Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis

NCT01583374 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-10004-AS-0012011-001555-37
• Study Type: interventional
• Target: 490
• Locations: 16 countries
• Sites: 94

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.

Conditions

Ankylosing Spondyloarthritis

Keywords

spondylitis; spondyloarthritis; Spondyloarthropathy; Oral preparation

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) Response at Week 16

  ASAS 20 was 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)

  Baseline and Week 16

Secondary Outcomes (9)

• Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24

  Baseline and Week 24

• Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

  Baseline and Week 24

• Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS) Response at Week 24

  Baseline and Week 24

• Change From Baseline in the Ankylosing Spondylitis Quality of Life (ASQoL) Summary Score at Week 24

  Baseline and Week 24

• 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

  Baseline and Week 24

Study Arms (3)

Apremilast 20 mg

EXPERIMENTAL

Apremilast 20 mg was taken orally twice a day (BID)

Drug: Apremilast tablet 20 mg

Apremilast 30 mg

EXPERIMENTAL

Apremilast 30 mg was taken orally twice a day

Drug: Apremilast tablet 30 mg BID

Placebo

PLACEBO COMPARATOR

Identically matched placebo tablets were taken orally twice a day

Drug: Placebo

Interventions

Apremilast tablet 20 mg DRUG

Apremilast 20 mg was taken orally twice a day (BID)

Also known as: Otezla; CC-10004

Apremilast 20 mg

Apremilast tablet 30 mg BID DRUG

Apremilast 30 mg was taken orally twice a day

Also known as: Otezla; CC-10004

Apremilast 30 mg

Placebo DRUG

Identically matched placebo tablets were taken orally twice a day during the placebo controlled phase.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- Prior treatment with a Tumor Necrosis Factor (TNF) blocker and any biologic treatment for AS

Sponsors & Collaborators

• Amgen: lead

Study Sites (103)

Sun Valley Arthritis Center

Peoria, Arizona, 85381, United States

Location

University of California, San Diego

La Jolla, California, 92093-0943, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

UCSF Arthritis Center

San Francisco, California, 94143-0326, United States

Location

Advent Clinical Research Centers, Inc

Pinellas Park, Florida, 33781, United States

Location

Burnette & Silverfield, MDS PLC

Tampa, Florida, 33614, United States

Location

Alastair Kennedy, MD Research

Vero Beach, Florida, 32960, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Klein and Associates MD, PA

Cumberland, Maryland, 21502, United States

Location

Klein and Associates MD, PA

Hagerstown, Maryland, 21740, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01605, United States

Location

Saint Paul Rheumatology, PA

Eagan, Minnesota, 55121, United States

Location

MetroHealth Medical Systems

Cleveland, Ohio, 44109, United States

Location

STAT Research, Inc.

Dayton, Ohio, 45417, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

The Arthritis Clinic

Jackson, Tennessee, 38305, United States

Location

Ramesh C Gupta MD

Memphis, Tennessee, 38119, United States

Location

Austin Regional Clinic

Austin, Texas, 78731, United States

Location

University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States

Location

Rheumatology and Immunotherapy Center

Franklin, Wisconsin, 53132, United States

Location

Southern Clinical Research

Hobart, Tasmania, 7000, Australia

Location

Emeritus Research

Camberwell, Victoria, 3124, Australia

Location

Coastal Joint Care

Maroochydore, 4558, Australia

Location

Royal Perth Hospital

Perth, 6849, Australia

Location

The Queen Elizabeth Hospital

Woodville South, 5011, Australia

Location

Krankenhaus Wien-Hietzing

Vienna, 1130, Austria

Location

Diagnostic and Consulting Center Sv. Pantaleymon

Pleven, 5800, Bulgaria

Location

National Multiprofile Transport Hospital Tzar Boris III

Sofia, 1233, Bulgaria

Location

17 Diagnostic and Consulting Centre

Sofia, 1505, Bulgaria

Location

Military Medical Academy - MHAT

Sofia, 1606, Bulgaria

Location

Diagnostic Consulting Center N4

Varna, 9010, Bulgaria

Location

Clinic: University of Calgary Heritage Medical Research Clinic (HMRC),Teaching Research and Wellness (TRW)

Calgary, Alberta, T2N 4Z6, Canada

Location

Nexus Clinical Research

St. John's, Newfoundland and Labrador, A1A 5EB, Canada

Location

Cividino Medicine Professional Corporation

Hamilton, Ontario, L8N 2B6, Canada

Location

Dr. William G. Bensen Medicine Professional Corporation

Hamilton, Ontario, L8N1Y2, Canada

Location

Credit Valley Professional Building

Mississauga, Ontario, L5M 2V8, Canada

Location

The Arthritis Program Research Group Inc.

Newmarket, Ontario, L3Y 3R7, Canada

Location

Rheumatology Research Associates

Ottawa, Ontario, K1H1A2, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 258, Canada

Location

Centre de Recherche Saint-Louis

Saint-Louis, Quebec, G1W 4R4, Canada

Location

Revmatologie s.r.o.

Brno, 638 00, Czechia

Location

ARTMEDI UPD s.r.o.

Hostivice, 253 01, Czechia

Location

ARTHROMED s.r.o.

Pardubice, 530 02, Czechia

Location

Revmatologicka Ambulance

Prague, 140 00, Czechia

Location

Fakultni Thomayerova nemocnice s poliklinikou - Klinicko-farmakologicka jednotka

Prague, 140 59, Czechia

Location

Medifin a.s, Šustova

Prague, 148 00, Czechia

Location

Revmatologicka Ambulance

Sokolov, 356 01, Czechia

Location

PV-Medical s.r.o.

Zlín, 760 01, Czechia

Location

Innomedica Medical and Research Centre

Tallinn, 10117, Estonia

Location

East Tallinn Central Hospital

Tallinn, 11412, Estonia

Location

Clinical Research Centre Ltd

Tartu, 50106, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Hopital Ambroise-Pare

Boulogne, 92100, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

IPROS - CHR ORLEANS - Hôpital de la Source

Orléans, 45067, France

Location

Hopital Cochin

Paris, 75014, France

Location

Groupe Hospitalier Pitié- Salpétrière

Paris, 75651, France

Location

Charite - Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

Universitatsklinikum Erlangen

Erlangen, 91054, Germany

Location

Centrum fur innovative Diagnostik und Therapie Rheumatologie Immunologie GmbH

Frankfurt, 60528, Germany

Location

Schön Klink Hamburg-Eilbek

Hamburg, 22081, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Rheumazentrum Ruhrgebiet

Herne, 44649, Germany

Location

Qualiclinic kft

Budapest, 1036, Hungary

Location

Synexus Magyarország Kft.

Budapest, 1036, Hungary

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Veszprem Megyei Csolnoky Ferenc Korhaz-Rendelointezet

Veszprém, 8200, Hungary

Location

Leiden Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6229 HX, Netherlands

Location

Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk

Bialystok, 15-099, Poland

Location

NZOZ Osteo-Medic sc A. Racewicz J. Supronik

Bialystok, 15-351, Poland

Location

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Synexus SCM Sp. z o.o.

Gdynia, 81-537, Poland

Location

Zespol Poradni Specjalistycznych

Lublin, 20-582, Poland

Location

Prywatna Praktyka Lekarska Pawel Hrycaj

Poznan, 61-397, Poland

Location

NZOZ NASZ LEKARZ Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna

Torun, 87-100, Poland

Location

Synexus SCM Sp. z o.o.

Wroclaw, 50-088, Poland

Location

Cristei R. Rodica - Private Medical Practice

Brăila, 810019, Romania

Location

Sf. Maria Clinical Hospital

Bucharest, 011172, Romania

Location

Emergency County Clinical Hospital

Cluj-Napoca, 400006, Romania

Location

Sf Apostol Andrei Emergency Clinical County Hospital

Galati, 800578, Romania

Location

RK Medcenter SRL

Iași, 700127, Romania

Location

Research Medical Complex Vashe Zdorovie

Kazan', 420103, Russia

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650066, Russia

Location

Federal State Budget Institution "Rheumatology Research Institute RAMS"

Moscow, 115522, Russia

Location

Nizhniy Novgorod State Medical Academy of Roszdrav

Nizhny Novgorod, 603005, Russia

Location

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, 214025, Russia

Location

Regional Clinical Hospital

Vladimir, 600023, Russia

Location

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, 620102, Russia

Location

Narodny ustav reumatickych chorob

Piešťany, 921 12, Slovakia

Location

MUDr. Zuzana Cizmarikova, s.r.o., Reumatologick ambulancia

Poprad, 058 01, Slovakia

Location

Hospital Universitario a Coruna

A Coruña, 15006, Spain

Location

Hospital de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14001, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Corporacio Sanitaria Parc Tauli de Sabadell

Sabadell, 08208, Spain

Location

Complejo Hospitalario Universitario de Santiago de Compostela Travesía de la Choupana s/n

Santiago de Compostela, 15706, Spain

Location

Skånes Universitetssjukhus- Malmö

Malmo, 20502, Sweden

Location

Barnsley Hospital

Barnsley, S75 2EP, United Kingdom

Location

Royal National Hospital for Rheumatic Diseases

Bath, BA1 1RL, United Kingdom

Location

Chapel Allerton Hospital

Leeds, LS7 4SA, United Kingdom

Location

Nuffield Orthopaedic Centre

Oxford, OX3 7LD, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 30018799 BACKGROUND

• 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.

  PMID: 31077258 BACKGROUND

• 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.

  PMID: 33589554 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing; Spondylitis; Spondylarthritis; Spondylarthropathies

Interventions

apremilast; BID protein, human

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Bone Diseases, Infectious; Infections

Results Point of Contact

• Title: Anne McClain, Senior Study Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2012
• First Posted: April 24, 2012
• Study Start: May 2, 2012
• Primary Completion: February 24, 2014
• Study Completion: October 25, 2018
• Last Updated: May 12, 2020
• Results First Posted: March 17, 2015

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (20); CZ (8); ES (6); NL (2); BU (5); FR (5); RU (7); SL (2); AU (1); GB (4); HU (5); SE (1); PL (8); DE (6); CA (9); RO (5)