Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis

Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01690299
• Other study ID #: CC-10004-PSOR-010
• Secondary ID: 2012-000859-14
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2012
• Est. completion date: April 4, 2016

Study information

• Verified date: April 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: April 4, 2016
• Est. primary completion date: July 3, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriasis
• Psoriatic Arthritis

Intervention

Drug:
• Apremilast
Apremilast 30 mg tablet orally BID
• Etanercept
Etanercept 50 mg evaluator/subject-blinded SC QW injection
• Placebo tablet
Placebo tablets BID
• Placebo injection
Once weekly evaluator/subject-blinded SC placebo (1 mL x 2 injections SC)

Locations

Country	Name	City	State
Australia	The Skin Centre	Benowa	Queensland
Australia	Sinclair Dermatology	East Melbourne	Victoria
Australia	Fremantle Dermatology	Fremantle	Western Australia
Australia	Gairdner Hospital	Victoria Park
Australia	Rheumatology unit Ward 5C Queen Elizabeth Hospital	Woodville
Australia	Veracity Clinical Research	Woolloongabba
Belgium	Cliniques Universitaires St-Luc	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	University Hospital of Liege CHU Liege	Liege
Canada	Eastern Canada Cutaneous Research Associates Ltd	Halifax	Nova Scotia
Canada	Siena Medical Research	Montreal	Quebec
Canada	Skin Center for Dermatology	Peterborough	Ontario
Canada	Q & T Research Sherbrooke Inc.	Sherbrooke	Quebec
Canada	K. Papp Clinical Research Inc.	Waterloo	Ontario
Czechia	Dorothea, Kožní a korektivne dermatologické pracovište	Chomutov
Czechia	Dermamedica	Nachod
Czechia	Krajská nemocnice Pardubice, Kožní oddelení	Pardubice
Czechia	Východoceské dermatologické centrum Homea s.r.o.	Pardubice
Czechia	Dermatovenerologicka ambulance	Svitavy
Czechia	Koznia zilni ambulance	Ústí nad Labem
Estonia	South Estonian Hospital Ltd	Meegomäe Village, Võru County
Estonia	Dermatology Clinic of Tartu University Hospital	Tartu
Germany	Dermatologische Praxis	Berlin
Germany	Klinische Forschung Berlin - Buch GmbH	Berlin
Germany	Psoriasis Study Center	Berlin
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	Hautklinik Universitatsklinikum Erlangen	Erlangen
Germany	University Hospital Frankfurt	Frankfurt
Germany	Institute for Health Services Research in Dermatology and Nursing - IVDP, University Medical Center	Hamburg
Germany	SCIderm GmbH	Hamburg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	UniversitatsKlinikum Leipzig A.o.R.	Leipzig
Germany	Comprehensive Center of Inflammatory Medicine (CCIM) University Medical Center Schleswig-Holstein	Lübeck
Germany	Gemeinschaftspraxis Mahlow	Mahlow
Germany	University Hospital Munster	Münster
Germany	Praxis fr Dermatologie und Venerologie	Wuppertal
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszárd
Hungary	Allergo-Derm Bakos Kft.	Szolnok
Latvia	LTD M & M centrs	Adazi
Latvia	Arija's Ancane's Family Doctor Private Practice	Baldone
Latvia	Adoria Ltd	Riga
Latvia	Family Doctor's Indra's Kenina's Practice	Riga
Latvia	Riga 1st Hospital Skin and Sexually Transmitted Diseases Clinical Centre	Riga
Latvia	Health Center of Talsi Ltd	Talsi
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Radboud University Medical Centre	Nijmegen
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Leeds Teaching Hospitals Trust	Leeds
United Kingdom	St Helier Hospital	London
United Kingdom	Whipps Cross University Hospital	London
United Kingdom	George Eliot Hospital	Nuneaton
United States	Atlanta Dermatology, Vein and Research Center, PC	Alpharetta	Georgia
United States	Teckton Research	Austin	Texas
United States	Bakersfield Dermatology and Skin Cancer Medical Group	Bakersfield	California
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Horizons Clinical Research	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Forest Hills Dermatology Group	Forest Hills	New York
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	University of California Irvine-Department of Dermatology	Irvine	California
United States	Florida Center for Dermatology, PA	Jacksonville	Florida
United States	Dermatology and Advanced Aesthetics	Lake Charles	Louisiana
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	The Education and Research Foundation	Lynchburg	Virginia
United States	Florida Academic Dermatology Center	Miami	Florida
United States	International Dermatology Research	Miami	Florida
United States	Tennesse Clinical Research Center	Nashville	Tennessee
United States	NYU Department of Dermatology	New York	New York
United States	Virginia Clinical Research Inc	Norfolk	Virginia
United States	Renstar Medical Research	Ocala	Florida
United States	Arizona Research Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Lawrence Green, MD, LLC	Rockville	Maryland
United States	University of California San Diego Medical Center	San Diego	California
United States	Dermatology Associates of Seattle	Seattle	Washington
United States	NorthShore University HealthSystem	Skokie	Illinois
United States	Robert Wood Johnson Medical School	Somerset	New Jersey
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	George Washington University	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Estonia,  Germany,  Hungary,  Latvia,  Netherlands,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.	Baseline to Week 16
Secondary	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	PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.	Baseline and Week 16
Secondary	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	The sPGA is an assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator should factor in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign is averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.	Baseline and Week 16
Secondary	Percent Change From Baseline in the Affected Body Surface Area (BSA) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16	BSA is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline was determined at each visit of the study, and is calculated as 100*(post-baseline BSA - baseline BSA) / baseline BSA.	Baseline to Week 16
Secondary	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	PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.	Baseline to Week 16
Secondary	Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score In Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16	DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being "A lot," "A little," or "Not at all" (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.	Baseline to Week 16
Secondary	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	The SF-36 is a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Scores from the 8 scales were transformed to the norm-based scores using weights from U.S. general population to have a mean of 50 and variance = 10, with higher scores indicating better health. From these 8 scale, two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS), both having the same mean of 50 and variance = 10 as noted for the individual scales for the U.S. general population, and with higher scores indicating better health. For MCS, change from baseline was calculated, where change = visit value - baseline value.	Baseline to Week 16
Secondary	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	The Lattice System Physician's Global Assessment is a global assessment performed by the investigator of psoriasis severity. Integrating ranges of BSA involvement with assessments of overall plaque severity (using a 4 point scale from none to marked for the signs of plaque elevation, erythema and scale), the LS-PGA produces an overall assessment of psoriasis severity on an 8-point scale, ranging from clear to very severe. To determine the final score, the lattice portion is governed by the BSA and among the plaque qualities, weights plaque elevation as most important, erythema next, and scale least.	Baseline to Week 16
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Phase	A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug for participants who discontinued early. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the patient's health, including laboratory test values, regardless of etiology. Any worsening (ie, clinically significant adverse change in frequency or intensity of a preexisting condition) should be considered an AE. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above.	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
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-exposure Period	A TEAE in the apremilast-exposure phase is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes listed above.	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
Secondary	Psoriasis Flare/Rebound	Psoriasis flare is an AE and represents an atypical or unusual worsening of disease during treatment. It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is an AE and is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. This exacerbation is characterized by a PASI =125% of baseline or a new generalized pustular, erythrodermic, or more inflammatory psoriasis after stopping therapy.	Week 0 to Week 16; Placebo controlled phase
Secondary	Psoriasis Flare/Rebound	Psoriasis flare is an AE and represents an atypical or unusual worsening of disease during treatment. It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is an AE and is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. This exacerbation is characterized by a PASI =125% of baseline or a new generalized pustular, erythrodermic, or more inflammatory psoriasis after stopping therapy. PASI =125% of baseline score at any visit after the last dose date for those who discontinued within the phase.	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.