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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

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.

Condition or disease Intervention/treatment Phase
Ankylosing Spondyloarthritis Drug: Apremilast tablet 20 mg Drug: Apremilast tablet 30 mg BID Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 490 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 2, 2012
Actual Primary Completion Date : February 24, 2014
Estimated Study Completion Date : October 2, 2018


Arm Intervention/treatment
Experimental: Apremilast 20 mg
Apremilast 20 mg will be taken orally twice a day (BID)
Drug: Apremilast tablet 20 mg
PDE4-specific inhibitor

Experimental: Apremilast 30 mg
Apremilast 30 mg will be taken orally twice a day (BID)
Drug: Apremilast tablet 30 mg BID
PDE4-specific inhibitor

Placebo Comparator: Placebo
Placebo
Drug: Placebo
PDE4-specific inhibitor




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01583374


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Locations
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United States, Arizona
Sun Valley Arthritis Center
Peoria, Arizona, United States, 85381
United States, California
UCSD-Thornton Hospital
La Jolla, California, United States, 92093-0943
Desert Medical Advances
Palm Desert, California, United States, 92260
University of California, San Francisco
San Francisco, California, United States, 94143-0326
United States, Florida
Advent Clinical Research
Pinellas Park, Florida, United States, 33781
Tampa Medical Group Pa
Tampa, Florida, United States, 33614
Alastair Kennedy, MD Research
Vero Beach, Florida, United States, 32962
United States, Illinois
Northwestern Center For Clinical Research
Chicago, Illinois, United States, 60611
United States, Maryland
Klein and Associates MD, PA
Hagerstown, Maryland, United States, 21740
United States, Massachusetts
Clinical Pharmacology Study Group
Worcester, Massachusetts, United States, 01610
United States, Minnesota
Saint Paul Rheumatology, PA
Eagan, Minnesota, United States, 55121
United States, Ohio
MetroHealth Medical Systems
Cleveland, Ohio, United States, 44109
STAT Research, Inc.
Dayton, Ohio, United States, 45417
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
United States, Tennessee
The Arthritis Clinic
Jackson, Tennessee, United States, 38305
Ramesh C Gupta MD
Memphis, Tennessee, United States, 38119
United States, Texas
Austin Regional Clinic
Austin, Texas, United States, 78731
Baylor Research Institute
Dallas, Texas, United States, 75231
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Rheumatology and Immunotherapy Center
Franklin, Wisconsin, United States, 53132
Australia, Tasmania
Southern Clinical Research
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Emeritus Research
Camberwell, Victoria, Australia, 3124
Australia
Coastal Joint Care
Maroochydore, Australia, 4558
Royal Perth Hospital
Perth, Australia, 6849
Central Northern Adelaide Health Services Ethics of Human Research Committee TQEH and LMH
Woodville South, Australia, 5011
Austria
Krankenhaus Wien-Hietzing
Wien, Austria, 1130
Bulgaria
Diagnostic and Consulting Center Sv. Pantaleymon
Pleven, Bulgaria, 5800
National Multiprofile Transport Hospital Tzar Boris III
Sofia, Bulgaria, 1233
17 Diagnostic and Consulting Centre
Sofia, Bulgaria, 1505
Military Medical Academy - MHAT
Sofia, Bulgaria, 1606
Diagnostic Consulting Center N4
Varna, Bulgaria, 9010
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 1N4
Canada, Newfoundland and Labrador
Nexus Clinical Research
St John's, Newfoundland and Labrador, Canada, A1B 3E1
Canada, Ontario
MAC Research Incorporated
Hamilton, Ontario, Canada, L8N 2B6
William Bensen's Private Practice
Hamilton, Ontario, Canada, L8N1Y2
Credit Valley Professional Building
Mississauga, Ontario, Canada, L5M 2V8
The Arthritis Program Research Group Inc.
Newmarket, Ontario, Canada, L3Y 3R7
Rheumatology Research Associates
Ottawa, Ontario, Canada, K1H1A2
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 258
Canada
Centre de Recherche Saint-Louis
Sainte Foy, Canada, G1W 4R4
Czechia
Revmatologie s.r.o.
Brno, Czechia, 638 00
ARTMEDI UPD s.r.o.
Hostivice, Czechia, 253 01
ARTHROMED s.r.o.
Pardubice, Czechia, 530 02
Affidea Praha s.r.o
Praha 11, Czechia, 148 00
Revmatologicka Ambulance
Praha 4, Czechia, 140 00
Fakultni Thomayerova nemocnice s poliklinikou - Klinicko-farmakologicka jednotka
Praha, Czechia, 140 59
Revmatologicka Ambulance
Sokolov, Czechia, 356 01
PV-Medical s.r.o.
Zlin, Czechia, 760 01
Estonia
Innomedica Medical and Research Centre
Tallinn, Estonia, EE-10117
East Tallinn Central Hospital
Tallinn, Estonia, EE-11412
Clinical Research Centre Ltd
Tartu, Estonia, 50106
Tartu University Hospital
Tartu, Estonia, EE-51014
France
Hopital Ambroise-Pare
Boulogne, France, 92104
Hopital Henri Mondor
Créteil, France, 94010
IPROS - CHR ORLEANS - Hôpital de la Source
Orléans Cedex 2, France, 45067
Hopital Cochin
Paris, France, 75014
Groupe Hospitalier Pitié- Salpétrière
Paris, France, 75651
Germany
Charite - Universitätsmedizin Berlin
Berlin, Germany, 12203
Universitatsklinikum Erlangen
Erlangen, Germany, 91054
Centrum fur innovative Diagnostik und Therapie Rheumatologie Immunologie GmbH
Frankfurt/Main, Germany, 60528
Schön Klink Hamburg-Eilbek
Hamburg, Germany, 22081
Universitatsklinikum Heidelberg
Heidelberg, Germany, 69120
Rheumazentrum Ruhrgebiet
Herne, Germany, 44652
Hungary
Qualiclinic kft
Budapest, Hungary, 1036
Synexus Magyarország Kft.
Budapest, Hungary, 1036
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
Debrecen, Hungary, 4032
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, Hungary, 2143
Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet
Veszprém, Hungary, 8200
Netherlands
Leiden Universitair Medisch Centrum
Leiden, Netherlands, 2333 ZA
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6229 HX
Poland
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
Bialystok, Poland, 15-099
NZOZ Osteo-Medic sc A. Racewicz J. Supronik
Bialystok, Poland, 15-351
Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
Bydgoszcz, Poland, 85-168
Synexus SCM Sp. z o.o.
Gdynia, Poland, 81-384
Niepubliczny Zaklad Opieki Zdrowotnej REUMED
Lublin, Poland, 20-607
Prywatna Praktyka Lekarska Pawel Hrycaj
Poznan, Poland, 61-397
NZOZ NASZ LEKARZ Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna
Torun, Poland, 87-100
Synexus SCM Sp. z o.o.
Wroclaw, Poland, 50-088
Romania
CMI Cristei R. Dorica
Braila, Romania, 810019
Sf. Maria Clinical Hospital
Bucharest, Romania, 011172
Emergency County Clinical Hospital
Cluj-Napoca, Romania, 400006
Sf Apostol Andrei Emergency Clinical County Hospital
Galati, Romania, 800578
C.M.I. Dr. Ciornohuz Adriana
Iasi, Romania, 700127
Russian Federation
Sverdlovsk Regional Clinical Hospital 1
Ekaterinburg, Russian Federation, 620102
Research Medical Complex Vashe Zdorovie
Kazan, Russian Federation, 420103
Kemerovo Regional Clinical Hospital
Kemerovo, Russian Federation, 650066
Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru
Moscow, Russian Federation, 115522
Nizhniy Novgorod State Medical Academy of Roszdrav
Nizhniy Novgorod, Russian Federation, 603005
Departmental Hospital at Smolensk Station RZhD JSC
Smolensk, Russian Federation, 214025
Regional Clinical Hospital
Vladimir, Russian Federation, 600023
Slovakia
Narodny ustav reumatickych chorob
Piestany, Slovakia, 921 12
MU Dr. Zuzana Cizmarikova s.r.o.
Poprad, Slovakia, 058 01
Spain
Hospital Universitario a Coruna
A Coruña, Spain, 15006
Hospital de Bellvitge
Barcelona, Spain, 08907
Hospital Universitario Reina Sofia
Cordoba, Spain, 14001
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Corporacion Sanitaria Parc Tauli
Sabadell, Spain, 08208
Hospital Clinico Universitario de Santiago
Santiago de Compostela, Spain, 15706
Sweden
Skånes Universitetssjukhus- Malmö
Malmö, Sweden, 20502
United Kingdom
Barnsley Hospital
Barnsley South Yorkshire, United Kingdom, S75 2EP
Royal National Hospital for Rheumatic Diseases
Bath, United Kingdom, BA1 1RL
Chapel Allerton Hospital
Leeds, United Kingdom, LS7 4SA
Nuffield Orthopaedic Centre
Oxford, United Kingdom, OX3 7LD
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Lilia Pineda, MD Celgene Corporation

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01583374     History of Changes
Other Study ID Numbers: CC-10004-AS-001
2011-001555-37 ( EudraCT Number )
First Posted: April 24, 2012    Key Record Dates
Results First Posted: March 17, 2015
Last Update Posted: September 12, 2018
Last Verified: September 2018

Keywords provided by Celgene:
spondylitis
spondyloarthritis
Spondyloarthropathy
Oral preparation

Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Spondylarthritis
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Ankylosis
Joint Diseases
Arthritis
Apremilast
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances