Clinical trial NCT01212757: PALACE 2: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: Psoriasis
Arthritis
Psoriatic Arthritis
inflammation
skin condition
inflammatory cells
apremilast
CC-10004
phosphodiesterase type 4
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-10-01
Enrollment: 488
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.

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) 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.

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: 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: 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 a 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: 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 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 TEAEs During the Apremilast-Exposure Period
timeFrame: Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Clinical and Translational Research Center of Alabama, PC
state: Alabama
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Trumbull
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Centre For Rheumatology, Immun. And Arthritis
state: Florida
city: Saint Petersburg
country: United States
facility: DMI Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Arthritis and Rheumatology of Georgia
state: Georgia
city: Arlington Hts
country: United States
facility: Michael Bukhalo MD SC
state: Illinois
city: Battle Creek
country: United States
facility: Associated Internal Medical Specialist, PC
state: Michigan
city: Lansing
country: United States
facility: Advanced Rheumatology
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kalispell
country: United States
facility: Research West Incorporated
state: Montana
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Greensboro
country: United States
facility: Vital Research
state: North Carolina
city: Hickory
country: United States
facility: Unifour Medical Research Associatets LLC
state: North Carolina
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: Arthritis Care and Diagnostic Center
state: Texas
city: San Antonio
country: United States
facility: Luckster Enterprises
state: Texas
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
city: Tacoma
country: United States
facility: Tacoma Center for Arthritis Research, PS
state: Washington
city: Franklin
country: United States
facility: Rheumatology and Immunotherapy Center
state: Wisconsin
city: Bruxelles
country: Belgium
facility: CHU Brugmann
city: Ghent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: University Hospital of Liege CHU Liege
city: Sofia
country: Bulgaria
facility: Diagnostic and Consulting Centre 7
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
city: Sofia
country: Bulgaria
facility: 17 Diagnostic and Consulting Centre Sofia EOOD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Sv. Ivan Rilski
city: Sofia
country: Bulgaria
facility: Diagnostic-Consultative Center Sveta Anna
city: Varna
country: Bulgaria
facility: Diagnostic and Consulting Centre 4
city: Edmonton
country: Canada
facility: Rheumatology Research Associates
state: Alberta
city: Victoria
country: Canada
facility: PerCuro Clinical Research
state: British Columbia
city: Burlington
country: Canada
facility: Anna Jaroszynska Private Practice
state: Ontario
city: Hamilton
country: Canada
facility: William Bensen's Private Practice
state: Ontario
city: North Bay
country: Canada
facility: North Bay Dermatology Center
state: Ontario
city: Ottawa
country: Canada
facility: Rheumatology Research Associates
state: Ontario
city: Thornhill
country: Canada
facility: Wilderman Medical Clinic
state: Ontario
city: Windsor
country: Canada
facility: Darryl Toth's Private Practice
state: Ontario
city: Brno
country: Czechia
facility: Revmatologie s.r.o.
city: Ceske Budejovice
country: Czechia
facility: MEDIPONT PLUS s.r.o..
city: Hlucin
country: Czechia
facility: L.K.N. Arthrocentrum s.r.o.
city: Hostivice
country: Czechia
facility: ARTMEDI UPD s.r.o.
city: Praha 11
country: Czechia
facility: Affidea Praha s.r.o
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Praha 4
country: Czechia
facility: Revmatologicka Ambulance
city: Sokolov
country: Czechia
facility: Revmatologicka Ambulance
city: Zlin
country: Czechia
facility: PV - MEDICAL, s.r.o.
city: Pärnu
country: Estonia
facility: Parnu Hospital
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: North Estonia Regional Hospital
city: Tartu
country: Estonia
facility: Clinical Research Centre Ltd
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Limoges
country: France
facility: Hopital Universitaire Dupuytren
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Fondation Hôpital Saint-Joseph
city: Paris
country: France
facility: Groupe Hospitalier Pitié- Salpétrière
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universität
city: Goslar
country: Germany
facility: Praxis Karin Rockwitz
city: Leipzig
country: Germany
facility: Synexus Clinical Research GmbH
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Makó
country: Hungary
facility: Principal SMO Kft.
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Napoli
country: Italy
facility: Seconda Universita degli Studi di Napoli
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Universita di Pisa
city: Verona
country: Italy
facility: Ospedale Civile Maggiore Borgo Trento
city: Bialystok
country: Poland
facility: NZOZ Osteo-Medic sc A. Racewicz J. Supronik
city: Lublin
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej REUMED
city: Warsaw
country: Poland
facility: Instytut Reumatologii im. prof. dr hab. med. Eleonory Reicher
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Wroclaw
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #1 n.a. N.I.Pirogov
city: Nizhniy Novgorod
country: Russian Federation
facility: City Clinical Hospital #5
city: St. Petersburg
country: Russian Federation
facility: St.Petersburg State Medical Academy n. a. I.I.Mechnikov
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
city: Durban
country: South Africa
facility: Nelson Mandela School Of Medicine
city: Port Elizabeth
country: South Africa
facility: Greenacres Hospital
city: Pretoria
country: South Africa
facility: Jacaranda Hospital
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Málaga
country: Spain
facility: Hospital General Carlos Haya
city: Torrelavega
country: Spain
facility: Hospital Sierrallana
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Cathay General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Tapei
country: Taiwan
facility: National Taiwan University Hospital
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
city: Cannock
country: United Kingdom
facility: Cannock Chase Hospital
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Swindon
country: United Kingdom
facility: Great Western Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
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.