Clinical trial NCT01690299: Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis
Official title: A Phase 3B, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Double-Dummy, Study Of The Efficacy And Safety Of Apremilast (CC-10004), Etanercept, And Placebo, In Subjects With Moderate To Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Psoriatic Arthritis
Keywords: Psoriasis
arthritis
psoriatic
palmoplantar
scalp
psoriasis pill
psoriasis tablet
plaque psoriasis
plaque type psoriasis
moderate to severe plaque type psoriasis
psoriatic arthritis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 250
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: This study will test the clinical effectiveness and safety of apremilast compared with placebo as well as etanercept compared with placebo in the same group of patients with moderate to severe plaque psoriasis.

Detailed description: This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind, double-dummy, study of the efficacy and safety of apremilast, etanercept, and placebo, in adults with moderate to severe plaque psoriasis.

250 participants will be randomized 1:1:1 to the three treatment groups. All subjects will receive both tablets and injections through Week 16.

The study will consist of four phases:

* Screening Phase - up to 35 days
* Double-blind Placebo-controlled Phase - Weeks 0-16
* Apremilast Extension Phase - Weeks 16-104
* Post-treatment Observational Follow-up Phase

During the double-blind, placebo-controlled phase, subjects will receive treatment with one of the following:

* apremilast (APR) 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections (1 mL x 2 injections SC), or
* etanercept (ETN) 50 mg evaluator/subject-blinded subcutaneous (SC) once weekly (QW) injections (2 x 25 mg) plus placebo tablets orally twice a day (BID), or
* placebo tablets and evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections.

All subjects will be asked to participate in a 4-week Post-treatment Observational Follow-up Phase either upon completion of the study or upon discontinuation of investigational product for those subjects who terminate the study early.

Eligibility criteria: Inclusion Criteria:

* Males or females, ≥ 18 years of age
* Diagnosis of chronic, moderate to severe plaque psoriasis for at least 12 months prior to Screening, and a candidate for phototherapy and/or systemic (including etanercept) therapy
* Had an inadequate response, intolerance, or contraindication to at least 1 conventional systemic agent for the treatment of psoriasis.
* No prior exposure to biologics for treatment of psoriatic arthritis or psoriasis

Exclusion Criteria:

* Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
* Pregnant or breast feeding.
* Have failed more than 3 systemic agents for treatment of psoriasis.
* History of allergy to any component of the investigational product (IP), including human immunoglobulin (Ig) proteins or allergy to etanercept.
* Hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.
* Latent, active tuberculosis (TB) or inadequately treated TB; nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, Clostridium difficile).
* Have a history of, or ongoing, chronic or recurrent infectious disease
* Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months before first administration of IP, or through Week 20 during the study.
* Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.
* History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
* Active substance abuse or a history of substance abuse within 6 months prior to Screening.
* Malignancy or history of malignancy, except for treated \[ie, cured\] basal cell or squamous cell in situ skin carcinomas and cervical intraepithelial neoplasia \[CIN\] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years.
* Psoriasis flare or rebound within 4 weeks prior to Screening.
* Topical therapy within 2 weeks of randomization or systemic therapy for psoriasis within 4 weeks prior to randomization
* Use of phototherapy within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
* Any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer).
* Prior treatment with apremilast or etanercept.

Primary outcomes:
measure: Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) for the Comparison Between Apremilast and Placebo at Week 16 From Baseline
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI) for the Comparison Between Etanercept 50mg SC QW and Placebo at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in the Affected Body Surface Area (BSA) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants Who Achieved a 50% Improvement (Response) in the Psoriasis Area Severity Index (PASI-50) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score In Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in the Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants Who Achieved a Lattice System Physician's Global Assessment (LS-PGA) Score of Clear (0) or Almost Clear at Week 16 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16
timeFrame: Baseline to Week 16
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Phase
timeFrame: Week 0 to Week 16; mean duration of exposure was 14.90 weeks for placebo group, 15.13 weeks for apremilast group and 15.87 weeks for Etanercept group
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-exposure Period
timeFrame: From the first dose of apremilast (either Week 0 for participants originally randomized to apremilast or Week 16 for those originally randomized to placebo or etanercept who were switched to apremilast at week 16) until 28 days after last apremilast dose
measure: Psoriasis Flare/Rebound
timeFrame: Week 0 to Week 16; Placebo controlled phase
measure: Psoriasis Flare/Rebound
timeFrame: From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo or etanercept who were switched at Week 16) until 28 days after the last dose of apremilast.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Bakersfield
country: United States
facility: Bakersfield Dermatology and Skin Cancer Medical Group
state: California
city: Irvine
country: United States
facility: University of California Irvine-Department of Dermatology
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Denver
country: United States
facility: Horizons Clinical Research
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Jacksonville
country: United States
facility: Florida Center for Dermatology, PA
state: Florida
city: Miami
country: United States
facility: Florida Academic Dermatology Center
state: Florida
city: Miami
country: United States
facility: International Dermatology Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Alpharetta
country: United States
facility: Atlanta Dermatology, Vein and Research Center, PC
state: Georgia
city: Skokie
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Lake Charles
country: United States
facility: Dermatology and Advanced Aesthetics
state: Louisiana
city: Rockville
country: United States
facility: Lawrence Green, MD, LLC
state: Maryland
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Somerset
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Forest Hills
country: United States
facility: Forest Hills Dermatology Group
state: New York
city: New York
country: United States
facility: NYU Department of Dermatology
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennesse Clinical Research Center
state: Tennessee
city: Austin
country: United States
facility: Teckton Research
state: Texas
city: Lynchburg
country: United States
facility: The Education and Research Foundation
state: Virginia
city: Norfolk
country: United States
facility: Virginia Clinical Research Inc
state: Virginia
city: Seattle
country: United States
facility: Dermatology Associates of Seattle
state: Washington
city: Benowa
country: Australia
facility: The Skin Centre
state: Queensland
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Victoria Park
country: Australia
facility: Gairdner Hospital
city: Woodville
country: Australia
facility: Rheumatology unit Ward 5C Queen Elizabeth Hospital
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Liege
country: Belgium
facility: University Hospital of Liege CHU Liege
city: Halifax
country: Canada
facility: Eastern Canada Cutaneous Research Associates Ltd
state: Nova Scotia
city: Peterborough
country: Canada
facility: Skin Center for Dermatology
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research Inc.
state: Ontario
city: Montreal
country: Canada
facility: Siena Medical Research
state: Quebec
city: Sherbrooke
country: Canada
facility: Q & T Research Sherbrooke Inc.
state: Quebec
city: Chomutov
country: Czechia
facility: Dorothea, Kožní a korektivne dermatologické pracovište
city: Nachod
country: Czechia
facility: Dermamedica
city: Pardubice
country: Czechia
facility: Východoceské dermatologické centrum Homea s.r.o.
city: Pardubice
country: Czechia
facility: Krajská nemocnice Pardubice, Kožní oddelení
city: Svitavy
country: Czechia
facility: Dermatovenerologicka ambulance
city: Ústí nad Labem
country: Czechia
facility: Koznia zilni ambulance
city: Meegomäe Village, Võru County
country: Estonia
facility: South Estonian Hospital Ltd
city: Tartu
country: Estonia
facility: Dermatology Clinic of Tartu University Hospital
city: Berlin
country: Germany
facility: Psoriasis Study Center
city: Berlin
country: Germany
facility: Dermatologische Praxis
city: Berlin
country: Germany
facility: Klinische Forschung Berlin - Buch GmbH
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Erlangen
country: Germany
facility: Hautklinik Universitatsklinikum Erlangen
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Hamburg
country: Germany
facility: SCIderm GmbH
city: Hamburg
country: Germany
facility: Institute for Health Services Research in Dermatology and Nursing - IVDP, University Medical Center
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Leipzig
country: Germany
facility: UniversitatsKlinikum Leipzig A.o.R.
city: Lübeck
country: Germany
facility: Comprehensive Center of Inflammatory Medicine (CCIM) University Medical Center Schleswig-Holstein
city: Mahlow
country: Germany
facility: Gemeinschaftspraxis Mahlow
city: Münster
country: Germany
facility: University Hospital Munster
city: Wuppertal
country: Germany
facility: Praxis fr Dermatologie und Venerologie
city: Szekszárd
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Szolnok
country: Hungary
facility: Allergo-Derm Bakos Kft.
city: Adazi
country: Latvia
facility: LTD M & M centrs
city: Baldone
country: Latvia
facility: Arija's Ancane's Family Doctor Private Practice
city: Riga
country: Latvia
facility: Riga 1st Hospital Skin and Sexually Transmitted Diseases Clinical Centre
city: Riga
country: Latvia
facility: Adoria Ltd
city: Riga
country: Latvia
facility: Family Doctor's Indra's Kenina's Practice
city: Talsi
country: Latvia
facility: Health Center of Talsi Ltd
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals Trust
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
city: London
country: United Kingdom
facility: St Helier Hospital
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Reich K, Mrowietz U, Menter A, Griffiths CEM, Bagel J, Strober B, Nunez Gomez N, Shi R, Guerette B, Lebwohl M. Effect of baseline disease severity on achievement of treatment target with apremilast: results from a pooled analysis. J Eur Acad Dermatol Venereol. 2021 Dec;35(12):2409-2414. doi: 10.1111/jdv.17520. Epub 2021 Aug 23.
citation: Reich K, Gooderham M, Green L, Bewley A, Zhang Z, Khanskaya I, Day RM, Goncalves J, Shah K, Piguet V, Soung J. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE). J Eur Acad Dermatol Venereol. 2017 Mar;31(3):507-517. doi: 10.1111/jdv.14015. Epub 2016 Dec 19.