the use of an ultrasensitive assay. A decrease in the level of CRP indicate reduction in inflammation. A decrease in CRP indicates improvement.

  • Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Assessments of Ankylosing Spondylitis (ASAS) 40 - Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244 and 260 ] [ Designated as safety issue: No ]
    ASAS 40 responder: improvement of >= 40% and absolute improvement of >= 20 units (on a scale of 0 to 100) in >= 3 of the 4 domains: Patient global assessment (VAS score [0-100 scale]); Pain (Total Back Pain VAS score 0-100 scale); Function (BASFI score 0-100 scale); Inflammation (the mean of the two morning stiffness-related BASDAI VAS scores (i.e. the average of items 5 and 6 of the BASDAI. Applied to each scale. In addition, absence of deterioration in the potential remaining domain, where deterioration is defined as a net worsening of > 0 units (on a scale of 0 to 100).

  • Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Assessments of Ankylosing Spondylitis Ankylosing Spondylitis (ASAS) 5/6 in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 16, 20, 24, 30, 36, 42, 48, 52, 64, 76, 88, 104, 116, 128, 140, 156, 168, 180, 192, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

    The change in ASAS 5/6 was evaluated for the effect of adalimumab on structural damage.

    ASAS 5/6 criteria is the 20% improvement in 5 out of 6 domains (physical function [BASFI], Total Back Pain, Patient's Global Assessment of Disease Activity, Inflammation [mean of Questions 5 and 6 of the BASDAI], spinal mobility [BASMI], and acute phase reactants [CRP]).


  • Number of Subjects With a Disease Controlling Clinical Response From Adalimumab as Measured in Partial Remission Response in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Evaluation of the mean changes in BASDAI in subjects with adalimumab exposure from Baseline through 5 years for the effect of adalimumab on structural damage. Partial remission was calculated as follows: A value below 20 on a 0 - 100-point scale in each of the four domains of the ASAS (Patient's Global Assessment of Disease Activity, Pain, Function and Inflammation). Partial remission is also regarded as a low disease activity state.

  • Mean Change in the Bath Ankylosing Spondylitis Metrology Index (BASMI) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance. BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement. The results for cervical rotation and lumbar side flexion are the means of the left and right measurements. Scoring range 0-10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS.

  • Mean Change in Edmonton Ankylosing Spondylitis Metrology Index (EDASMI) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The EDASMI is a composite spinal mobility index comprised of 4 measures: 1) cervical rotation, 2) lumbar side flexion, 3) chest expansion, and 4) hip internal rotation spread. A grade of 0-4 scoring system was developed for each of the measures. The sum of 4 items (range 0 to 16) provide the EDASMI score. Decrease in EDASMI represents improvement. All EDASMI measures were done with a simple tape measure and recorded in centimeters (cm) by a rheumatologist and a clinician nurse.

  • Mean Change in Chest Expansion (CE) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52,104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

    The patient is in a sitting position on the examination table with the hands on the hips. A pen mark is made at the xiphisternum and a tape measure placed around the circumference of the patient's chest at this level. The patient is asked to take a deep breath and to exhale as completely as possible while looking directly ahead. The measurement (in cm) is noted. The patient is asked to inhale as deeply as possible and the measurement (in cm) is noted. The difference in the 2 measurement points (in cm) constitutes the value for CE.

    An increase in chest expansion represents improvement


  • Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 (no tenderness) to 13 (severe tenderness).

  • Mean Change in the Bath Ankylosing Spondylitis Global Index (BAS-G) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    BAS-G consisted of two questions that asked the subject to indicate, on a 10 cm VAS, the effect the disease had on their well being over 1) last week, and 2) last 6 months. BAS-G was measured by two VAS scores (0 to 100 mm) to reflect the effect of Ankylosing Spondylitis on subject's well-being over the past week and over the last 6 months, respectively. The average of these two scores was reported. The mean of the two scores give a BAS-G score of 0-10.

  • Mean Change in Swollen Joint Count for 44 Joints (44 SJC) in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    Change from Baseline in the swollen joint index. An assessment of 44 joints for SJC done by physical examination. Joint swelling was classified as present ("1"), absent ("0") or injected/replaced ("9"). The joints assessed were: Sternoclavicular, Acromioclavicular, Shoulder, Elbow, Wrist, Metacarpophalangeal (1-5), Thumb interphalangeal, Proximal interphalangeal (2-5, Knee, Ankle, and Metatarsophalangeal (1-5).

  • Mean Change From Baseline in the Tender Joint Count for 46 Joints (TJC 46) in Subjects With Adalimumab Exposure Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    Assessment of 46 joints for TJC was done by physical examination. Joint tenderness was classified as present ("1"), absent ("0") or injected/replaced ("9"). The joints assessed were: Sternoclavicular, Acromioclavicular, Shoulder, Elbow, Wrist, Metacarpophalangeal (1-5), Thumb interphalangeal, Proximal interphalangeal (2-5, Knee, Ankle, and Metatarsophalangeal (1-5).

  • Mean Change in Physician's Global Assessment of Disease Activity in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The physician will globally assess the subject's current disease state using a VAS scale with 0 being very good and 100 being very bad.

  • Mean Change in Nocturnal Pain in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    The subject was to assess his/her nocturnal pain intensity for the past week using a Nocturnal Pain Visual Analog Scale (Nocturnal Pain VAS). The range was 0 to 100 mm with no pain being indicated by 0 and worse possible pain by 100.

  • Mean Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale in Subjects With Adalimumab Exposure Through Week 260 [ Time Frame: Baseline and at Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue scale: overall score of 13 general questions divided into four primary Quality of Life (QoL) domains: 1) Physical Well-Being, 2) Social/Family Well-Being, 3) Emotional Well-Being, and 4) Functional Well-Being. For each question subject rates his/her condition for the past week on a 5-point scale ranging from 0 (not at all) to 4 (very much). The score ranges from 0 (highest level of fatigue) to 52 with 52 being the lowest level of fatigue.

  • Mean Change in the SF-36 Health Survey Index Physical Component Summary [PCS] Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    Change from Baseline in the SF-36 Health Survey Index completed by Subject to help subject keep track of how he/she was feeling and how well he/she was able to do usual activities. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicate improvement.

  • Number of Subjects With SF-36 Physical Component Summary (PCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]

    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0(no functioning)to 100 (highest level of functioning).

    Responders were subjects with MCID > 3 points. Minimal clinically important difference (MCID) for PCS was determined by a >= 3.0 point increase during exposure to adalimumab.


  • Mean Change in the SF-36 Health Survey Index Mental Component Summary [MCS] Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). Change from Baseline in the SF-36 Health Survey Index was completed by Subject. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicated improvement.

  • Number of Subjects With SF-36 Mental Component Summary (MCS) of Minimal Clinically Important Difference (MCID) Response Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey completed by Subject, evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). Responders are subjects with MCID > 3 points. Minimal clinically important difference (MCID) for PCS was determined by a >= 3.0 point increase during exposure to adalimumab.

  • Mean Change in Health Utilities Index-3 (HUI-3) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 24, 52, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    Change from baseline in Health Utility Index Mark 3 (HUI-3) was reported. The HUI-3 is a generic approach to the measurement of health status and assessment of HRQL. The HUI-3 was comprised of two complementary components. The first component was a multi-attribute health status classification system that was used to describe health status. The second component was a multi-attribute utility function that was used to value health status as measured within the corresponding multi-attribute health status classification system. An increase in the HUI-3 score represents improvement.

  • Mean Change in the Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) in Subjects Through Week 260 of Adalimumab Exposure [ Time Frame: Baseline and at Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    ASQoL determined subject's quality of life and is comprised of 18 questions (yes or no) to be completed by the subject. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score or index. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement.

  • Number of Subjects With Ankylosing Spondylitis Quality of Life Questionaire (ASQoL) MCID Response (MCID <= -1.8 Points) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]
    ASQoL determined subject's quality of life comprised of 18 questions to be completed by the subject. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement. Responders are subjects with MCID <= -1.8 points. MCID was determined by a >= 1.8 score decrease during exposure to adalimumab.

  • Number of Subjects Achieving the Patient Acceptable Symptoms State Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 232, and 260 ] [ Designated as safety issue: No ]

    Completed by subject at each visit. The MCIS was a patient reported outcome where the subjects were expected to respond (yes/no) to the following question:

    Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory? An increase in PASS indicates improvement.

    During earlier weeks of the study PASS was measured/reported as minimal clinically important state (MCIS).


  • Mean Change From Baseline in Serum Matrix Metalloproteinase-3 (MMP-3) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Cartilage and bone degradation were assessed by evaluating changes in MMP-3. A decrease in MMP-3 represents improvement.

  • Mean Change From Baseline in Urine Type II Collagen C Telopeptide (CTX-II) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Cartilage and bone degradation were assessed by evaluating changes in CTX-II. A decrease in CTX-II represents improvement.

  • Mean Change From Baseline in Serum Type I Collagen N-telopeptide (NTx) in Subjects Treated With Any Dose of Adalimumab Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]
    Cartilage degradation and bone resorption were assessed by evaluating changes in NTx. A decrease in NTx represents improvement.

  • Mean Change in Spinal Spondyloarthritis Research Consortium of Canada (S.P.A.R.C.C.) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score at Weeks 12 and 52 of Adalimumab Exposure [ Time Frame: Week 12 and Week 52 ] [ Designated as safety issue: No ]
    The S.P.A.R.C.C. MRI index is a tool for scoring inflammation and structural damage in both the spine and sacroiliac (SI) joints. The spinal SPARCC index score consists of 3 subscales (edema, intense edema, and deep edema). Edema was defined as the presence of increased STIR signal in each of 4 Discovertebral unit (DVU) quadrants and was assigned a score (0 = normal signal, 1 = increased signal). The scoring of edema was repeated for each of 3 consecutive sagittal slices with a maximum score of 12 per DVU (range for edema, 0-72). The total spinal SPARCC index score is 0 to 108.

  • Mean Change in Sacroiliac (SI) Spondyloarthritis Research Consortium of Canada (S.P.A.R.C.C.) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score at Weeks 12 and 52 of Adalimumab Exposure [ Time Frame: Weeks 12 and 52 ] [ Designated as safety issue: No ]
    The S.P.A.R.C.C. MRI index is a tool for scoring inflammation and structural damage in both the spine and sacroiliac (SI) joints. The spinal SPARCC index score consists of 3 subscales (edema, intense edema, and deep edema). Edema was defined as the presence of increased STIR signal in each of 4 Discovertebral unit (DVU) quadrants and was assigned a score (0 = normal signal, 1 = increased signal). The scoring of edema was repeated for each of 3 consecutive sagittal slices with a maximum score of 12 per DVU (range for edema, 0-72). The total spinal SPARCC index score is 0 to 108.


Enrollment: 82
Study Start Date: December 2003
Study Completion Date: June 2009
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab Biological: adalimumab (D2E7)
Adalimumab 40 mg every other week (eow)
Other Names:
  • ABT-D2E7
  • adalimumab
  • Humira
Placebo Comparator: Placebo Biological: placebo
Placebo every other week (eow)
Other Name: placebo

  Eligibility

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

Inclusion Criteria:

  • Subject was age 18 or older and in relatively good health (Investigator discretion) with a recent stable medical history.
  • Subject met the definition of AS based on the Modified New York Criteria.
  • Subject had an inadequate response to or intolerance to one or more NSAIDs as defined by the Investigator

Exclusion Criteria:

  • Subject had previously received anti-TNF therapy.
  • Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
  • Female subject who is pregnant or breast-feeding or considering becoming pregnant
  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: NCT00195819

Locations
Canada, Alberta
Site Ref # / Investigator 74
Calgary, Alberta, Canada, T2N 4N1
Site Ref # / Investigator 70
Edmonton, Alberta, Canada, T6G 2S2
Canada, British Columbia
Site Ref # / Investigator 79
Vancouver, British Columbia, Canada, V5Z 1L7
Canada, Manitoba
Site Ref # / Investigator 64
Winnipeg, Manitoba, Canada, R3N OK6
Canada, Newfoundland and Labrador
Site Ref # / Investigator 78
St. John's, Newfoundland and Labrador, Canada, A1C 5B8
Canada, Ontario
Site Ref # / Investigator 62
Toronto, Ontario, Canada, M5T 2S8
Site Ref # / Investigator 63
Toronto, Ontario, Canada, M5L 3L9
Site Ref # / Investigator 75
Toronto, Ontario, Canada, M4N 3M5
Canada, Saskatchewan
Site Ref # / Investigator 77
Saskatoon, Saskatchewan, Canada, S7K 0H6
Sponsors and Collaborators
Abbott
  More Information

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Beverly Paperiello, Director of Clinical Project Management, Abbott
ClinicalTrials.gov Identifier: NCT00195819     History of Changes
Other Study ID Numbers: M03-606
Study First Received: September 16, 2005
Results First Received: December 17, 2009
Last Updated: June 24, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Abbott:
ankylosing spondylitis
adalimumab

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

ClinicalTrials.gov processed this record on October 02, 2014