Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis

NCT ID: NCT01583374

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 490 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-02
• Study Completion Date: 2018-10-25

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.

Conditions

Ankylosing Spondyloarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Apremilast 20 mg

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

Group Type: EXPERIMENTAL

Apremilast tablet 20 mg

Intervention Type: DRUG

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

Apremilast 30 mg

Apremilast 30 mg was taken orally twice a day

Group Type: EXPERIMENTAL

Apremilast tablet 30 mg BID

Intervention Type: DRUG

Apremilast 30 mg was taken orally twice a day

Placebo

Identically matched placebo tablets were taken orally twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Apremilast tablet 20 mg

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

Intervention Type: DRUG

Apremilast tablet 30 mg BID

Apremilast 30 mg was taken orally twice a day

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Otezla; CC-10004; Otezla; CC-10004

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Sun Valley Arthritis Center

Peoria, Arizona, United States

University of California, San Diego

La Jolla, California, United States

Desert Medical Advances

Palm Desert, California, United States

UCSF Arthritis Center

San Francisco, California, United States

Advent Clinical Research Centers, Inc

Pinellas Park, Florida, United States

Burnette & Silverfield, MDS PLC

Tampa, Florida, United States

Alastair Kennedy, MD Research

Vero Beach, Florida, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Klein and Associates MD, PA

Cumberland, Maryland, United States

Klein and Associates MD, PA

Hagerstown, Maryland, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Saint Paul Rheumatology, PA

Eagan, Minnesota, United States

MetroHealth Medical Systems

Cleveland, Ohio, United States

STAT Research, Inc.

Dayton, Ohio, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

The Arthritis Clinic

Jackson, Tennessee, United States

Ramesh C Gupta MD

Memphis, Tennessee, United States

Austin Regional Clinic

Austin, Texas, United States

University of Utah Hospitals and Clinics

Salt Lake City, Utah, United States

Rheumatology and Immunotherapy Center

Franklin, Wisconsin, United States

Southern Clinical Research

Hobart, Tasmania, Australia

Emeritus Research

Camberwell, Victoria, Australia

Coastal Joint Care

Maroochydore, , Australia

Royal Perth Hospital

Perth, , Australia

The Queen Elizabeth Hospital

Woodville South, , Australia

Krankenhaus Wien-Hietzing

Vienna, , Austria

Diagnostic and Consulting Center Sv. Pantaleymon

Pleven, , Bulgaria

National Multiprofile Transport Hospital Tzar Boris III

Sofia, , Bulgaria

17 Diagnostic and Consulting Centre

Sofia, , Bulgaria

Military Medical Academy - MHAT

Sofia, , Bulgaria

Diagnostic Consulting Center N4

Varna, , Bulgaria

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

Calgary, Alberta, Canada

Nexus Clinical Research

St. John's, Newfoundland and Labrador, Canada

Cividino Medicine Professional Corporation

Hamilton, Ontario, Canada

Dr. William G. Bensen Medicine Professional Corporation

Hamilton, Ontario, Canada

Credit Valley Professional Building

Mississauga, Ontario, Canada

The Arthritis Program Research Group Inc.

Newmarket, Ontario, Canada

Rheumatology Research Associates

Ottawa, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

Centre de Recherche Saint-Louis

Saint-Louis, Quebec, Canada

Revmatologie s.r.o.

Brno, , Czechia

ARTMEDI UPD s.r.o.

Hostivice, , Czechia

ARTHROMED s.r.o.

Pardubice, , Czechia

Revmatologicka Ambulance

Prague, , Czechia

Fakultni Thomayerova nemocnice s poliklinikou - Klinicko-farmakologicka jednotka

Prague, , Czechia

Medifin a.s, Šustova

Prague, , Czechia

Revmatologicka Ambulance

Sokolov, , Czechia

PV-Medical s.r.o.

Zlín, , Czechia

Innomedica Medical and Research Centre

Tallinn, , Estonia

East Tallinn Central Hospital

Tallinn, , Estonia

Clinical Research Centre Ltd

Tartu, , Estonia

Tartu University Hospital

Tartu, , Estonia

Hopital Ambroise-Pare

Boulogne, , France

Hopital Henri Mondor

Créteil, , France

IPROS - CHR ORLEANS - Hôpital de la Source

Orléans, , France

Hopital Cochin

Paris, , France

Groupe Hospitalier Pitié- Salpétrière

Paris, , France

Charite - Universitätsmedizin Berlin

Berlin, , Germany

Universitatsklinikum Erlangen

Erlangen, , Germany

Centrum fur innovative Diagnostik und Therapie Rheumatologie Immunologie GmbH

Frankfurt, , Germany

Schön Klink Hamburg-Eilbek

Hamburg, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Rheumazentrum Ruhrgebiet

Herne, , Germany

Qualiclinic kft

Budapest, , Hungary

Synexus Magyarország Kft.

Budapest, , Hungary

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, , Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Veszprem Megyei Csolnoky Ferenc Korhaz-Rendelointezet

Veszprém, , Hungary

Leiden Universitair Medisch Centrum

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk

Bialystok, , Poland

NZOZ Osteo-Medic sc A. Racewicz J. Supronik

Bialystok, , Poland

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Synexus SCM Sp. z o.o.

Gdynia, , Poland

Zespol Poradni Specjalistycznych

Lublin, , Poland

Prywatna Praktyka Lekarska Pawel Hrycaj

Poznan, , Poland

NZOZ NASZ LEKARZ Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna

Torun, , Poland

Synexus SCM Sp. z o.o.

Wroclaw, , Poland

Cristei R. Rodica - Private Medical Practice

Brăila, , Romania

Sf. Maria Clinical Hospital

Bucharest, , Romania

Emergency County Clinical Hospital

Cluj-Napoca, , Romania

Sf Apostol Andrei Emergency Clinical County Hospital

Galati, , Romania

RK Medcenter SRL

Iași, , Romania

Research Medical Complex Vashe Zdorovie

Kazan', , Russia

Kemerovo Regional Clinical Hospital

Kemerovo, , Russia

Federal State Budget Institution "Rheumatology Research Institute RAMS"

Moscow, , Russia

Nizhniy Novgorod State Medical Academy of Roszdrav

Nizhny Novgorod, , Russia

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, , Russia

Regional Clinical Hospital

Vladimir, , Russia

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, , Russia

Narodny ustav reumatickych chorob

Piešťany, , Slovakia

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

Poprad, , Slovakia

Hospital Universitario a Coruna

A Coruña, , Spain

Hospital de Bellvitge

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Corporacio Sanitaria Parc Tauli de Sabadell

Sabadell, , Spain

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

Santiago de Compostela, , Spain

Skånes Universitetssjukhus- Malmö

Malmo, , Sweden

Barnsley Hospital

Barnsley, , United Kingdom

Royal National Hospital for Rheumatic Diseases

Bath, , United Kingdom

Chapel Allerton Hospital

Leeds, , United Kingdom

Nuffield Orthopaedic Centre

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Bulgaria; Canada; Czechia; Estonia; France; Germany; Hungary; Netherlands; Poland; Romania; Russia; Slovakia; Spain; Sweden; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30018799 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31077258 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33589554 (View on PubMed)

Other Identifiers

2011-001555-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-10004-AS-001

Identifier Type: -

Identifier Source: org_study_id