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Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis (POSTURE)

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ClinicalTrials.gov Identifier: NCT01583374
Recruitment Status : Active, not recruiting
First Posted : April 24, 2012
Results First Posted : March 17, 2015
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE April 20, 2012
First Posted Date  ICMJE April 24, 2012
Results First Submitted Date  ICMJE February 24, 2015
Results First Posted Date  ICMJE March 17, 2015
Last Update Posted Date September 12, 2018
Actual Study Start Date  ICMJE May 2, 2012
Actual Primary Completion Date February 24, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) for the Comparison Between Apremilast 30 mg BID and Placebo at 16 Week of Treatment [ Time Frame: Baseline and Week 16 ]
ASAS 20 is defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are:
  1. Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active
  2. Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = "no pain" and the right-hand box = "most severe pain"
  3. Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability
  4. Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2012)
Assessment in Ankylosing Spondylitis (ASAS 20) [ Time Frame: Up to 16 weeks ]
ASAS 20 at Wk 16
Change History Complete list of historical versions of study NCT01583374 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2015)
  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The Bath Ankylosing Spondylitis Functional Index (BASFI) is a composite score based on a participant self-administered survey of ten questions using a 0 to 10 unit numerical rating scale (NRS) that assesses a participants' degree of mobility and functional ability. The questionnaire consists of eight questions regarding function in AS and the two last questions reflecting the participants' ability to cope with everyday life. The participant will be asked to mark the box with an X on a 0 to 10 unit NRS for each of the 10 questions, on which the left-hand box of 0 represents "easy," and the right-hand box represents "impossible." The resulting 0 to 100 score is divided by 10 to give a final 0 to 10 BASFI score. A higher BASFI score correlates to reduced functional ability.
  • Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a composite score based on a participant self-administered survey of six questions using a 0 to 10 unit numerical rating scale (NRS) that assesses the participants' five major symptoms of AS: 1) fatigue; 2) spinal pain; 3)peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening. The participant will be asked to mark the box with an X on a 0 to 10 unit NRS for each of the 6 questions. To give each of the five symptoms equal weighting, the mean of the two scores relating to morning stiffness is taken. The resulting 0 to 50 score is divided by 5 to give a final 0 to 10 BASDAI score. A BASDAI score of 4 or greater is considered to be indicative of active AS disease.
  • Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) at Week 24, Compared Between Apremilast 20 mg and Placebo [ Time Frame: Baseline and Week 24 ]
    ASAS 20 is defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are:
    1. Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active
    2. Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = "no pain" and the right-hand box = "most severe pain"
    3. Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability
    4. Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)
  • Change From Baseline in the Ankylosing Spondylitis Quality of Life (ASQoL) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The ASQoL is a validated disease specific patient reported outcomes instrument to assess the impact of ankylosing spondylitis (AS) on the quality of life of individuals with emphasis on the ability of the person to fulfill his or her needs. It consists of 18 items requesting a yes (score=1) or no (score=0) response to questions related to the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. The summary score ranges 0-18 with higher scores indicating worse quality of life
  • Change From Baseline in the Physical Component Summary Score (PCS) of Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement
  • Change From Baseline in Bath Ankylosing Spondylitis Metrology Index-Linear (BASMI-Linear) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The BASMI-Linear was designed to assess axial status (ie, cervical, dorsal and lumbar spine, hips, and pelvic soft tissue) and to define clinically significant changes in spinal movement. Five dimensions of movement (lateral lumbar flexion, tragus to wall, forward lumbar flexion, maximal intermalleolar distance, and cervical rotation) are measured and normalized on 0 to 10 unit NRS. The average of these scores is the total BASMI score, with a higher value indicating more severe limitation in spinal mobility
  • Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 104 [ Time Frame: Baseline and Week 104 ]
    The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) is a scoring method used by experts to determine the amount or degree of ankylosing spondylitis disease that is in the spine based on x-ray radiographs of the spine.
  • Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 260 [ Time Frame: Baseline and Week 260 ]
    The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) is a scoring method used by experts to determine the amount or degree of ankylosing spondylitis disease that is in the spine based on x-ray radiographs of the spine.
  • Number of Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Period [ Time Frame: During placebo-controlled period; up to week 24 ]
    A TEAE is an adverse event with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for participants who discontinued early. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2012)
  • Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Up to 24 weeks ]
    Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
  • Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Up to 24 weeks ]
    Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)
  • Assessment in Ankylosing Spondylitis (ASAS 20) [ Time Frame: Up to 24 weeks ]
    Assessment in Ankylosing Spondylitis (ASAS 20)
  • Change from baseline in the Physical Component Summary score (PCS) of Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) [ Time Frame: Up to 24 weeks ]
    Change from baseline in the Physical Component Summary score (PCS) of Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36)
  • Change from baseline in Bath Ankylosing Spondylitis Metrology Index-linear (BASMI-lin) [ Time Frame: Up to 24 weeks ]
    Change from baseline in Bath Ankylosing Spondylitis Metrology Index-linear (BASMI-lin)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis
Official Title  ICMJE A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN THE TREATMENT OF ACTIVE ANKYLOSING SPONDYLITIS
Brief Summary Apremilast is a new, orally available, small molecule drug that specifically inhibits phosphodiesterase 4 (PDE4), an enzyme that modulates inflammatory cytokines. This clinical study tests whether apremilast can improve the signs and symptoms of ankylosing spondylitis.
Detailed Description Patients will be assigned two different treatments based on chance (randomized) to placebo or apremilast (20 or 30 mg tablet). The duration of the study is approximately 5 years. The double blind period (when patients nor the physician knows whether placebo or apremilast is taken) is 24 weeks. At Week 16, subjects who do not have either a ≥ 20% improvement or a ≥ 1 unit improvement from baseline in at least two of the four SpondyloArthritis international Society (ASAS) domains will enter the "early escape" from their current treatment in a double-blinded manner. However, such subjects will be permitted to continue in the study. At Week 24, subjects may enter a long-term extension phase for up to an additional 4.5 years (236 weeks). At "second escape" (at Week 24), apremilast 20 mg BID treated subjects will be transitioned to receive double-blinded apremilast 30 mg BID; apremilast 30 mg BID will remain on double-blinded apremilast 30 mg BID because they may continue to improve with a longer duration of treatment. After Week 24 and during the early portion of the long-term extension through Week 52, all subjects will continue on either double-blinded apremilast 20 mg BID or 30 mg BID treatment. After all subjects have completed Week 52 or have terminated early from the study and the 52-week data base is locked, open-label apremilast 20 mg BID or 30 mg BID treatment will be provided.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ankylosing Spondyloarthritis
Intervention  ICMJE
  • Drug: Apremilast tablet 20 mg
    PDE4-specific inhibitor
  • Drug: Apremilast tablet 30 mg BID
    PDE4-specific inhibitor
  • Drug: Placebo
    PDE4-specific inhibitor
Study Arms  ICMJE
  • Experimental: Apremilast 20 mg
    Apremilast 20 mg will be taken orally twice a day (BID)
    Intervention: Drug: Apremilast tablet 20 mg
  • Experimental: Apremilast 30 mg
    Apremilast 30 mg will be taken orally twice a day (BID)
    Intervention: Drug: Apremilast tablet 30 mg BID
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 24, 2016)
490
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2012)
456
Estimated Study Completion Date  ICMJE October 2, 2018
Actual Primary Completion Date February 24, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented diagnosis of Definite Ankylosing Spondylitis [(AS); arthritis of the spine]
  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is ≥ 4
  • Total back pain is ≥ 4
  • On stable dose of AS medication (or lack of medication) prior to randomization and through week 24

Exclusion Criteria:

  • Prior treatment with a Tumor Necrosis Factor (TNF) blocker and any biologic treatment for AS
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Bulgaria,   Canada,   Czechia,   Estonia,   France,   Germany,   Hungary,   Netherlands,   Poland,   Romania,   Russian Federation,   Slovakia,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01583374
Other Study ID Numbers  ICMJE CC-10004-AS-001
2011-001555-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Lilia Pineda, MD Celgene Corporation
PRS Account Celgene
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP