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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Ankylosing Spondyloarthritis
Interventions Drug: Apremilast tablet 20 mg
Drug: Apremilast tablet 30 mg BID
Drug: Placebo
Enrollment 490
Recruitment Details This is an ongoing study consisting of a 24-week randomized, double-blind, placebo-controlled phase evaluating two doses of Apremilast (20 mg and 30mg) compared to placebo in those with active ankylosing spondylitis, followed by a double-blind, long-term extension treatment phase (236 weeks) 4.5-years for an overall study duration of 5 years.
Pre-assignment Details

Randomized participants were stratified by the following 2 parameters:

  1. C-Reactive Protein (CRP) concentration (normal: ≤ 1.5 mg/dl or elevated: > 1.5 mg/dl) from screening;
  2. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score < 6.0 or BASDAI score ≥ 6.0 from baseline.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description Participants initially randomized to placebo by mouth (PO) twice daily (BID) in the 24-week placebo-controlled treatment phase. Participants initially randomized to 20 mg apremilast PO BID in the 24-week placebo-controlled treatment phase. Participants initially randomized to 30 mg apremilast PO BID in the 24-week placebo-controlled treatment phase.
Period Title: Overall Study
Started 164 163 163
Received Treatment 164 163 163
Completed Week 16 150 151 144
Early Escape at Week 16 51 [1] 49 49 [1]
Completed 145 [2] 147 [2] 138 [2]
Not Completed 19 16 25
Reason Not Completed
Adverse Event             6             7             12
Lack of Efficacy             3             2             5
Non-compliance with study drug             1             1             0
Withdrawal by Subject             8             3             5
Lost to Follow-up             1             2             0
Protocol Violation             0             0             3
Other             0             1             0
[1]
One participant who escaped early did not complete Week 24
[2]
Completed = those who completed the Placebo-controlled Treatment Phase – Weeks 0 to 24
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg Total
Hide Arm/Group Description Participants initially randomized to placebo by mouth (PO) twice daily (BID) in the 24-week placebo-controlled treatment phase. Participants initially randomized to 20 mg apremilast PO BID in the 24-week placebo-controlled treatment phase. Participants initially randomized to 30 mg apremilast PO BID in the 24-week placebo-controlled treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 164 163 163 490
Hide Baseline Analysis Population Description
Modified Intent to Treat (mITT) were all participants who were randomized and received at least one dose of investigational product (IP)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 163 participants 163 participants 490 participants
44.0  (12.89) 45.2  (11.90) 44.8  (11.75) 44.7  (12.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 163 participants 163 participants 490 participants
Female
40
  24.4%
42
  25.8%
56
  34.4%
138
  28.2%
Male
124
  75.6%
121
  74.2%
107
  65.6%
352
  71.8%
Duration of Ankylosing Spondylitis (Lower Back Pain and Stiffness)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 163 participants 163 participants 490 participants
10.39  (10.373) 11.06  (11.302) 10.31  (9.882) 10.59  (10.519)
Duration of Ankylosing Spondylitis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 164 participants 163 participants 163 participants 490 participants
≤ 2 years 41 48 40 129
> 2 to ≤ 5 years 29 23 26 78
> 5 to ≤ 10 years 33 29 33 95
> 10 years 61 63 64 188
1.Primary Outcome
Title 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
Hide Description

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)
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population who were randomized to apremilast (APR) 30 mg BID or placebo and received at least one dose of investigational product. The APR 20mg dose was an exploratory endpoint.
Arm/Group Title Placebo Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to placebo by mouth (PO) twice daily (BID) in the 24-week placebo-controlled treatment phase.
Participants initially randomized to 30 mg apremilast PO BID in the 24-week placebo-controlled treatment phase.
Overall Number of Participants Analyzed 164 163
Measure Type: Number
Unit of Measure: percentage of participants
36.6 32.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4383
Comments Adjusting for CRP category and baseline BASDAI score category
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-14.3 to 6.2
Estimation Comments Adjusted difference in proportions is the weighted average of the treatment differences across the 4 strata of screening CRP category and baseline BASDAI score category with the Cochran-Mantel-Haenszel weights
2.Secondary Outcome
Title Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24
Hide Description 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.
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
Hide Description 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.
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) at Week 24, Compared Between Apremilast 20 mg and Placebo
Hide Description

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)
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change From Baseline in the Ankylosing Spondylitis Quality of Life (ASQoL) at Week 24
Hide Description 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
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
6.Secondary Outcome
Title 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
Hide Description 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
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Change From Baseline in Bath Ankylosing Spondylitis Metrology Index-Linear (BASMI-Linear) at Week 24
Hide Description 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
Time Frame Baseline and Week 24
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 104
Hide Description 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.
Time Frame Baseline and Week 104
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 260
Hide Description 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.
Time Frame Baseline and Week 260
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Number of Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Period
Hide Description 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.
Time Frame During placebo-controlled period; up to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population includes all participants who were randomized and received at least one dose of IP. Includes data through Week 16 for placebo-treated and apremilast 20 mg BID treated participants who escaped early and data up to Week 24 for all other participants.
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description:
Participants initially randomized to receive placebo tablets twice daily.
Participants initially randomized to 20 mg apremilast PO BID in the 24-week placebo-controlled treatment phase.
Participants initially randomized to 30 mg apremilast PO BID in the 24-week placebo-controlled treatment phase..
Overall Number of Participants Analyzed 164 163 163
Measure Type: Number
Unit of Measure: participants
Any Treatment Emergent Adverse Event (TEAE) 82 89 85
Any drug-related TEAE 21 43 49
Any severe TEAE 0 2 5
Any serious TEAE 1 3 6
Any serious drug-related TEAE 0 0 3
Any TEAE leading to drug interruption 13 12 13
Any TEAE leading to drug withdrawal 6 9 12
Time Frame Adverse events are reported for the placebo-controlled phase; up to 21 months counting from the first dose of the first participant .
Adverse Event Reporting Description Includes data through Week 16 for placebo-treated and apremilast 20 mg BID treated participants who escaped early and data up to Week 24 for all other participants.
 
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg
Hide Arm/Group Description Participants initially randomized to receive placebo tablets twice daily. Participants initially randomized to receive 20 mg apremilast tablets twice daily in the 24-week placebo controlled treatment phase. Participants initially randomized to receive 30 mg apremilast tablets twice daily in the 24-week placebo controlled treatment phase.
All-Cause Mortality
Placebo Apremilast 20 mg Apremilast 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Apremilast 20 mg Apremilast 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/164 (0.61%)   3/163 (1.84%)   6/163 (3.68%) 
Cardiac disorders       
Sick sinus syndrome  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Ear and labyrinth disorders       
Vertigo  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Eye disorders       
Uveitis  1  0/164 (0.00%)  1/163 (0.61%)  0/163 (0.00%) 
Gastrointestinal disorders       
Abdominal hernia  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Abdominal pain upper  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
General disorders       
Chest pain  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Hepatobiliary disorders       
Alcoholic liver disease  1  0/164 (0.00%)  1/163 (0.61%)  0/163 (0.00%) 
Injury, poisoning and procedural complications       
Cardiac function disturbance postoperative  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Musculoskeletal and connective tissue disorders       
Ankylosing spondylitis  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant melanoma  1  1/164 (0.61%)  0/163 (0.00%)  0/163 (0.00%) 
Psychiatric disorders       
Depression  1  0/164 (0.00%)  0/163 (0.00%)  1/163 (0.61%) 
Renal and urinary disorders       
Calculus urinary  1  0/164 (0.00%)  1/163 (0.61%)  0/163 (0.00%) 
Renal colic  1  0/164 (0.00%)  1/163 (0.61%)  0/163 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Apremilast 20 mg Apremilast 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/164 (15.24%)   39/163 (23.93%)   45/163 (27.61%) 
Gastrointestinal disorders       
Diarrhoea  1  5/164 (3.05%)  20/163 (12.27%)  15/163 (9.20%) 
Nausea  1  6/164 (3.66%)  10/163 (6.13%)  14/163 (8.59%) 
Abdominal pain upper  1  3/164 (1.83%)  3/163 (1.84%)  9/163 (5.52%) 
Infections and infestations       
Nasopharyngitis  1  6/164 (3.66%)  9/163 (5.52%)  7/163 (4.29%) 
Nervous system disorders       
Headache  2  8/164 (4.88%)  9/163 (5.52%)  16/163 (9.82%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
2
Term from vocabulary, MedDRA14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally sixty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.
Results Point of Contact
Name/Title: Anne McClain, Senior Study Manager
Organization: Celgene Corporation
Phone: 888-260-1599
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01583374     History of Changes
Other Study ID Numbers: CC-10004-AS-001
2011-001555-37 ( EudraCT Number )
First Submitted: April 20, 2012
First Posted: April 24, 2012
Results First Submitted: February 24, 2015
Results First Posted: March 17, 2015
Last Update Posted: September 12, 2018