Clinical trial NCT01172938: 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: Psoriatic Arthritis
Psoriasis
Arthritis
inflammation
skin condition
inflammatory cells
apremilast
CC-10004
phosphodiesterase type 4
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-07-30
Enrollment: 504
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, specifically in improving 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) 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 SF-36 Physical Function 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 Domain 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 Adverse Events During the Placebo-Controlled Period
timeFrame: Week 0 to Week 16 for placebo participants who entered early escape 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 Adverse Events During the Apremilast-Exposure Period
timeFrame: Baseline to Week 260; median total exposure to Apremilast was 170 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research LLC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: La Jolla
country: United States
facility: UCSD-Thornton Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials
state: California
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Jacksonville
country: United States
facility: North Florida Dermatology
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group Pa
state: Florida
city: Boise
country: United States
facility: Sonora Clinical Research, LLC
state: Idaho
city: Coeur d'Alene
country: United States
facility: Coeur D'Alene Arthritis Clinic
state: Idaho
city: Springfield
country: United States
facility: The Arthritis Center
state: Illinois
city: Michigan City
country: United States
facility: St. Francis Hospital and Health Centers
state: Indiana
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Lansing
country: United States
facility: Justus Fiechtner MD PC
state: Michigan
city: Greenville
country: United States
facility: Physicians East
state: North Carolina
city: Monroe
country: United States
facility: Carolina Bone and Joint
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates Inc
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: West Reading
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Dallas
country: United States
facility: Dermatology Treatment and Research Center
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research Inc
state: Texas
city: Lubbock
country: United States
facility: Arthritis and Osteoporosis Associates LLP
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology
state: Washington
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Box Hill
country: Australia
facility: Eastern Health Clinical School
city: Daws Park
country: Australia
facility: Repatriation General Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Malvern
country: Australia
facility: Emeritus Research
city: Vienna
country: Austria
facility: Ordination Wien Dr. Hanusch
city: Vienna
country: Austria
facility: Medizinische Universitat Wien
city: Wien
country: Austria
facility: Kaiser-Franz-Josef Spital
city: St John's
country: Canada
facility: Nexus Clinical Research
state: Newfoundland and Labrador
city: St John's
country: Canada
facility: St. Clare's Health Care Corporation of St. John's
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: Ultranova Skincare
state: Ontario
city: Hamilton
country: Canada
facility: MAC Research Incorporated
state: Ontario
city: Kitchener
country: Canada
facility: K-W Musculoskeletal Research Inc.
state: Ontario
city: London
country: Canada
facility: Saint Josephs Healthcare System
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Professional Building
state: Ontario
city: Newmarket
country: Canada
facility: The Arthritis Program Research Group Inc.
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Waterloo
country: Canada
facility: Probity Medical Research Inc
state: Ontario
city: Windsor
country: Canada
facility: Jude Rodrigues Private Practice
state: Ontario
city: Montreal
country: Canada
facility: Hospital Maisonneuve - Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Institut de Rhumatologie de Montreal
state: Quebec
city: Sainte Foy
country: Canada
facility: Centre de Rhumatologie St-Louis
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke-Hospital Fleurimont
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Osteoporosis Centre
state: Saskatchewan
city: Orleans
country: France
facility: Ipros - Chr Orleans
city: Toulouse Cedex
country: France
facility: Hopital Purpan
city: Duisburg
country: Germany
facility: Klinikum Duisburg, Wedau Kliniken
city: Erlangen
country: Germany
facility: Friedrich-Alexander-Universiät Erlangen Nürnberg
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus Eilbeck
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: München
country: Germany
facility: Praxis Prof. Herbert Kellner
city: Budapest
country: Hungary
facility: Qualiclinic kft
city: Budapest
country: Hungary
facility: Synexus Magyarország Kft.
city: Budapest
country: Hungary
facility: Honvéd Kórház - Állami Egészségügyi Központ
city: Szolnok
country: Hungary
facility: MAV Korhaz es Rendelointezet Szolnok
city: Veszprém
country: Hungary
facility: Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet
city: Crofton Downs
country: New Zealand
facility: P3 Research
city: Hamilton
country: New Zealand
facility: Waikato hospital
city: New Zealand
country: New Zealand
facility: Middlemore Clinical Trials
city: Rotorua
country: New Zealand
facility: Queen Elizabeth Hospital for Rheumatic Disease
city: Takapuna
country: New Zealand
facility: North Shore Hospital
city: Timaru
country: New Zealand
facility: Timaru Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. Dr A.Jurasza
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Gdynia
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Katowice
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Sopot
country: Poland
facility: Wojewodzki Zespol Reumatologiczny
city: Warszawa
country: Poland
facility: Synexus SCM Sp. z o.o. Oddz. Warszawa
city: Kemerovo
country: Russian Federation
facility: Kemerovo State Medical Academy
city: Ryazan
country: Russian Federation
facility: Ryazan I.P. Pavlov State Medical University
city: Smolensk
country: Russian Federation
facility: Departmental Hospital at Smolensk Station RZhD JSC
city: Vladimir
country: Russian Federation
facility: Regional Clinical Hospital
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy
city: Cape Town
country: South Africa
facility: Panorama Medical Centre
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Durban
country: South Africa
facility: Chelmsford Medical Centre 2
city: Johannesburg
country: South Africa
facility: Clinresco Centres Pty Ltd
city: Pinelands
country: South Africa
facility: The Park
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Barnsley South Yorkshire
country: United Kingdom
facility: Barnsley Hospital
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: Edmunds
country: United Kingdom
facility: West Suffolk Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
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.
citation: 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.