Clinical trial NCT01583374: Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondyloarthritis
Keywords: spondylitis
spondyloarthritis
Spondyloarthropathy
Oral preparation
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-04-24
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 were randomized in a 1:1:1 ratio to placebo, apremilast 20 mg BID and apremilast 30 mg BID. The duration of the study was approximately 5 years. The double blind period (when patients nor the physician knew whether placebo or apremilast was taken) was 24 weeks. At Week 16, participants who did 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 were entered in "early escape" from their current treatment in a double-blinded manner. However, such participants were permitted to continue in the study. At Week 24, participants may have entered 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 participants transitioned to receive double-blinded apremilast 30 mg BID and remained on double-blinded apremilast 30 mg BID because they continued 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 participants continued on either double-blinded apremilast 20 mg BID or 30 mg BID treatment. After all participants had completed Week 52 or had terminated early from the study and the 52-week data base was locked, apremilast 20 mg BID or 30 mg BID treatment was provided.

Eligibility criteria: Inclusion Criteria:

* Must have a documented diagnosis of ankylosing spondylitis as defined by low back pain and stiffness, which improves with exercise, but is not relieved by rest for more than 3 months prior to screening. At the completion of screening procedures, a documented diagnosis of definite active AS, as defined by the modified New York criteria (1984) whereby both criteria, at least 1 radiographic criterion and at least 1 clinical criterion, must be met
* 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

Primary outcomes:
measure: Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) Response at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS) Response at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Ankylosing Spondylitis Quality of Life (ASQoL) Summary Score at Week 24
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Baseline and Week 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index-Linear (BASMI-Linear) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 104 and Week 260
timeFrame: Baseline to Week 104 and 260
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase
timeFrame: From Week 0 to Week 24; the median duration of exposure was 23.57 weeks for the placebo arm, 23.71 weeks for the apremilast 20 mg arm and 24.00 weeks for the apremilast 30 mg arm.
measure: Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period
timeFrame: Week 0 to week 260; overall mean duration of exposure to apremilast 20 mg and 30 mg BID was 160.96 weeks
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Sun Valley Arthritis Center
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: San Francisco
country: United States
facility: UCSF Arthritis Center
state: California
city: Pinellas Park
country: United States
facility: Advent Clinical Research Centers, Inc
state: Florida
city: Tampa
country: United States
facility: Burnette & Silverfield, MDS PLC
state: Florida
city: Vero Beach
country: United States
facility: Alastair Kennedy, MD Research
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Cumberland
country: United States
facility: Klein and Associates MD, PA
state: Maryland
city: Hagerstown
country: United States
facility: Klein and Associates MD, PA
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Eagan
country: United States
facility: Saint Paul Rheumatology, PA
state: Minnesota
city: Cleveland
country: United States
facility: MetroHealth Medical Systems
state: Ohio
city: Dayton
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Jackson
country: United States
facility: The Arthritis Clinic
state: Tennessee
city: Memphis
country: United States
facility: Ramesh C Gupta MD
state: Tennessee
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Franklin
country: United States
facility: Rheumatology and Immunotherapy Center
state: Wisconsin
city: Hobart
country: Australia
facility: Southern Clinical Research
state: Tasmania
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Maroochydore
country: Australia
facility: Coastal Joint Care
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
city: Wien
country: Austria
facility: Krankenhaus Wien-Hietzing
city: Pleven
country: Bulgaria
facility: Diagnostic and Consulting Center Sv. Pantaleymon
city: Sofia
country: Bulgaria
facility: National Multiprofile Transport Hospital Tzar Boris III
city: Sofia
country: Bulgaria
facility: 17 Diagnostic and Consulting Centre
city: Sofia
country: Bulgaria
facility: Military Medical Academy - MHAT
city: Varna
country: Bulgaria
facility: Diagnostic Consulting Center N4
city: Calgary
country: Canada
facility: Clinic: University of Calgary Heritage Medical Research Clinic (HMRC),Teaching Research and Wellness (TRW)
state: Alberta
city: St John's
country: Canada
facility: Nexus Clinical Research
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Cividino Medicine Professional Corporation
state: Ontario
city: Hamilton
country: Canada
facility: Dr. William G. Bensen Medicine Professional Corporation
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Professional Building
state: Ontario
city: Newmarket
country: Canada
facility: The Arthritis Program Research Group Inc.
state: Ontario
city: Ottawa
country: Canada
facility: Rheumatology Research Associates
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Saint-Louis
country: Canada
facility: Centre de Recherche Saint-Louis
state: Quebec
city: Brno
country: Czechia
facility: Revmatologie s.r.o.
city: Hostivice
country: Czechia
facility: ARTMEDI UPD s.r.o.
city: Pardubice
country: Czechia
facility: ARTHROMED s.r.o.
city: Praha 11
country: Czechia
facility: Medifin a.s, Šustova
city: Praha 4
country: Czechia
facility: Revmatologicka Ambulance
city: Praha
country: Czechia
facility: Fakultni Thomayerova nemocnice s poliklinikou - Klinicko-farmakologicka jednotka
city: Sokolov
country: Czechia
facility: Revmatologicka Ambulance
city: Zlin
country: Czechia
facility: PV-Medical s.r.o.
city: Tallinn
country: Estonia
facility: Innomedica Medical and Research Centre
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Clinical Research Centre Ltd
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Boulogne
country: France
facility: Hopital Ambroise-Pare
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Orléans Cedex 2
country: France
facility: IPROS - CHR ORLEANS - Hôpital de la Source
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Groupe Hospitalier Pitié- Salpétrière
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Frankfurt
country: Germany
facility: Centrum fur innovative Diagnostik und Therapie Rheumatologie Immunologie GmbH
city: Hamburg
country: Germany
facility: Schön Klink Hamburg-Eilbek
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Budapest
country: Hungary
facility: Qualiclinic kft
city: Budapest
country: Hungary
facility: Synexus Magyarország Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Veszprém
country: Hungary
facility: Veszprem Megyei Csolnoky Ferenc Korhaz-Rendelointezet
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Bialystok
country: Poland
facility: Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
city: Bialystok
country: Poland
facility: NZOZ Osteo-Medic sc A. Racewicz J. Supronik
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Gdynia
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Pawel Hrycaj
city: Torun
country: Poland
facility: NZOZ NASZ LEKARZ Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna
city: Wroclaw
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Braila
country: Romania
facility: Cristei R. Rodica - Private Medical Practice
city: Bucharest
country: Romania
facility: Sf. Maria Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Emergency County Clinical Hospital
city: Galati
country: Romania
facility: Sf Apostol Andrei Emergency Clinical County Hospital
city: Iasi
country: Romania
facility: RK Medcenter SRL
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital 1
city: Kazan
country: Russian Federation
facility: Research Medical Complex Vashe Zdorovie
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "Rheumatology Research Institute RAMS"
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod State Medical Academy of Roszdrav
city: Smolensk
country: Russian Federation
facility: Departmental Hospital at Smolensk Station RZhD JSC
city: Vladimir
country: Russian Federation
facility: Regional Clinical Hospital
city: Piestany
country: Slovakia
facility: Narodny ustav reumatickych chorob
city: Poprad
country: Slovakia
facility: MUDr. Zuzana Cizmarikova, s.r.o., Reumatologick ambulancia
city: A Coruña
country: Spain
facility: Hospital Universitario a Coruna
city: Barcelona
country: Spain
facility: Hospital de Bellvitge
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli de Sabadell
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela Travesía de la Choupana s/n
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus- Malmö
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital
city: Bath
country: United Kingdom
facility: Royal National Hospital for Rheumatic Diseases
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: Oxford
country: United Kingdom
facility: Nuffield Orthopaedic Centre
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Gladman DD, Kavanaugh A, Gomez-Reino JJ, Wollenhaupt J, Cutolo M, Schett G, Lespessailles E, Guerette B, Delev N, Teng L, Edwards CJ, Birbara CA, Mease PJ. Therapeutic benefit of apremilast on enthesitis and dactylitis in patients with psoriatic arthritis: a pooled analysis of the PALACE 1-3 studies. RMD Open. 2018 Jun 27;4(1):e000669. doi: 10.1136/rmdopen-2018-000669. eCollection 2018.
citation: Kavanaugh A, Gladman DD, Edwards CJ, Schett G, Guerette B, Delev N, Teng L, Paris M, Mease PJ. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019 May 10;21(1):118. doi: 10.1186/s13075-019-1901-3.
citation: Taylor PC, van der Heijde D, Landewe R, McCue S, Cheng S, Boonen A. A Phase III Randomized Study of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Active Ankylosing Spondylitis. J Rheumatol. 2021 Aug;48(8):1259-1267. doi: 10.3899/jrheum.201088. Epub 2021 Feb 15.