Study Comparing Etanercept (ETN) Against a Placebo for Etanercept on a Background Nonsteroidal Anti Inflammatory Drug (NSAIDs) in the Treatment of Early Spondyloarthritis (SpA) Patients Who do Not Have X-ray Structural Changes (EMBARK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01258738
First received: December 9, 2010
Last updated: September 14, 2015
Last verified: September 2015
  Purpose
This is a two part study. During period one there will be a comparison of Etanercept (ETN) against a placebo with both arms maintaining the background anti inflammatory drug prescribed by their Physician. The hypothesis is that Etanercept will be superior to the placebo arm as determined by the proportion of subjects achieving Assessments in Ankylosing Spondylitis (ASAS)40 improvement at 12 weeks. This will be followed by 92 weeks extension where everyone in the trial receives Etanercept (ETN) and a background non steroidal anti inflammatory drug(NSAID).

Condition Intervention Phase
Spondylitis, Ankylosing
Biological: etanercept
Drug: Background NSAID
Other: PLACEBO
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicentre, 12 Week Double Blind Placebo Controlled Randomized Study Of Etanercept On A Background Nsaid In The Treatment Of Adult Subjects With Non Radiographic Axial Spondyloarthritis With A 92 Week Open Label Extension

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Achieving Ankylosing Spondylitis (ASAS) 40 Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 scale (0 = no disease activity, 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.


Secondary Outcome Measures:
  • Percentage of Participants Achieving ASAS 40 Response at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in AS in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 scale (0 = no disease activity, 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants Achieving ASAS 20 Response at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in AS in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement from baseline and an absolute change ≥ 10 units on a 0-100 scale (0=no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants Achieving ASAS 5/6 Response at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (participant global assessment of disease activity, pain, function, inflammation measured on a 0-100 scale, where 0 = no disease activity and 100 = high disease activity) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains and no worsening in the remaining domain.

  • Mean Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) High Sensitivity CRP (hsCRP) Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    ASDAS includes CRP (mg/L) or ESR (mm/hr); Apart from the value of CRP or ESR, the four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included in this index are back pain, duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity. The ASDAS scores are then calculated as follows: ASDAS_CRP = (0.121 x total back pain) + (0.110 x subject global) + (0.073 x peripheral pain/swelling) + (0.058 x duration of morning stiffness) + (0.579 x Ln(CRP+1)). And ASDAS_ESR: (0.079 x total back pain) + (0.113 x subject global) + (0.086 x peripheral pain/swelling) + (0.069 x duration of morning stiffness) + (0.293 x √ESR). In addition, the proportion of participants who achieve inactive disease based on the ASDAS will be determined for each group. Inactive disease is defined as an ASDAS score <1.3.

  • Percentage of Participants Achieving ASAS Partial Remission at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Partial remission defined as a score of 20 units or less (on a scale of 0-100, where 0 = no disease activity and 100 = high disease activity) in each of the 4 Assessment in ASAS domains: participant global assessment of disease activity, pain, function, and inflammation. For scale, 100 = high disease activity.

  • Time to ASAS Partial Remission [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The median time to partial remission was not reached at Week 12. Hence, we report an estimate of the percentage of participants, estimated using Kaplan-Meier approach.

  • Mean Change From Baseline in Visual Analogue Scale (VAS) Physician Global Assessments at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The Investigator estimated the participant's overall disease activity over the previous 48 hours (this was independent of the Subject Assessment of Disease Activity) using a scale between 0 mm (none) and 100 mm (severe).

  • Mean Change From Baseline in VAS Score for Subject Assessment of Disease Activity at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Participants to assess their overall disease activity over the last 48 hours using a pain scale between 0 mm (none) and 100 mm (severe), which corresponded to the magnitude of their pain.

  • Changes From Baseline in VAS Score for Nocturnal Back Pain at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The VAS scale was used to assess the level of nocturnal pain during the past 48 hours. For this, participants marked their level of pain on a 100 mm VAS anchored by 0 for "No pain " to 100 mm for "Most Severe Pain."

  • Changes From Baseline in VAS Score for Total Back Pain at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The VAS scale was used to assess the level of total back pain during the past 48 hours. For this, participants marked their level of pain on a 100 mm VAS anchored by 0 for "No pain " to 100 mm for "Most Severe Pain."

  • Changes From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Full Day Activities at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Bending Forward at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Getting Out of an Arm-less Chair at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Physically Demanding Activities at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Reaching up High at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Climbing Steps Without Aid at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Getting-up Off-floor From Back at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Standing Unsupported for 10 Minutes at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Looking Over Shoulder at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Mean Change From Baseline in BASFI Putting on Socks at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

  • Changes From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Total Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of Morning Stiffness at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of Fatigue/Tiredness at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of Discomfort at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of How Long Stiffness Lasts at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of Pain/Swelling at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Mean Change From Baseline in BASDAI Level of Neck/Back/Hip Pain at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment tool used to determine disease activity in participant with Ankylosing Spondylitis (AS). Utilizing a VAS of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5. The final BASDAI score averages the individual assessments for a final score range of 0-10.

  • Percentage of Participants With BASDAI 50 at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Response was defined as a 50% improvement of the Baseline BASDAI to 104 weeks of study treatment, respectively. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5.

  • Percentage of Participants With BASDAI 20 at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Response was defined as a 20% improvement of the Baseline BASDAI to 104 weeks of study treatment. The BASDAI score is obtained by computing the mean score for the 2 questions related to morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for the first 4 questions and then dividing the total by 5. This can be written as BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5.

  • Change From Baseline in Bath Ankylosing Spondylitis Global Index (BAS-G) Total Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The BAS-G was a 2 question assessment evaluating the effect of AS on the participants well-being over the last week and last 6 months. The 2 questions were: How have you been over the last week? and How have you been over the last six months?. Each question is scored by the participant on a 100 mm scale ranging from 0 (Very Good) to 100 (Very Bad). The two values are averaged to obtain the BAS-G score.

  • Mean Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Total Score at Time Points [ Time Frame: Baseline to Week 104 ] [ 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.

  • Mean Change From Baseline in BASMI Lateral Side Flexion Score by Time Point [ Time Frame: Baseline to Week 104 ] [ 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.

  • Mean Change From Baseline in BASMI Cervical Rotation Degree by Time Point [ Time Frame: Baseline to Week 104 ] [ 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.

  • Mean Change From Baseline in BASMI Modified Schobers Test Score by Time Point [ Time Frame: Baseline to Week 104 ] [ 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.

  • Mean Change From Baseline in BASMI Intermalleolar Distance Score by Time Point [ Time Frame: Baseline to Week 104 ] [ 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.

  • Mean Change From Baseline in BASMI Tragus to Wall Score by Time Point [ Time Frame: Baseline to Week 104 ] [ 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.

  • Change From Baseline in Chest Expansion at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Chest expansion, measured in cm, is defined as the difference in thoracic circumference during full expiration versus full inspiration, measured at the fourth intercostal space (nipple line). At maximal inspiration, the chest circumference was measured at nipple line or at the 4th intercostal space (in cm to the nearest 0.1 cm).

  • Mean Change From Baseline in Occiput-to-wall Test at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Occiput-to-wall distance: distance between the occiput (posterior or back portion of the head) and the wall when the participant stood with heels and shoulder against the wall and the back straight.

  • Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) - Spine 6 Discovertebral Units (DVU) Total Score at 12 Weeks [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The change from baseline in the MRI score of spine was assessed using SPARCC method. The scores of the 6 most severely affected spinal levels (discovertebral units/DVUs) was selected. Each DVU was divided into 4 quadrants. Each quadrant was assigned a score of 0 = no lesion or 1 = increased signal. This was repeated for each of 3 consecutive sagittal slices resulting in a score of up to 12 per DVU. On each slice, the presence of a lesion exhibiting an intense signal in any quadrant was assigned an additional score of 1 for that slice. Additionally, on each slice the presence of a lesion exhibiting depth ≥ 1 cm in any quadrant was given an additional score of 1. The maximum score for 6 DVU Spine Total Score is 108.

  • Mean Change From Baseline in SPARCC Score for the Sacroiliac Joint at Time Points [ Time Frame: Weeks 12 and 104 ] [ Designated as safety issue: No ]
    The change from baseline in the MRI score of sacroiliac joints was assessed using SPARCC method. Scoring was based on 6 consecutive coronal slices from posterior to anterior. Each joint was divided into 4 quadrants. Each quadrant was assigned a score of 0 = no lesion/1 = increased signal. For each slice, the score is increased by 1 for each joint that exhibits an intense signal in any quadrant. Also, for each slice, an additional score of 1 will be given for each joint that includes a lesion demonstrating continuous increased signal of a depth ≥1 cm from the articular surface. The maximum possible score is 72.

  • Mean Change From Baseline in SPARCC - Spine 6 Discovertebral Units (DVU) Total Score at Time Points [ Time Frame: Weeks 12 and 104 ] [ Designated as safety issue: No ]
    The change from baseline in the MRI score of spine was assessed using SPARCC method. The scores of the 6 most severely affected spinal levels (discovertebral units/DVUs) was selected. Each DVU was divided into 4 quadrants. Each quadrant was assigned a score of 0 = no lesion or 1 = increased signal. This was repeated for each of 3 consecutive sagittal slices resulting in a score of up to 12 per DVU. On each slice, the presence of a lesion exhibiting an intense signal in any quadrant was assigned an additional score of 1 for that slice. Additionally, on each slice the presence of a lesion exhibiting depth ≥ 1 cm in any quadrant was given an additional score of 1. The maximum score for 6 DVU Spine Total Score is 108.

  • Mean Change From Baseline in Ankylosing Spondylitis Spine Magnetic Resonance Imaging-Activity (ASspiMRI-a) Total Score [ Time Frame: Weeks 12 and 104 ] [ Designated as safety issue: No ]
    ASspiMRI-a measures acute lesion scores as determined by short-tau inversion recovery (STIR) and gadolinium-enhanced T1 (Gd-DTPA). All 23 disco-vertebral units (DVU) of the spine (from C2 to S1), defined as the region between 2 virtual lines through the middle of each vertebra, are scored in a single dimension, which is representing the highest level of inflammation in that particular DVU. Enhancement and bone marrow edema are graded (0-3) for each DVU, with 3 more grades (4-6) if, in addition to the signs of acute inflammation defined for grades 1-3, erosions are visualized, leading to a maximum score of 138 for the entire spine. Acute spinal changes were assessed by using STIR sagittal views of the cervical, thoracic and lumbar spine. The total score ranges from 0 (no inflammation) to 138 (high inflammation).

  • Mean Change From Baseline in Number of Swollen Joints at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Forty-four (44) joints were assessed by the Investigator to determine the number of joints that were considered swollen (artificial joints were not assessed). The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done. The 44 joints to be assessed were:sternoclavicular, acromioclavicular, shoulder, elbow, wrist (includes radiocarpal, carpal and carpometacarpal considered as one unit), metacarpophalangeals (I, II, III, IV, V), thumb interphalangeal (IP), proximal IPs (II, III, IV, V), knee, ankle, metatarsophalangeals (I, II, III, IV, V).

  • Mean Change From Baseline in Number of Tender Joints at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Forty-four (44) joints were assessed by the Investigator to determine the number of joints that were considered tender or painful. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be considered for artificial joints). The 44 joints to be assessed were:sternoclavicular, acromioclavicular, shoulder, elbow, wrist (includes radiocarpal, carpal and carpometacarpal considered as one unit), metacarpophalangeals (I, II, III, IV, V), thumb interphalangeal (IP), proximal IPs (II, III, IV, V), knee, ankle, metatarsophalangeals (I, II, III, IV, V).

  • Mean Change From Baseline in Dactylitis Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Each of the 10 fingers and 10 toes is evaluated for dactylitis. A score of 0, 1, 2 or 3 (where 0 = none, 1= mild, 2 = moderate, 3 = severe) is assigned to each. A total score which can range from 0 to 60 is obtained by adding the scores for the 20 digits

  • Changes From Baseline in Maastricht Ankylosing Spondylitis Enthesis Score (MASES) at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness).

  • Change From Baseline in C-reactive Protein (CRP) Concentration Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Time Points [ Time Frame: Baseline to Week 104 ] [ 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. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.

  • Change From Baseline in Euro Quality of Life (EQ)-5D VAS Score Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.

  • Change From Baseline in EQ-5D Health State Profile Utility Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  • Change From Baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) at Time Points [ Time Frame: Baseline to Week 104 ] [ 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, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100 = highest level of functioning).

  • Change From Baseline in SF-36 Mental Component Summary (MCS) at Time Points [ Time Frame: Baseline to Week 104 ] [ 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, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    This outcome measure is describing the HADS subscale of depression. HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. There is no Total Score for HADS.

  • Change From Baseline in HADS Anxiety Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    This outcome measure is describing the HADS subscale of anxiety. HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. There is no Total Score for HADS.

  • Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    ASQoL is a questionnaire that assesses disease-specific quality of life (QoL). It consists of 18 statements that are relevant to the physical and mental conditions for a participant with Ankylosing Spondylitis (AS): mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL).

  • Change From Baseline in Ankylosing Spondylitis Work Instability Index (AS-WIS) Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The AS-WIS is a 20 item questionnaire to assess work disability and risk of unemployment due to AS. Higher scores indicate greater work impairment and instability that results from a mismatch between an individual's ability levels given their AS and their job. Each question is assigned a score of 1 for a response of "True" and 0 for a response of "Not True". All item scores are summed to give a total score that can range from 0 to 20. If a subject has ≥ 5 missing responses (ie more than 20%), then a total score is not calculated. For subjects with ≥ 1 but ≤ 4 missing responses, the total score is calculated as follows: T=20x/(20-m) where: T is the total score, x is the total score for the items answered and n is the number of non-missing items.

  • Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed Due to Health Problems at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: Yes ]

    The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated:

    Percent work time missed due to health problem: Q2/(Q2+Q4). The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity.


  • Change From Baseline in WPAI: Percent Impairment While Working Due to Health Problems at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]

    The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated:

    Percent impairment while working due to health problem: Q5/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity.


  • Changes From Baseline in WPAI - Activity Impairment Due to Health Problems at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]

    The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated:

    Percent activity impairment due to health problem: Q6/10. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity.


  • Changes From Baseline in WPAI - Overall Work Impairment Due to Health Problems at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]

    The WPAI assesses work productivity and impairment. It is a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days. The questions are: Q1 = currently employed. Q2 = hours missed due to health problems. Q3 = hours missed other reasons. Q4 = hours actually worked. Q5 = degree health affected productivity while working (0-10 scale). Q6 = degree health affected regular activities (0-10 scale). Subscale scores are calculated:

    Percent overall work impairment due to health problem:

    Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))*(Q5/10)]. The computed percentage range for each sub-scale is 0-100, where higher numbers indicate greater impairment and less productivity.


  • Change From Baseline in Multidimensional Fatigue Inventory (MFI) Score at Time Points [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The MFI is a 20-item questionnaire that evaluates several aspects of fatigue. The General Fatigue Item is disclosed here. The general fatigue item contains four items, two of which are indicative for fatigue and two items contra-indicative for fatigue. Indicative items (eg, "I tire easily") are formulated in such a way that a high score suggests a high degree of fatigue. In case of contra-indicative items (eg, "I feel fit") a high score indicates a low degree of fatigue. Each item is scored on a 5-point numeric rating scale anchored at each end by "Yes, that is true" (scored 1) to "No, that is not true" (scored 5). Scoring for the MFI is done in such a way that higher scores indicate greater fatigue. Therefore, the items indicative for fatigue need to be recoded (1=5, 2=4, 3=3, 4=2, 5=1). For each scale a total score is calculated by summation of the scores of the individual items. Scores can range from the minimum of 4 to the maximum of 20. MFI-20 scale is copyrighted.

  • Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Score From Baseline to Week 104 [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    The MOS sleep scale consists of 12 items to measure 6 sleep dimensions: initiation (time to fall asleep), quantity (hours of sleep each night), maintenance, respiratory problems, perceived adequacy, somnolence (the last 4 items reported using a 6-item Likert scale ranging from 1 [all of the time] to 6 [none of the time]). The raw scores ranging from 1 to 6 are transformed to scores ranging from 0 to 100 before the indices are calculated. Therefore the reported scores, consisting of means of converted items, also range from 0 to 100. However, two indexes can be derived: Sleep problems index I (short form) and sleep problems index II (long form). Additional subscales can be derived: sleep disturbance, snoring, awaken shortness of breath or headache, sleep adequacy, sleep somnolence, sleep quantity, and optimal sleep. However, data for two indexes and additional subscales is not reported.

  • Percentage of Participants With Minimally Clinically Important Improvement (MCII) at Time Points [ Time Frame: Weeks 12 and 104 ] [ Designated as safety issue: No ]
    The MCII asks participants to rate the level of improvement they have experienced in the 48 hours compared to when they started the study. Response options are "Improved - less pain", "No change", and "Worse - more pain." If the participant indicates that improvement has occurred, then they are asked to indicate how important that improvement is to them from "Not at all important" to "Very important'.

  • Percentage of Participants Achieving Patient Acceptable Symptom State (PASS) at Time Points [ Time Frame: Weeks 12 and 104 ] [ Designated as safety issue: No ]
    PASS is defined as a symptom state that the participants consider acceptable.


Enrollment: 225
Study Start Date: February 2011
Study Completion Date: October 2014
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: etanercept
In Period 1 : Subjects will receive via a prefilled syringe an active dose equivalent to 1.0ml of Etanercept solution once weekly SC once weekly. Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Biological: etanercept
In Period 1, subjects will receive in a prefilled syringe with 1.0 ml (test article Etanercept (SC) once weekly . Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Other Name: ENBREL
Drug: Background NSAID
Subject will continue to take a concomitant background non steroidal anti inflammatory drug(NSAID)as prescribed by their attending physician. The name and dose of this NSAID is the decision of the attending physician.
Placebo Comparator: PLACEBO
In Period 1: Subjects will receive in a prefilled syringe with a PLACEBO dose equivalent to 1.0 ml of placebo solution once weekly SC Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Other: PLACEBO
In Period 1 will receive a prefilled syringe of Placebo for Etanercept Additionally they will continue to take the background non steroidal anti inflammatory drug(NSAID) in the tolerated dose agreed upon by the attending Physician.
Drug: Background NSAID
Subject will continue to take a concomitant background non steroidal anti inflammatory drug(NSAID)as prescribed by attending physician (dose drug selection as tolerated and agreed upon by the attending Physician).

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of axial spondyloarthritis as defined by Assessments in Ankylosing Spondylitis (ASAS)criteria
  • Active symptoms defined as Ankylosing Spondylitis Disease Activity Index{BASDAI) > or = 4
  • Axial symptoms of back pain with a less than favorable response to on steroidal anti inflammatory drugs at optimal dosage for greater than 4 weeks

Exclusion Criteria:

  • Evidence of current or recent episode of uveitis
  • Evidence of IBD flare within 6 months
  • Previous treatment with an anti Tumor necrosis factor(TNF)
  • Active tuberculosis
  • Radiographic sacroiliitis grade 3-4 unilaterally or >= 2 bilaterally
  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: NCT01258738

  Show 50 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01258738     History of Changes
Other Study ID Numbers: B1801031  0881A3-4725  2010-020077-16 
Study First Received: December 9, 2010
Results First Received: November 11, 2013
Last Updated: September 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Early ankylosing spondylitis (SpA) study; efficacy and safety and health out comes

Additional relevant MeSH terms:
Spondylitis
Spondylarthritis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Arthritis
Joint Diseases
Spondylarthropathies
Ankylosis
Etanercept
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 28, 2016