PALACE 2: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

NCT01212757 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-10004-PSA-0032010-018386-32
• Study Type: interventional
• Target: 488
• Locations: 15 countries
• Sites: 95

Brief Summary

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

Conditions

Psoriatic Arthritis

Keywords

Psoriasis; Arthritis; Psoriatic 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 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 20mg

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 20mg

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) PsA 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 (98)

Clinical and Translational Research Center of Alabama, PC

Tuscaloosa, Alabama, 35406, United States

Location

Denver Arthritis Clinic

Denver, Colorado, 80230, United States

Location

New England Research Associates, LLC

Trumbull, Connecticut, 6611, United States

Location

Centre For Rheumatology, Immun. And Arthritis

Fort Lauderdale, Florida, 33334, United States

Location

DMI Research

St. Petersburg, Florida, 33710, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Arthritis and Rheumatology of Georgia

Atlanta, Georgia, 30342, United States

Location

Michael Bukhalo MD SC

Arlington Hts, Illinois, 60005, United States

Location

Associated Internal Medical Specialist, PC

Battle Creek, Michigan, 49015, United States

Location

Advanced Rheumatology

Lansing, Michigan, 48910, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Research West Incorporated

Kalispell, Montana, 59901, United States

Location

University of Rochester Medical Center

Rochester, New York, 14623, United States

Location

Vital Research

Greensboro, North Carolina, 27408, United States

Location

Unifour Medical Research Associatets LLC

Hickory, North Carolina, 28602, United States

Location

Rheumatic Disease Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

Location

Baylor Research Institute

Dallas, Texas, 75246-1613, United States

Location

Arthritis Care and Diagnostic Center

Dallas, Texas, 75321, United States

Location

Luckster Enterprises

San Antonio, Texas, 78232, United States

Location

Seattle Rheumatology Associates

Seattle, Washington, 98104, United States

Location

Tacoma Center for Arthritis Research, PS

Tacoma, Washington, 98405, United States

Location

Rheumatology and Immunotherapy Center

Franklin, Wisconsin, 53132, United States

Location

CHU Brugmann

Brussels, 1020, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University Hospital of Liege CHU Liege

Liège, 4000, Belgium

Location

Diagnostic and Consulting Centre 7

Sofia, 1233, Bulgaria

Location

University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia

Sofia, 1407, Bulgaria

Location

17 Diagnostic and Consulting Centre Sofia EOOD

Sofia, 1505, Bulgaria

Location

Multiprofile Hospital for Active Treatment Sv. Ivan Rilski

Sofia, 1612, Bulgaria

Location

Diagnostic-Consultative Center Sveta Anna

Sofia, 1709, Bulgaria

Location

Diagnostic and Consulting Centre 4

Varna, 9010, Bulgaria

Location

Rheumatology Research Associates

Edmonton, Alberta, T5M 0H4, Canada

Location

PerCuro Clinical Research

Victoria, British Columbia, V8P5P6, Canada

Location

Anna Jaroszynska Private Practice

Burlington, Ontario, L7L0B7, Canada

Location

William Bensen's Private Practice

Hamilton, Ontario, L8N1Y2, Canada

Location

North Bay Dermatology Center

North Bay, Ontario, P1B 3Z7, Canada

Location

Rheumatology Research Associates

Ottawa, Ontario, K1H 1A2, Canada

Location

Wilderman Medical Clinic

Thornhill, Ontario, L4J1W3, Canada

Location

Darryl Toth's Private Practice

Windsor, Ontario, N8W 1E6, Canada

Location

Revmatologie s.r.o.

Brno, 638 00, Czechia

Location

MEDIPONT PLUS s.r.o..

České Budějovice, 370 01, Czechia

Location

L.K.N. Arthrocentrum s.r.o.

Hlučín, 748 01, Czechia

Location

ARTMEDI UPD s.r.o.

Hostivice, 253 01, Czechia

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Revmatologicka Ambulance

Prague, 140 00, Czechia

Location

Affidea Praha s.r.o

Prague, 148 00, Czechia

Location

Revmatologicka Ambulance

Sokolov, 356 01, Czechia

Location

PV - MEDICAL, s.r.o.

Zlín, 760 01, Czechia

Location

Parnu Hospital

Pärnu, EE-80010, Estonia

Location

East Tallinn Central Hospital

Tallinn, EE-11412, Estonia

Location

North Estonia Regional Hospital

Tallinn, EE-13419, Estonia

Location

Clinical Research Centre Ltd

Tartu, 50106, Estonia

Location

Tartu University Hospital

Tartu, EE-51014, Estonia

Location

Hopital Universitaire Dupuytren

Limoges, 87042, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Fondation Hôpital Saint-Joseph

Paris, 75014, France

Location

Groupe Hospitalier Pitié- Salpétrière

Paris, 75651, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Charite - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Klinikum der Johann-Wolfgang Goethe-Universität

Frankfurt, 60590, Germany

Location

Praxis Karin Rockwitz

Goslar, 38642, Germany

Location

Synexus Clinical Research GmbH

Leipzig, 4103, Germany

Location

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Principal SMO Kft.

Makó, 6900, Hungary

Location

Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Ospedale Luigi Sacco

Milan, 20157, Italy

Location

Seconda Universita degli Studi di Napoli

Napoli, 80130, Italy

Location

IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Universita di Pisa

Pisa, 56126, Italy

Location

Ospedale Civile Maggiore Borgo Trento

Verona, 37126, Italy

Location

NZOZ Osteo-Medic sc A. Racewicz J. Supronik

Bialystok, 15-351, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej REUMED

Lublin, 20-582, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 00-909, Poland

Location

Instytut Reumatologii im. prof. dr hab. med. Eleonory Reicher

Warsaw, 02-637, Poland

Location

Synexus SCM Sp. z o.o.

Wroclaw, 50-088, Poland

Location

City Clinical Hospital #1 n.a. N.I.Pirogov

Moscow, 119049, Russia

Location

City Clinical Hospital #5

Nizhny Novgorod, 603005, Russia

Location

St.Petersburg State Medical Academy n. a. I.I.Mechnikov

Saint Petersburg, 195067, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, 150062, Russia

Location

Nelson Mandela School Of Medicine

Durban, 4091, South Africa

Location

Greenacres Hospital

Port Elizabeth, 6057, South Africa

Location

Jacaranda Hospital

Pretoria, 2, South Africa

Location

Hospital General Carlos Haya

Málaga, 29009, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Sierrallana

Torrelavega, 39300, Spain

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Cathay General Hospital

Taipei, 106, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

National Taiwan University Hospital

Tapei, 10002, Taiwan

Location

Basingstoke and North Hampshire Hospital

Basingstoke, RG24 9NA, United Kingdom

Location

Cannock Chase Hospital

Cannock, WS11 5XY, United Kingdom

Location

Chapel Allerton Hospital

Leeds, LS7 4SA, United Kingdom

Location

Poole Hospital

Poole, BH 1 5JB, United Kingdom

Location

Great Western Hospital

Swindon, SN3 6BB, United Kingdom

Location

Related Publications (6)

• Cutolo M, Myerson GE, Fleischmann RM, Liote F, Diaz-Gonzalez F, Van den Bosch F, Marzo-Ortega H, Feist E, Shah K, Hu C, Stevens RM, Poder A. A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial. J Rheumatol. 2016 Sep;43(9):1724-34. doi: 10.3899/jrheum.151376. Epub 2016 Jul 15.

  PMID: 27422893 BACKGROUND

• 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

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: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

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: September 29, 2010
• First Posted: October 1, 2010
• Study Start: September 27, 2010
• Primary Completion: July 26, 2012
• Study Completion: January 25, 2017
• Last Updated: May 6, 2020
• Results First Posted: May 19, 2014

Record last verified: 2020-04

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 (3); PL (5); TW (5); IT (6); US (23); RU (4); ES (5); BE (4); GB (5); BU (6); CA (8); FR (5); CZ (9); ZA (3); DE (4)