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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01583374
First received: April 20, 2012
Last updated: April 27, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
Ankylosing Spondyloarthritis
Drug: Apremilast tablet 20 mg
Drug: Apremilast tablet 30 mg BID
Drug: 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 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 490
Study Start Date: June 2012
Estimated Study Completion Date: December 2018
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  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: NCT01583374

  Show 98 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Lilia Pineda, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01583374     History of Changes
Other Study ID Numbers: CC-10004-AS-001, 2011-001555-37
Study First Received: April 20, 2012
Results First Received: February 24, 2015
Last Updated: April 27, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Estonia: The State Agency of Medicine
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Netherlands: Medicines Evaluation Board (MEB)
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
spondylitis
spondyloarthritis
Spondyloarthropathy
Oral preparation

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

ClinicalTrials.gov processed this record on July 30, 2015