Clinical trial NCT01212770: PALACE 3: Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis and a Qualifying Psoriasis Lesion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: Psoriatic Arthritis
Psoriasis
Arthritis
inflammation
skin condition
inflammatory cells
apremilast
CC-10004
phosphodiesterase type 4
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-10-01
Enrollment: 505
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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) 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

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

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With an ACR 20 Response at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Patient's Assessment of Pain at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Dactylitis Severity Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Disease Activity Score (DAS28) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Patient's Assessment of Pain at Week 24
timeFrame: Baseline and week 24
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24
timeFrame: Baseline and week 24
measure: Change From Baseline in Dactylitis Severity Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Disease Activity Score (DAS28) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With MASES Improvement ≥ 20% at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With MASES Improvement ≥ 20% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Good or Moderate EULAR Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With a ACR 50 Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With an ACR 70 Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With an ACR 50 Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With a ACR 70 Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Achieving a MASES Score of Zero at Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving a MASES Score of Zero at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24
timeFrame: Week 24
measure: Percentage of Participants With an ACR 20 Response at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the SF-36 Physical Functioning Scale Score at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With a Modified PsARC Response at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants Achieving a ≥ 75% Improvement in Psoriasis Area and Severity Index Score (PASI75) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Patient Assessment of Pain at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the Dactylitis Severity Score at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the CDAI Score at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the DAS28 at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With MASES Improvement ≥ 20% at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With an ACR 50 Response at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With an ACR 70 Response at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants Achieving a MASES Score of Zero at Week 52
timeFrame: Week 52
measure: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52
timeFrame: Week 52
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
timeFrame: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
measure: Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period
timeFrame: Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 121.71 weeks and 232.50 weeks for apremilast 30 mg BID
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Tucson
country: United States
facility: Catalina Pointe Clinical Research Incorporated
state: Arizona
city: Bakersfield
country: United States
facility: Bakersfield Dermatology and Skin Cancer Medical Group
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Bridgeport
country: United States
facility: Joao Nascimento, MD
state: Connecticut
city: Doral
country: United States
facility: In Vivo Clinical Research
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Orlando
country: United States
facility: Rheumatology Associates of Long Island
state: Florida
city: Pinellas Park
country: United States
facility: Advent Clinical Research
state: Florida
city: Rockford
country: United States
facility: Rockford Orthopedic Associates, LLC
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Louisville
country: United States
facility: DermResearch, PLLC
state: Kentucky
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dayton
country: United States
facility: STAT Research, Inc.
state: Ohio
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Austin
country: United States
facility: Austin Dermatology Associates
state: Texas
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: Houston
country: United States
facility: Houston Medical Research
state: Texas
city: Sugar Land
country: United States
facility: Texas Research Center
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Carlton
country: Australia
facility: Skin Cancer Foundation
city: Coffs Harbour
country: Australia
facility: Coff's Clinical Trials
city: Heidelberg
country: Australia
facility: Heidelberg Repatriation Hospital
city: Hobart
country: Australia
facility: Menzies Centre for Population Health Research
city: Kogarah
country: Australia
facility: Optimus Clinical Research Pty. Ltd
city: Maroochydore
country: Australia
facility: Coastal Joint Care
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Vancouver
country: Canada
facility: Arthritis Research Centre of Canada
state: British Columbia
city: Victoria
country: Canada
facility: PerCuro Clinical Research
state: British Columbia
city: Winnipeg
country: Canada
facility: Manitoba Clinic
state: Manitoba
city: Winnipeg
country: Canada
facility: Arthritis Centre
state: Manitoba
city: St John's
country: Canada
facility: Alpha Clinical Research, LLC
state: Newfoundland and Labrador
city: St Catharines
country: Canada
facility: Niagara Peninsula Arthritis Centre Inc.
state: Ontario
city: Toronto
country: Canada
facility: Manna Research
state: Ontario
city: Helsinki
country: Finland
facility: Helsingin Reumakeskus Oy
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Pori
country: Finland
facility: Finnish Medical Research Co
city: Corbeil Essonnes
country: France
facility: Centre Hospitalier Sud Francilien - Site Gilles de Corbeil
city: Nantes
country: France
facility: Hôtel-Dieu
city: Nice
country: France
facility: Groupe Hospitalier Archet I et II
city: Toulouse
country: France
facility: Hopital Larrey Universite Paul Sabatier
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Klinische Forschung Berlin - Buch GmbH
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller-Universität Jena
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
city: Anyang, Kyunggi
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: DaeJeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hosiptal
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University Health and Sciences
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital
city: Panevezys
country: Lithuania
facility: Panevezys Hospital
city: Siauliai
country: Lithuania
facility: Siauliai Hospital
city: Bialystok
country: Poland
facility: Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
city: Bytom
country: Poland
facility: Centrum Medyczne Silesiana Sp. z o.o.
city: Kraków
country: Poland
facility: Malopolskie Centrum Medyczne S.C.
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Pawel Hrycaj
city: Warszawa
country: Poland
facility: REUMATIKA-Centrum Reumatologii Niepubliczny Zaklad Opieki Zdrowotnej
city: Baia Mare
country: Romania
facility: Baia Mare, Emergency County Hospital "Dr. Constantin Opris"
city: Bucharest
country: Romania
facility: SC Duo Medical SRL
city: Bucharest
country: Romania
facility: Sf. Maria Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Emergency County Clinical Hospital
city: Galati
country: Romania
facility: Sf Apostol Andrei Emergency Clinical County Hospital
city: Iasi
country: Romania
facility: C.M.I. Dr. Ciornohuz Adriana
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital 1
city: Kezch
country: Russian Federation
facility: Research Medical Complex Vashe Zdorovie
city: Novosibirsk
country: Russian Federation
facility: Research Institute of Clinical and Experimental Lymphology
city: Penza
country: Russian Federation
facility: Penza Regional Clinical Hospital n.a. N.N. Burdenko
city: St. Petersburg
country: Russian Federation
facility: City Hospital 26
city: Piestany
country: Slovakia
facility: Narodny ustav reumatickych chorob
city: Poprad,Spisska Sobota
country: Slovakia
facility: MUDr. Zuzana Cizmarikova, s.r.o.
city: Rimavska Sobota
country: Slovakia
facility: REUMEX s.r.o.
city: A Coruña
country: Spain
facility: Hospital Universitario a Coruna
city: Bilbao
country: Spain
facility: Hospital de Basurto-Osakidetza
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: San Sebastian de los Reyes
country: Spain
facility: Hospital Infanta Sofia
city: Fribourg
country: Switzerland
facility: HFR Fribourg - Hôpital Cantonal
city: Lausanne
country: Switzerland
facility: Chuv Bh-04
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Burslem
country: United Kingdom
facility: Haywood Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.