Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

NCT01172938 | Completed Phase 3 Results DMC

• 1 other identifier: CC-10004-PSA-002
• Study Type: interventional
• Target: 504
• Locations: 12 countries
• Sites: 89

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.

Conditions

Psoriatic Arthritis

Keywords

Psoriatic Arthritis; Psoriasis; Arthritis; inflammation; skin condition; inflammatory cells; apremilast; CC-10004; phosphodiesterase type 4

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16

  Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.

  Baseline and Week 16

Secondary Outcomes (52)

• Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16

  Baseline and Week 16

• Percentage of Participants With an ACR 20 Response at Week 24

  Baseline and Week 24

• Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24

  Baseline and Week 24

• Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

  Baseline and Week 16

• Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

  Baseline and Week 16

Study Arms (4)

Apremilast 20 mg

EXPERIMENTAL

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

Drug: Apremilast 20mg

Apremilast 30mg

EXPERIMENTAL

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

Drug: Apremilast 30mg

Placebo + 20 mg Apremilast

PLACEBO COMPARATOR

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

Drug: Placebo + 20 mg Apremilast

Placebo + 30 mg Apremilast

PLACEBO COMPARATOR

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.

Drug: Placebo + 30 mg Apremilast

Interventions

Apremilast 20mg DRUG

Apremilast 20 mg twice daily, orally

Also known as: CC-10004

Apremilast 20 mg

Apremilast 30mg DRUG

Apremilast 30 mg twice daily, orally

Also known as: CC-10004

Apremilast 30mg

Placebo + 20 mg Apremilast DRUG

Placebo + 20 mg Apremilast

Also known as: Placebo, CC-10004

Placebo + 20 mg Apremilast

Placebo + 30 mg Apremilast DRUG

Placebo + 30 mg Apremilast

Also known as: Placebo, CC-10004

Placebo + 30 mg Apremilast

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (92)

Achieve Clinical Research LLC

Birmingham, Alabama, 35216, United States

Location

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

UCSD-Thornton Hospital

La Jolla, California, 92093-0943, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304-1808, United States

Location

Inland Rheumatology Clinical Trials

Upland, California, 91786, United States

Location

Arthritis and Rheumatic Disease Specialties

Aventura, Florida, 33180, United States

Location

North Florida Dermatology

Jacksonville, Florida, 32204, United States

Location

Tampa Medical Group Pa

Tampa, Florida, 33614, United States

Location

Sonora Clinical Research, LLC

Boise, Idaho, 83702, United States

Location

Coeur D'Alene Arthritis Clinic

Coeur d'Alene, Idaho, 83814, United States

Location

The Arthritis Center

Springfield, Illinois, 62704, United States

Location

St. Francis Hospital and Health Centers

Michigan City, Indiana, 46360, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Justus Fiechtner MD PC

Lansing, Michigan, 48910, United States

Location

Physicians East

Greenville, North Carolina, 27834, United States

Location

Carolina Bone and Joint

Monroe, North Carolina, 28112, United States

Location

Piedmont Medical Research Associates Inc

Winston-Salem, North Carolina, 27103-3914, United States

Location

Health Research of Oklahoma

Oklahoma City, Oklahoma, 73103, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Clinical Research Center of Reading, LLP

West Reading, Pennsylvania, 19610, United States

Location

Dermatology Treatment and Research Center

Dallas, Texas, 75230, United States

Location

Accurate Clinical Research Inc

Houston, Texas, 77034, United States

Location

Arthritis and Osteoporosis Associates LLP

Lubbock, Texas, 79424, United States

Location

Center for Clinical Studies

Webster, Texas, 77598, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Seattle Rheumatology Associates

Seattle, Washington, 98104, United States

Location

Arthritis Northwest Rheumatology

Spokane, Washington, 99204, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Eastern Health Clinical School

Box Hill, 3128, Australia

Location

Repatriation General Hospital

Daws Park, 5041, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, 3065, Australia

Location

Emeritus Research

Malvern, 3145, Australia

Location

Ordination Wien Dr. Hanusch

Vienna, 1060, Austria

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

Kaiser-Franz-Josef Spital

Vienna, 1100, Austria

Location

Nexus Clinical Research

St. John's, Newfoundland and Labrador, A1A 5E8, Canada

Location

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

St. John's, Newfoundland and Labrador, A1C-5B8, Canada

Location

Ultranova Skincare

Barrie, Ontario, L4M 6L2, Canada

Location

MAC Research Incorporated

Hamilton, Ontario, L8N 2B6, Canada

Location

K-W Musculoskeletal Research Inc.

Kitchener, Ontario, N2M 5N6, Canada

Location

Saint Josephs Healthcare System

London, Ontario, N6A 4V2, Canada

Location

Credit Valley Professional Building

Mississauga, Ontario, L5M 2V8, Canada

Location

The Arthritis Program Research Group Inc.

Newmarket, Ontario, L3Y 3R7, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 258, Canada

Location

Probity Medical Research Inc

Waterloo, Ontario, N2J 1C4, Canada

Location

Jude Rodrigues Private Practice

Windsor, Ontario, N8X 5A6, Canada

Location

Hospital Maisonneuve - Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Institut de Rhumatologie de Montreal

Montreal, Quebec, H2L 1S6, Canada

Location

Centre de Rhumatologie St-Louis

Sainte-Foy, Quebec, G1W 4R4, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke-Hospital Fleurimont

Sherbrooke, Quebec, J1H5N4, Canada

Location

Saskatoon Osteoporosis Centre

Saskatoon, Saskatchewan, S7K 0H6, Canada

Location

Ipros - Chr Orleans

Orléans, 45067, France

Location

Hopital Purpan

Toulouse, 31009, France

Location

Klinikum Duisburg, Wedau Kliniken

Duisburg, 47055, Germany

Location

Friedrich-Alexander-Universiät Erlangen Nürnberg

Erlangen, 91054, Germany

Location

Allgemeines Krankenhaus Eilbeck

Hamburg, 22081, Germany

Location

Rheumazentrum Ruhrgebiet

Herne, 44652, Germany

Location

Praxis Prof. Herbert Kellner

München, 80639, Germany

Location

Qualiclinic kft

Budapest, 1036, Hungary

Location

Synexus Magyarország Kft.

Budapest, 1036, Hungary

Location

Honvéd Kórház - Állami Egészségügyi Központ

Budapest, 1062, Hungary

Location

MAV Korhaz es Rendelointezet Szolnok

Szolnok, 5000, Hungary

Location

Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet

Veszprém, 8200, Hungary

Location

P3 Research

Crofton Downs, 6035, New Zealand

Location

Waikato hospital

Hamilton, 3204, New Zealand

Location

Middlemore Clinical Trials

New Zealand, 1640, New Zealand

Location

Queen Elizabeth Hospital for Rheumatic Disease

Rotorua, 3201, New Zealand

Location

North Shore Hospital

Takapuna, 1309, New Zealand

Location

Timaru Hospital

Timaru, 8601, New Zealand

Location

Szpital Uniwersytecki im. Dr A.Jurasza

Bydgoszcz, 85-096, Poland

Location

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Synexus SCM Sp. z o.o.

Gdynia, 81-384, Poland

Location

Synexus SCM Sp. z o.o.

Katowice, Poland, Poland

Location

Wojewodzki Zespol Reumatologiczny

Sopot, 81-759, Poland

Location

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

Warsaw, 01-192, Poland

Location

Kemerovo State Medical Academy

Kemerovo, 650066, Russia

Location

Ryazan I.P. Pavlov State Medical University

Ryazan, 390026, Russia

Location

Departmental Hospital at Smolensk Station RZhD JSC

Smolensk, 214025, Russia

Location

Regional Clinical Hospital

Vladimir, 600023, Russia

Location

Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy

Voronezh, 394066, Russia

Location

Panorama Medical Centre

Cape Town, 7500, South Africa

Location

Groote Schuur Hospital

Cape Town, 7925, South Africa

Location

Chelmsford Medical Centre 2

Durban, 4001, South Africa

Location

Clinresco Centres Pty Ltd

Johannesburg, 1619, South Africa

Location

The Park

Pinelands, 7700, South Africa

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Barnsley Hospital

Barnsley South Yorkshire, S75 2EP, United Kingdom

Location

Colchester General Hospital

Colchester, CO4 5JL, United Kingdom

Location

West Suffolk Hospital

Edmunds, IP33 2QZ, United Kingdom

Location

Related Publications (7)

• Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, Hochfeld M, Teng LL, Schett G, Lespessailles E, Hall S. Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis. J Rheumatol. 2015 Mar;42(3):479-88. doi: 10.3899/jrheum.140647. Epub 2015 Jan 15.

  PMID: 25593233 RESULT

• 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.

  PMID: 37316690 DERIVED

• 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.

  PMID: 34536218 DERIVED

• 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.

  PMID: 31909868 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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.

  PMID: 24595547 DERIVED

MeSH Terms

Conditions

Arthritis, Psoriatic; Psoriasis; Arthritis; Inflammation; Skin Diseases

Interventions

apremilast

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Skin Diseases, Papulosquamous; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Anne McClain, Senior 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2010
• First Posted: July 30, 2010
• Study Start: June 2, 2010
• Primary Completion: April 27, 2012
• Study Completion: October 27, 2016
• Last Updated: June 19, 2020
• Results First Posted: May 20, 2014

Record last verified: 2020-06

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

HU (5); NZ (6); US (27); FR (2); AU (5); CA (16); ZA (5); ES (4); DE (5); PL (6); RU (5); GB (3)