Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

NCT ID: NCT01172938

Last Updated: 2020-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 504 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-02
• Study Completion Date: 2016-10-27

Brief Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis, specifically in improving signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.

Detailed Description

Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.

Conditions

Psoriatic Arthritis

Study Design

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

Study Groups

Apremilast 20 mg

20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase

Group Type: EXPERIMENTAL

Apremilast 20mg

Intervention Type: DRUG

Apremilast 20 mg twice daily, orally

Apremilast 30mg

30 mg Apremilast tablets administered twice a day for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice a day for up to 4.5 years in the active treatment / long-term safety phase orally twice daily

Group Type: EXPERIMENTAL

Apremilast 30mg

Intervention Type: DRUG

Apremilast 30 mg twice daily, orally

Placebo + 20 mg Apremilast

Placebo + 20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 20 mg Apremilast twice daily at Week 16

Group Type: PLACEBO_COMPARATOR

Placebo + 20 mg Apremilast

Intervention Type: DRUG

Placebo + 20 mg Apremilast

Placebo + 30 mg Apremilast

Placebo + 30 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 30 mg Apremilast twice daily at Week 16.

Group Type: PLACEBO_COMPARATOR

Placebo + 30 mg Apremilast

Intervention Type: DRUG

Placebo + 30 mg Apremilast

Interventions

Apremilast 20mg

Apremilast 20 mg twice daily, orally

Intervention Type: DRUG

Apremilast 30mg

Apremilast 30 mg twice daily, orally

Intervention Type: DRUG

Placebo + 20 mg Apremilast

Placebo + 20 mg Apremilast

Intervention Type: DRUG

Placebo + 30 mg Apremilast

Placebo + 30 mg Apremilast

Intervention Type: DRUG

Other Intervention Names

CC-10004; CC-10004; Placebo; CC-10004; Placebo; CC-10004

Eligibility Criteria

Inclusion Criteria

• Males or females, aged ≥ 18 years at time of consent.
• Have a diagnosis of Psoriatic Arthritis (PSA, by any criteria) of ≥ 6 months duration.
• Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) at time of screening.
• Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)
• May not have axial involvement alone
• Concurrent treatment allowed with methotrexate, leflunomide, or sulfasalazine
• Have ≥ 3 swollen AND ≥ 3 tender joints.
• Males & Females must use contraception
• Stable dose of nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics and low dose oral corticosteroids allowed.

Exclusion Criteria

• Pregnant or breast feeding.
• History of allergy to any component of the investigational product.
• Hepatitis B surface antigen and/or Hepatitis C antibody positive at screening.
• Therapeutic failure on > 3 agents for PsA or > 1 biologic tumor necrosis factor (TNF) blocker

• 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

Achieve Clinical Research LLC

Birmingham, Alabama, United States

Arizona Research Center

Phoenix, Arizona, United States

UCSD-Thornton Hospital

La Jolla, California, United States

Stanford University Medical Center

Palo Alto, California, United States

Inland Rheumatology Clinical Trials

Upland, California, United States

Arthritis and Rheumatic Disease Specialties

Aventura, Florida, United States

North Florida Dermatology

Jacksonville, Florida, United States

Tampa Medical Group Pa

Tampa, Florida, United States

Sonora Clinical Research, LLC

Boise, Idaho, United States

Coeur D'Alene Arthritis Clinic

Coeur d'Alene, Idaho, United States

The Arthritis Center

Springfield, Illinois, United States

St. Francis Hospital and Health Centers

Michigan City, Indiana, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Justus Fiechtner MD PC

Lansing, Michigan, United States

Physicians East

Greenville, North Carolina, United States

Carolina Bone and Joint

Monroe, North Carolina, United States

Piedmont Medical Research Associates Inc

Winston-Salem, North Carolina, United States

Health Research of Oklahoma

Oklahoma City, Oklahoma, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Clinical Research Center of Reading, LLP

West Reading, Pennsylvania, United States

Dermatology Treatment and Research Center

Dallas, Texas, United States

Accurate Clinical Research Inc

Houston, Texas, United States

Arthritis and Osteoporosis Associates LLP

Lubbock, Texas, United States

Center for Clinical Studies

Webster, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Seattle Rheumatology Associates

Seattle, Washington, United States

Arthritis Northwest Rheumatology

Spokane, Washington, United States

Monash Medical Centre

Clayton, Victoria, Australia

Eastern Health Clinical School

Box Hill, , Australia

Repatriation General Hospital

Daws Park, , Australia

St Vincent's Hospital Melbourne

Fitzroy, , Australia

Emeritus Research

Malvern, , Australia

Ordination Wien Dr. Hanusch

Vienna, , Austria

Medizinische Universitat Wien

Vienna, , Austria

Kaiser-Franz-Josef Spital

Vienna, , Austria

Nexus Clinical Research

St. John's, Newfoundland and Labrador, Canada

St. Clare's Health Care Corporation of St. John's

St. John's, Newfoundland and Labrador, Canada

Ultranova Skincare

Barrie, Ontario, Canada

MAC Research Incorporated

Hamilton, Ontario, Canada

K-W Musculoskeletal Research Inc.

Kitchener, Ontario, Canada

Saint Josephs Healthcare System

London, Ontario, Canada

Credit Valley Professional Building

Mississauga, Ontario, Canada

The Arthritis Program Research Group Inc.

Newmarket, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

Probity Medical Research Inc

Waterloo, Ontario, Canada

Jude Rodrigues Private Practice

Windsor, Ontario, Canada

Hospital Maisonneuve - Rosemont

Montreal, Quebec, Canada

Institut de Rhumatologie de Montreal

Montreal, Quebec, Canada

Centre de Rhumatologie St-Louis

Sainte-Foy, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke-Hospital Fleurimont

Sherbrooke, Quebec, Canada

Saskatoon Osteoporosis Centre

Saskatoon, Saskatchewan, Canada

Ipros - Chr Orleans

Orléans, , France

Hopital Purpan

Toulouse, , France

Klinikum Duisburg, Wedau Kliniken

Duisburg, , Germany

Friedrich-Alexander-Universiät Erlangen Nürnberg

Erlangen, , Germany

Allgemeines Krankenhaus Eilbeck

Hamburg, , Germany

Rheumazentrum Ruhrgebiet

Herne, , Germany

Praxis Prof. Herbert Kellner

München, , Germany

Qualiclinic kft

Budapest, , Hungary

Synexus Magyarország Kft.

Budapest, , Hungary

Honvéd Kórház - Állami Egészségügyi Központ

Budapest, , Hungary

MAV Korhaz es Rendelointezet Szolnok

Szolnok, , Hungary

Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet

Veszprém, , Hungary

P3 Research

Crofton Downs, , New Zealand

Waikato hospital

Hamilton, , New Zealand

Middlemore Clinical Trials

New Zealand, , New Zealand

Queen Elizabeth Hospital for Rheumatic Disease

Rotorua, , New Zealand

North Shore Hospital

Takapuna, , New Zealand

Timaru Hospital

Timaru, , New Zealand

Szpital Uniwersytecki im. Dr A.Jurasza

Bydgoszcz, , Poland

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Synexus SCM Sp. z o.o.

Gdynia, , Poland

Synexus SCM Sp. z o.o.

Katowice, , Poland

Wojewodzki Zespol Reumatologiczny

Sopot, , Poland

Synexus SCM Sp. z o.o. Oddz. Warszawa

Warsaw, , Poland

Kemerovo State Medical Academy

Kemerovo, , Russia

Ryazan I.P. Pavlov State Medical University

Ryazan, , Russia

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, , Russia

Regional Clinical Hospital

Vladimir, , Russia

Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy

Voronezh, , Russia

Panorama Medical Centre

Cape Town, , South Africa

Groote Schuur Hospital

Cape Town, , South Africa

Chelmsford Medical Centre 2

Durban, , South Africa

Clinresco Centres Pty Ltd

Johannesburg, , South Africa

The Park

Pinelands, , South Africa

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, , Spain

Barnsley Hospital

Barnsley South Yorkshire, , United Kingdom

Colchester General Hospital

Colchester, , United Kingdom

West Suffolk Hospital

Edmunds, , United Kingdom

Countries

United States; Australia; Austria; Canada; France; Germany; Hungary; New Zealand; Poland; Russia; South Africa; Spain; United Kingdom

References

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Reference Type: RESULT

PMID: 25593233 (View on PubMed)

Mease PJ, Hatemi G, Paris M, Cheng S, Maes P, Zhang W, Shi R, Flower A, Picard H, Stein Gold L. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behcet's Syndrome. Am J Clin Dermatol. 2023 Sep;24(5):809-820. doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.

Reference Type: DERIVED

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Mease PJ, Gladman DD, Kavanaugh A, McGonagle D, Nash P, Guerette B, Nakasato P, Brunori M, Teng L, McInnes IB. Articular and Extra-Articular Benefits in ACR20 Non-responders at Week 104 Treated With Apremilast: Pooled Analysis of Three Randomized Controlled Trials. Rheumatol Ther. 2021 Dec;8(4):1677-1691. doi: 10.1007/s40744-021-00369-x. Epub 2021 Sep 18.

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Mease PJ, Gladman DD, Ogdie A, Coates LC, Behrens F, Kavanaugh A, McInnes I, Queiro R, Guerette B, Brunori M, Teng L, Smolen JS. Treatment-to-Target With Apremilast in Psoriatic Arthritis: The Probability of Achieving Targets and Comprehensive Control of Disease Manifestations. Arthritis Care Res (Hoboken). 2020 Jun;72(6):814-821. doi: 10.1002/acr.24134. Epub 2020 May 8.

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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: DERIVED

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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: DERIVED

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Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, Lespessailles E, Hall S, Hochfeld M, Hu C, Hough D, Stevens RM, Schett G. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014 Jun;73(6):1020-6. doi: 10.1136/annrheumdis-2013-205056. Epub 2014 Mar 4.

Reference Type: DERIVED

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Other Identifiers

CC-10004-PSA-002

Identifier Type: -

Identifier Source: org_study_id