PALACE 3: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis

NCT01212770 | Completed Phase 3 Results DMC

• 1 other identifier: CC-10004-PSA-004
• Study Type: interventional
• Target: 505
• Locations: 16 countries
• Sites: 91

Brief Summary

The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis and a qualifying psoriasis lesion. 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

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 (55)

• 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 30 mg

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

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

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 30 mg

Placebo DRUG

Placebo + 20 mg Apremilast; 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) criteria for PsA at time of screening.
• Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)
• May not have axial involvement alone
• Concurrent Tx allowed with methotrexate, leflunomide, or sulfasalazine
• Have ≥ 3 swollen AND ≥ 3 tender joints.
• Males \& Females must use contraception
• Stable dose of NSAIDs, narcotics and low dose oral corticosteroids allowed.
• Have at least one ≥2 cm psoriasis lesion

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 (91)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Elite Clinical Studies, LLC

Phoenix, Arizona, 85018, United States

Location

Catalina Pointe Clinical Research Incorporated

Tucson, Arizona, 85704, United States

Location

Bakersfield Dermatology and Skin Cancer Medical Group

Bakersfield, California, 93309, United States

Location

Dermatology Research Associates

Los Angeles, California, 90045, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Joao Nascimento, MD

Bridgeport, Connecticut, 6606, United States

Location

In Vivo Clinical Research

Doral, Florida, 33166, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

Rheumatology Associates of Long Island

Orlando, Florida, 32806, United States

Location

Advent Clinical Research

Pinellas Park, Florida, 33781, United States

Location

Rockford Orthopedic Associates, LLC

Rockford, Illinois, 61107, United States

Location

Dawes Fretzin Clinical Research Group, LLC

Indianapolis, Indiana, 46256, United States

Location

DermResearch, PLLC

Louisville, Kentucky, 40217, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01605, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

STAT Research, Inc.

Dayton, Ohio, 45417, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Austin Dermatology Associates

Austin, Texas, 78705, United States

Location

Austin Regional Clinic

Austin, Texas, 78731, United States

Location

Center for Clinical Studies

Houston, Texas, 77065, United States

Location

Houston Medical Research

Houston, Texas, 77090, United States

Location

Texas Research Center

Sugar Land, Texas, 77479, United States

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Skin Cancer Foundation

Carlton, 3053, Australia

Location

Coff's Clinical Trials

Coffs Harbour, 2450, Australia

Location

Heidelberg Repatriation Hospital

Heidelberg, 3081, Australia

Location

Menzies Centre for Population Health Research

Hobart, 7000, Australia

Location

Optimus Clinical Research Pty. Ltd

Kogarah, 2217, Australia

Location

Coastal Joint Care

Maroochydore, 4558, Australia

Location

The Queen Elizabeth Hospital

Woodville, 5011, Australia

Location

Arthritis Research Centre of Canada

Vancouver, British Columbia, V5Z1L7, Canada

Location

PerCuro Clinical Research

Victoria, British Columbia, V8P5P6, Canada

Location

Manitoba Clinic

Winnipeg, Manitoba, R3A1M3, Canada

Location

Arthritis Centre

Winnipeg, Manitoba, R3A1M4, Canada

Location

Alpha Clinical Research, LLC

St. John's, Newfoundland and Labrador, A1B 4S8, Canada

Location

Niagara Peninsula Arthritis Centre Inc.

St. Catharines, Ontario, L2N 7E4, Canada

Location

Manna Research

Toronto, Ontario, M9W4L6, Canada

Location

Helsingin Reumakeskus Oy

Helsinki, FI-00120, Finland

Location

Helsingin yliopistollinen keskussairaala

Helsinki, FI-00290, Finland

Location

Finnish Medical Research Co

Pori, FI-28100, Finland

Location

Centre Hospitalier Sud Francilien - Site Gilles de Corbeil

Corbeil-Essonnes, 91106, France

Location

Hôtel-Dieu

Nantes, 44093, France

Location

Groupe Hospitalier Archet I et II

Nice, 6002, France

Location

Hopital Larrey Universite Paul Sabatier

Toulouse, 31000, France

Location

Charite - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Klinische Forschung Berlin - Buch GmbH

Berlin, 13125, Germany

Location

Klinikum der Friedrich-Schiller-Universität Jena

Jena, 7740, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 133, Italy

Location

Hospital of Lithuanian University Health and Sciences

Kaunas, LT-50009, Lithuania

Location

Klaipeda University Hospital

Klaipėda, LT-5808, Lithuania

Location

Panevezys Hospital

Panevezys, LT-35144, Lithuania

Location

Siauliai Hospital

Šiauliai, LT-76231, Lithuania

Location

Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk

Bialystok, 15-099, Poland

Location

Centrum Medyczne Silesiana Sp. z o.o.

Bytom, 41-902, Poland

Location

Malopolskie Centrum Medyczne S.C.

Krakow, 30-510, Poland

Location

Prywatna Praktyka Lekarska Pawel Hrycaj

Poznan, 61-397, Poland

Location

REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej

Warsaw, 02-653, Poland

Location

Baia Mare, Emergency County Hospital "Dr. Constantin Opris"

Baia Mare, 430031, Romania

Location

SC Duo Medical SRL

Bucharest, 10584, Romania

Location

Sf. Maria Clinical Hospital

Bucharest, 11172, Romania

Location

Emergency County Clinical Hospital

Cluj-Napoca, 400006, Romania

Location

Sf Apostol Andrei Emergency Clinical County Hospital

Galati, 800578, Romania

Location

C.M.I. Dr. Ciornohuz Adriana

Iași, 700127, Romania

Location

Research Medical Complex Vashe Zdorovie

Kezch, 214025, Russia

Location

Research Institute of Clinical and Experimental Lymphology

Novosibirsk, 630117, Russia

Location

Penza Regional Clinical Hospital n.a. N.N. Burdenko

Penza, 440026, Russia

Location

City Hospital 26

Saint Petersburg, 196247, 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.

Poprad,Spisska Sobota, 058 01, Slovakia

Location

REUMEX s.r.o.

Rimavská Sobota, 979 01, Slovakia

Location

Hallym University Sacred Heart Hospital

Anyang, Kyunggi, 431070, South Korea

Location

Chungnam National University Hospital

Daejeon, 301-721, South Korea

Location

Inha University Hosiptal

Incheon, 400-711, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405760, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 120-752, South Korea

Location

Ajou University Hospital

Suwon, 443-721, South Korea

Location

Hospital Universitario a Coruna

A Coruña, 15006, Spain

Location

Hospital de Basurto-Osakidetza

Bilbao, 48013, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Hospital Infanta Sofia

San Sebastián de los Reyes, 28702, Spain

Location

HFR Fribourg - Hôpital Cantonal

Fribourg, 1708, Switzerland

Location

Chuv Bh-04

Lausanne, 1011, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Haywood Hospital

Burslem, ST6 7AG, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (6)

• Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion J, Stevens RM, Vessey A, Zhan X, Bird P. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016 Jun;75(6):1065-73. doi: 10.1136/annrheumdis-2015-207963. Epub 2016 Jan 20.

  PMID: 26792812 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

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
• 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 30, 2010
• Primary Completion: August 21, 2012
• Study Completion: February 9, 2017
• Last Updated: May 6, 2020
• Results First Posted: May 20, 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

IT (2); US (23); PL (5); RO (6); SL (3); CH (3); GB (2); ES (5); CA (7); DE (4); FI (3); KR (7); FR (4); RU (5); LI (4); AU (8)