Study Evaluating Etanercept for the Treatment of Active, Severe, and Advanced Axial Ankylosing Spondylitis

This study has been completed.
Sponsor:
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00420238
First received: January 8, 2007
Last updated: June 24, 2010
Last verified: June 2010
  Purpose

Evaluation of the efficacy and safety of etanercept (Enbrel) in patients with active, severe and advanced ankylosing spondylitis.


Condition Intervention Phase
Ankylosing Spondylitis
Drug: Etanercept (Enbrel)
Other: Placebo
Phase 4

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 Multicentre, Double-Blind, Placebo-Controlled, Randomised Study of Etanercept in the Treatment of Adult Patients With Active, Severe, and Advanced Axial Ankylosing Spondylitis

Resource links provided by NLM:


Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Primary Outcome Measures:
  • Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Disease Activities Index (BASDAI) Between Randomization and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASDAI subject asessment of discomfort, pain and fatigue measured using a 100 millimeter Visual Analog Scale; range: 0=none to 100=very severe. Normalized net incremental area under the curve (AUC) = area between baseline and the BASDAI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.


Secondary Outcome Measures:
  • Percent of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASDAI subject assessment of discomfort, pain and fatigue was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=very severe. BASDAI 50 response defined as at least a 50 percent (%) improvement (decrease) from baseline to observation (last observation carried forward) in the BASDAI. Baseline score minus score at observation divided by Baseline score * 100 = >=50%.

  • Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 20 at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function,and inflammation. ASAS 20 = 20% improvement (versus baseline) and an absolute change (net improvement) ≥ 10 millimeters (mm) on a 0-100 mm scale (100=high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.

  • Percent of Subjects Acheiving Assessment Ankylosing Spondylitis (ASAS) 20 at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, and inflammation. ASAS 20 = 20% improvement (versus baseline) and an absolute change (net improvement) ≥ 10 units (millimeters) on a 0-100 scale (100=high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.

  • Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 50 at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (versus baseline) and an absolute (net) change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.

  • Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 50 at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (vs. baseline) and an absolute (net) change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.

  • Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 70 at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.

  • Percent of Subjects Achieiving Assessment Ankylosing Spondylitis (ASAS) 70 at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.

  • Percent of Subjects Achieving Partial Remission at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Partial remission defined as a score of <20 millimeters (mm) on a scale of 0 to 100 mm in each of 4 domains: Visual Analog Scale (VAS) patient global assessment, VAS pain score (Total Back Pain), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and Bath Ankylosing Spondylitis Disease Activities Index (BASDAI)-mean of two morning stiffness-related VAS scores. A negative score indicates an improvement in disease activity and a positive score indicates worsening.

  • Percent of Subjects Achieving Partial Remission at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Partial remission defined as a score of <20 millimeters (mm) on a scale of 0 to 100 mm in each of 4 domains: Visual Analog Scale (VAS) patient global assessment, VAS pain score (Total Back Pain), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and Bath Ankylosing Spondylitis Disease Activities Index (BASDAI)-mean of two morning stiffness-related VAS scores. A negative score indicates an improvement in disease activity and a positive score indicates worsening.

  • Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment (PGA) Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    PGA was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = very good to 100 = very bad. Normalized net incremental area under the curve (AUC)=area between baseline and the Patient Global Asessment curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Patient Global Assessment Visual Analog Scale (VAS) at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Patient global assessment of all the ways ankylosing spondylitis affected them in the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range 0=very good to 100=very bad.

  • Change From Baseline in Patient Global Assessment at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Patient global assessment of all the ways ankylosing spondylitis affected them in the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range 0=very good to 100=very bad.

  • Normalized Net Incremental Area Under the Curve (AUC) for Physician Global Assessment (PGA) Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    PGA was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = very good to 100 = very bad. Normalized net incremental area under the curve (AUC) = area between baseline and the Physician Global Assessment curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Physician Global Assessment Visual Analog Scale at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Physician global assessment of all the ways ankylosing spondylitis has affected patient during the last 48 hours. 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=very good to 100=very bad.

  • Change From Baseline in Physician Global Assessment at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Physician global assessment of all the ways ankylosing spondylitis has affected patient during the last 48 hours. 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=very good to 100=very bad.

  • Normalized Net Incremental Area Under the Curve (AUC) for Nocturnal Back Pain Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Nocturnal back pain was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0 = none to 100 = extreme. Normalized net incremental area under the curve (AUC) = area between baseline and the Nocturnal Back Pain curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Nocturnal Back Pain at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject assessment of nocturnal back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.

  • Change From Baseline in Nocturnal Back Pain at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subject assessment of nocturnal back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.

  • Normalized Net Incremental Area Under the Curve (AUC) for Total Back Pain Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Total back pain was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0 = none to 100 = extreme. Normalized net incremental area under the curve (AUC) = area between baseline and the Total Back Pain curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Total Back Pain at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject assessment of total back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.

  • Change From Baseline in Total Back Pain at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subject assessment of total back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=extreme.

  • Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Functional Index (BASFI) Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASFI was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = easy to 100 = impossible. Normalized net incremental area under the curve (AUC) = area between baseline and the BASFI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in ankylosing spondylitis (AS) patients using a 100 millimeter (mm) Visual Analog Scale (VAS) measuring level of ability with activities in the last 48 hours; range: 0=easy to 100=impossible. Higher score = greater limitation.

  • Bath Ankylosing Functional Index (BASFI): Independent Components at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject rating of last 48 hours, 100 millimeter Visual Analog Scale; range 0=easy to 100=impossible: 1)Putting on socks/tights without (w/o) help; 2)Bending forward from waist to pickup pen from floor w/o aid; 3)Reaching to high shelf w/o aid; 4)Getting out of armless dining room chair w/o using hands/other help; 5)Getting up off floor w/o help from lying on back; 6)Standing unsupported 10 minutes w/o discomfort; 7)Climbing 12-15 steps w/o handrail or walking aid; 8)Looking over shoulder w/o turning body; 9) Doing physically demanding activities; 10) Doing full days activities (home or work).

  • Bath Ankylosing Functional Index (BASFI) Independent Components at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subject rating of last 48 hours, 100 mm Visual Analog Scale; range 0=easy to 100=impossible: 1) Putting on socks/tights without (w/o) help; 2) Bending forward from waist to pickup pen from floor w/o aid; 3) Reaching to high shelf w/o aid; 4) Getting out of armless dining room chair w/o using hands/other help; 5) Getting up off floor w/o help from lying on back; 6) Standing unsupported 10 minutes w/o discomfort; 7) Climbing 12-15 steps w/o handrail or walking aid; 8) Looking over shoulder w/o turning body; 9) Doing physically demanding activities; 10) Doing full days activities (home or work).

  • Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in patients with ankylosing spondylitis in the last 48 hours. Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments.

  • Change From Baseline in the Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in patients with ankylosing spondylitis (AS) in the last 48 hours. Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments.

  • Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) Independent Components at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASDAI subject rated components over last 48 hours using 100 mm Visual Analog Scale; components 1-5: range 0=none to 100=very severe; component 6: range:0=0 hours to 100=2 hours or more. 1) Overall level of fatigue/tiredness experienced; 2) Overall level of AS neck,back or hip pain experienced; 3) Overall level of pain/swelling in joints other than neck, back or hips; 4) Overall level of discomfort from any areas tender to touch or pressure; 5) Overall level of morning stiffness from time of awakening; 6) Duration of morning stiffness from time of awakening, and morning stiffness subscale.

  • Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) Independent Components at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    BASDAI subject rated components over last 48 hours using a 100 millimeter Visual Analog Scale; components 1-5: range 0=none to 100=very severe; component 6: range:0=0 hours to 100=2 hours or more. 1) Overall level of fatigue/tiredness experienced; 2) Overall level of AS neck,back or hip pain experienced; 3)Overall level of pain/swelling in joints other than neck,back or hips; 4) Overall level of discomfort from any areas tender to touch or pressure; 5) Overall level of morning stiffness from time of awakening; 6) Duration of morning stiffness from time of awakening.

  • Normalized Net Incremental Area Under the Curve (AUC) for Bath Ankylosing Spondylitis-Global Score (BAS-G) Visual Analog Scale Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BAS-G was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=none to 100=very important. Normalized net incremental area under the curve (AUC) = area between baseline and the BAS-G curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in the Bath Ankylosing Spondylitis-Global Score (BAS-G) at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject assessment of the effect of their disease on well-being over last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=very important.

  • Change From Baseline in the Bath Ankylosing Spondylitis-Global Score (BAS-G) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subject assessment of the effect of their disease on well-being over last 48 hours using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=very important.

  • Bath Ankylosing Spondylitis Global Score (BAS-G) Independent Component: Effect of Disease on Well-being at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject evaluation of the effect of their disease on well-being over the last week using a using a 100 millimeter Visual Anaog Scale; range: 0=none to 100=very important.

  • Change From Baseline to Week 12 in Forced Vital Capacity (FVC), Vital Capacity (VC), and Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 12 in Ratio Forced Expitatory Volume in One Second (FEV1)/Forced Vital Capacity (FVC) (%) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Metrology Index (BASMI) Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASMI was composed of 5 measures; each measure scored 0-2 (0=normal mobility, 2=severe reduction); final score range: 0 to 10. Normalized net incremental area under the curve (AUC) = area between baseline and the BASMI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Spinal Mobility Measured With the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. Higher score = greater reduction in spinal mobility.

  • Change From Baseline in Spinal Mobility Measured With the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. Higher score = greater reduction in spinal mobility.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Cervical Rotation at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Cervical rotation: measurement of degrees to which the subjects could turn their heads as far as possible to the right and then to the left. Mean of ordinal scores from 0: >= 85 degrees to 10: <= 8.5 degrees.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Cervical Rotation at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Cervical rotation: measurement in degree to which the subjects could turn their heads as far as possible to the right and then to the left. Mean of ordinal scores from 0: >= 85 degrees to 10: <= 8.5 degrees.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Tragus-to-wall Distance at Baseline and Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Measurement in centimeters (cm) of distance between the tragus and wall from right and left side while subject is standing with back against the wall; knees straight; scapulae, buttocks, and heels against the wall; with head in neutral position. Measurement of two attempts on right and left sides. Mean of ordinal scores from 0: <= 10 cm to 10: >= 37 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Tragus-to-wall Measurement at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Measurement in centimeters (cm) of distance between the tragus and wall from right and left side while subject is standing with back against the wall; knees straight; scapulae, buttocks, and heels against the wall; with head in neutral position. Measurement of two tries on right and left sides. Mean of ordinal scores from 0: <= 10 cm to 10: >= 37 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Lateral Flexion at Baseline and Weeks 2, 4, 8, and 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Measurement in centimters (cm) of distance between subject's middle fingertip and the floor after bending sideways, without bending knees or lifting heels, while attemting to keep shoulders in same place (flexion position). Measurement of two attempts on each side (right and left). Mean of ordinal scores from 0: >=20 cm to 10: <=1.2 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Lateral Flexion at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Measurement in centimters (cm) of distance between subject's middle fingertip and the floor after bending sideways, without bending knees or lifting heels, while attempting to keep shoulders in same place (flexion position). Measurement of two attempts on each side (right and left). Mean of ordinal scores from 0: >=20 cm to 10: <=1.2 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Modified Schober's Test at Baseline and Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Measurement in centimeters of the distance between marks originally placed while the subject was standing erect 10 centimeters (cm) above and 5 cm below the midpoint of a line that joints the posterior superior iliac spines. Distance between marks was remeasured with subject maximally bend forward, knees fully extended, with spine in full flexion. Measurement of two attempts. Mean of ordinal scores from 1: 5.7 to 6.3 cm, to 10: <=0.7 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Modified Schober's Test at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Measurement in centimeters of the distance between marks originally placed while the subject was standing erect 10 centimeters (cm) above and 5 cm below the midpoint of a line that joints the posterior superior iliac spines. Distance between marks was remeasured with subject maximally bend forward, knees fully extended, with spine in full flexion. Measurement of two attempts. Mean of ordinal scores from 1: 5.7 to 6.3 cm, to 10: <=0.7 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Intermalleolar Distance at Baseline and Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Measurement in centimeters (cm) of the distance between the medial malleoli when subject is lying supine with knees and feet straight up with legs separated as far as possible. Measurement of two attempts. Mean of ordinal scores from 0: >= 120 cm, to 9: 30 to 39.9 cm.

  • Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Intermalleolar Distance at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Measurement in centimeters (cm) of the distance between the medial malleoli when subject is lying supine with knees and feet straight up with legs separated as far as possible. Measurement of two attempts. Mean of ordinal scores from 0: >= 120 cm, to 9: 30 to 39.9 cm.

  • Normalized Net Incremental Area Under the Curve (AUC) for the Chest Expansion Test Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Normalized net incremental area under the curve (AUC) = area between baseline and the Chest Expansion Test curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in the Chest Expansion Test at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Measurement and remeasurement of standing maximal inspiration; chest circumference at nipple line or at 4th intercostal space in centimeters.

  • Change From Baseline in the Chest Expansion Test at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Measurement and remeasurement of standing maximal inspiration; chest circumference at nipple line or at 4th intercostal space in centimeters (cm).

  • Change From Baseline in Level of Difficulty to Perform Physically Demanding Activities Due to Ankylosing Spondylitis at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subject evaluation of level of difficulty to perform daily physical activities and/or kinesitherapy for ankylosing spondylitis (AS) because of AS using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=easy to 100=impossible. Subgroup of subjects who responded that they were able to perform daily physical activities and/or kinesitherapy for their ankylosing spondylitis at each visit.

  • Change From Baseline in Self Assessment of Ability and or Easiness to Perform Physically Demanding Activities at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subject evaluation of level of difficulty to perform daily physical activities and/or kinesitherapy for ankylosing spondylitis (AS) due to AS using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=easy to 100=impossible. Subgroup of subjects who responded that they were able to perform daily physical activities and/or kinesitherapy for their ankylosing spondylitis at each visit.

  • Normalized Net Incremental Area Under the Curve (AUC) for Erythtocyte Sedimentation Rate Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Normalized net incremental area under the curve (AUC) = area between baseline and the Erythrocyte Sedimentation Rate curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. A higher rate is consistent with inflammation.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. A higher rate is consistent with inflammation.

  • Normalized Net Incremental Area Under the Curve (AUC) for C-reactive Protein Between Baseline and Week 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Normalized net incremental area under the curve (AUC) = area between baseline and the C-reactive Protein curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.

  • Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12 [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    CRP is a marker of inflammation. A higher level is consistent with inflammation.

  • Change From Baseline in C-reactive Protein (CRP) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Change from baseline in C-reactive Protein (CRP).

  • Percent of Subjects With Normal and Abnormal C-Reactive Protein at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Percent of participants with normal (<6 milligrams per liter) and abnormal (>= 6 milligrams per liter) C-Reactive Protein.

  • Percent of Subjects With Patient Acceptable and Unacceptable Symptom State (PASS) at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Percent of subjects reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, subjects who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".

  • Percent of Subjects With Patient Acceptable and Unacceptable Symptom State (PASS) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Percent of subjects reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, subjects who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".

  • Percent of Subjects With Minimum Clinically Important Improvement (MCII) in Pain Rating at Weeks 2, 4, 8, 12 [ Time Frame: Week 2, Week 4, Week 8, Week 12 ] [ Designated as safety issue: No ]
    Subjects were asked how their pain had been during the last 48 hours compared to baseline. Those subjects that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.

  • Percent of Subjects With Minimum Clinially Important Improvement (MCII) at Weeks 14, 18, 24 [ Time Frame: Week 14, Week 18, Week 24 ] [ Designated as safety issue: No ]
    Subjects were asked how their pain had been during the last 48 hours compared to baseline. Those subjects that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.


Enrollment: 82
Study Start Date: January 2007
Study Completion Date: May 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Etanercept (Enbrel)
50 mg injection once weekly
Placebo Comparator: B Other: Placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Active and severe ankylosing spondylitis
  • Ankylosing spondylitis refractory to standard anti-rheumatic treatment
  • Between 18 and 70 years of age

Exclusion criteria

  • Prior exposure to any TNF-inhibitor, including etanercept
  • DMARDs (other than hydroxychloroquine, methotrexate and sulphasalazine) within 4 weeks of study drug initiation
  • Dose of NSAIDs changed within two weeks of study drug initiation
  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: NCT00420238

Locations
France
Amiens, France, 80094
Arles, France, 13200
Avignon, France, 84000
Bordeaux, France, 33076
Cabestany, France, 66330
Corbeil Essonnes, France, 91100
Montpellier, France, 34295
Nice, France, 6202
Orleans, France, 45032
Paris (Ambroise Pare), France, 92401
Paris (Bichat), France, 75018
Paris (COCHIN), France, 75679
Paris (Pitie Salpetriere), France, 75651
Paris (Saint Antoine), France, 75571
Strasbourg, France, 67098
Toulouse, France, 31000
Germany
Berlin, Germany, 12200
Herne, Germany, 446652
Hungary
Budapest, Hungary, 1023
Debrecen, Hungary, 4004
Netherlands
Maastricht, Netherlands, 6229 HX
Sponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Director: Medical Monitor Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: Trial Manager For France, infomedfrance@wyeth.com
Principal Investigator: Trial Manager For Germany, medinfoDEU@wyeth.com
Principal Investigator: Trial Manager For Netherlands, trials-NL@wyeth.com
Principal Investigator: Trial Manager For Hungary: WPBUMED@wyeth.com
  More Information

No publications provided by Wyeth is now a wholly owned subsidiary of Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
ClinicalTrials.gov Identifier: NCT00420238     History of Changes
Other Study ID Numbers: 0881A3-403
Study First Received: January 8, 2007
Results First Received: May 13, 2010
Last Updated: June 24, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Institutional Ethics Committee
Hungary: National Institute of Pharmacy
Netherlands: Independent Ethics Committee
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
Axial Ankylosing Spondylitis
Adult

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
TNFR-Fc fusion protein
Immunoglobulin G
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 25, 2014