Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis.

Phase 3

Completed

Conditions: Plaque Psoriasis

Interventions: Drug: Apremilast
Drug: Placebo
Other: Topical or Phototherapy Therapy

Registration Number: NCT01232283

Lead Sponsor: Amgen

Brief Summary: This study will evaluate the effects of an experimental (being tested) study drug called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study is to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study will test efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 413

Inclusion Criteria

Males or females, ≥ 18 years of age at the time of signing the informed consent document
Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

a. Have moderate to severe plaque psoriasis at Screening and Baseline
Must meet all laboratory criteria
Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication
Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication.

Exclusion Criteria

Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.
Pregnant or breast feeding
History of allergy to any component of the study drug
Hepatitis B surface antigen positive at Screening
Anti-hepatitis C antibody positive at Screening
Active tuberculosis (TB) or a history of incompletely treated TB
Clinically significant abnormality on 12-Lead ECG at Screening
Clinically significant abnormal chest x-ray
History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency
Active substance abuse or a history of substance abuse within 6 months prior to Screening
Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening
Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] 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
Evidence of skin conditions that would interfere with clinical assessments
Topical therapy within 2 weeks of randomization
Systemic therapy for psoriasis within 4 weeks prior to randomization
Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)
Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization
Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization
Use of any investigational drug within 4 weeks prior to randomization
Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
Prior treatment with apremilast

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apremilast	Apremilast	Participants were initially randomized 2:1 and received apremilast 30 mg twice a day (BID). Participants maintained dosing through Week 32. At Week 32, responders, those with a Psoriasis Area Severity Index response -≥75 (PASI-75) and partial responders (≥PASI-50) were re-randomized 1:1 to apremilast 30 mg BID or matching placebo (treatment withdrawal). Participants could resume apremilast 30 mg BID at the time of loss of 50% of improvement in PASI score response which was observed at Week 32 compared to baseline), and no later than Week 52. At Week 52, the non-responders (\<PASI-50) had the option of adding topical therapies and/or phototherapy to their treatment regimen. Those re-randomized to apremilast 30 mg BID continued dosing through Week 52. At Week 52, participants continued treatment with apremilast 30 mg BID.
Apremilast	Placebo	Participants were initially randomized 2:1 and received apremilast 30 mg twice a day (BID). Participants maintained dosing through Week 32. At Week 32, responders, those with a Psoriasis Area Severity Index response -≥75 (PASI-75) and partial responders (≥PASI-50) were re-randomized 1:1 to apremilast 30 mg BID or matching placebo (treatment withdrawal). Participants could resume apremilast 30 mg BID at the time of loss of 50% of improvement in PASI score response which was observed at Week 32 compared to baseline), and no later than Week 52. At Week 52, the non-responders (\<PASI-50) had the option of adding topical therapies and/or phototherapy to their treatment regimen. Those re-randomized to apremilast 30 mg BID continued dosing through Week 52. At Week 52, participants continued treatment with apremilast 30 mg BID.
Apremilast	Topical or Phototherapy Therapy	Participants were initially randomized 2:1 and received apremilast 30 mg twice a day (BID). Participants maintained dosing through Week 32. At Week 32, responders, those with a Psoriasis Area Severity Index response -≥75 (PASI-75) and partial responders (≥PASI-50) were re-randomized 1:1 to apremilast 30 mg BID or matching placebo (treatment withdrawal). Participants could resume apremilast 30 mg BID at the time of loss of 50% of improvement in PASI score response which was observed at Week 32 compared to baseline), and no later than Week 52. At Week 52, the non-responders (\<PASI-50) had the option of adding topical therapies and/or phototherapy to their treatment regimen. Those re-randomized to apremilast 30 mg BID continued dosing through Week 52. At Week 52, participants continued treatment with apremilast 30 mg BID.
Placebo	Placebo	Participants will be initially randomized to placebo, identically matching during Weeks 0-16. At Week 16, Placebo participants will be switched to receive apremilast 30 mg BID. All participants will maintain Apremilast dosing through Week 32. At Week 32, participants originally randomized to placebo at baseline (Week 0) and are considered non-responders i( \< PASI-50) will have the option of adding topical therapies and/or phototherapy to their Apremilast treatment regimen. At Week 52, all participants will continue treatment with apremilast 30 mg BID. Participants will be followed and evaluated for safety and efficacy for up to an additional 4 years (years 2 through 5).
Placebo	Topical or Phototherapy Therapy	Participants will be initially randomized to placebo, identically matching during Weeks 0-16. At Week 16, Placebo participants will be switched to receive apremilast 30 mg BID. All participants will maintain Apremilast dosing through Week 32. At Week 32, participants originally randomized to placebo at baseline (Week 0) and are considered non-responders i( \< PASI-50) will have the option of adding topical therapies and/or phototherapy to their Apremilast treatment regimen. At Week 52, all participants will continue treatment with apremilast 30 mg BID. Participants will be followed and evaluated for safety and efficacy for up to an additional 4 years (years 2 through 5).
Placebo	Apremilast	Participants will be initially randomized to placebo, identically matching during Weeks 0-16. At Week 16, Placebo participants will be switched to receive apremilast 30 mg BID. All participants will maintain Apremilast dosing through Week 32. At Week 32, participants originally randomized to placebo at baseline (Week 0) and are considered non-responders i( \< PASI-50) will have the option of adding topical therapies and/or phototherapy to their Apremilast treatment regimen. At Week 52, all participants will continue treatment with apremilast 30 mg BID. Participants will be followed and evaluated for safety and efficacy for up to an additional 4 years (years 2 through 5).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline	Baseline to 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 is 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 is missing.

Secondary Outcome Measures

Name	Time	Method
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 From Baseline	Baseline to Week 16	The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), 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 must have factored 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 was 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.
Percent Change From Baseline in the Affected Body Surface Area (BSA) at Week 16	Baseline and Week 16	BSA was 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 (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100\*(visit BSA - baseline BSA) / baseline BSA (%).
Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16	Baseline and Week 16	Psoriasis Area Severity Index (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 total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing.
Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline	Baseline and 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 improvement in PASI score was used as a measure of efficacy. The PASI is 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 is missing.
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260	Week 0 to Week 260; The mean duration of exposure was 100.66 weeks.	The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure phase. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.
Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16	Baseline and Week 16	The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Participant's Assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value - baseline value.
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16	Baseline and 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 subject 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 was 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.
Change From Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16	Baseline to Week 16	The SF-36 was a 36-item general health 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. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value.
Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline	Baseline to 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. See Outcome measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See Outcome Measure #2 for further description.
Time to Loss of Effect (Loss of 50% Improvement in PASI Score Obtained at Week 32 Compared to Baseline) During the Randomized Treatment Withdrawal Phase	Weeks 32 to Week 52	Time to loss was the time between the re-randomization date and the date of the first assessment with loss of 50% PASI improvement (event), or the time between the re-randomization date and the date of the last PASI assessment in the randomized withdrawal phase prior to addition of topical/phototherapy or other effective psoriasis therapies, or resumption of apremilast 30 mg BID, or discontinuation, or Week 52 if no loss (censored), whichever was earlier
Number of Participants With Psoriasis Flare or Rebound in the Apremilast-Exposure Period	Week 0 to Week 260	Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. \[1\] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. \[2\] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. \[3\] PASI \>= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in \[1\] and/or \[2\].
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in the Placebo Controlled Phase	Baseline to Week 16	An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant'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) was considered an AE. A serious AE (SAE) is any untoward adverse event 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 the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.
Number of Participants With Psoriasis Flare or Rebound in the Placebo Controlled Phase	Week 0 to Week 16	Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. \[1\] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. \[2\] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. \[3\] PASI \>= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in \[1\] and/or \[2\].

Trial Locations

Locations (45): Clinical Science Institute
🇺🇸
Santa Monica, California, United States
Northwestern University Northwestern Medical Faculty Foundation
🇺🇸
Chicago, Illinois, United States
Radiant Research, Inc.
🇺🇸
Anderson, South Carolina, United States
Florida Academic Dermatology Center
🇺🇸
Miami, Florida, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Hospital Universitario La Princesa
🇪🇸
Madrid, Spain
Modern Research Associates PLLC
🇺🇸
Dallas, Texas, United States
Northwest Dermatology and Laser Centre
🇨🇦
Calgary, Alberta, Canada
Clinical Partners, LLC
🇺🇸
Johnston, Rhode Island, United States
Arizona Skin and Laser Therapy Inst., Ltd.
🇺🇸
Phoenix, Arizona, United States
Hospital Abente y Lago
🇪🇸
La Coruna, Spain
PMG Research of Winston-Salem
🇺🇸
Winston-Salem, North Carolina, United States
Virginia Medical Research
🇺🇸
Norfolk, Virginia, United States
Burke Pharmaceutical Research
🇺🇸
Hot Springs, Arkansas, United States
NewLab Clinical Research
🇨🇦
St. John's, Newfoundland and Labrador, Canada
Larrey University Hospital
🇫🇷
Toulouse, France
Bakersfield Dermatology and Skin Cancer Medical Group
🇺🇸
Bakersfield, California, United States
Advanced Medical Research
🇺🇸
Atlanta, Georgia, United States
Q & T Research Sherbrooke Inc.
🇨🇦
Sherbrooke, Quebec, Canada
Dr. med. Beatrice Gerlach
🇩🇪
Dresden, Germany
Austin Dermatology Associates
🇺🇸
Austin, Texas, United States
MedaPhase Inc.
🇺🇸
Newnan, Georgia, United States
Dermatology Research Associates
🇺🇸
Los Angeles, California, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Stratica Medical
🇨🇦
Edmonton, Alberta, Canada
Hopitaux Universitaires de Geneve-HUG
🇨🇭
Geneva, Switzerland
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona (Barcelona), Spain
Hospital haut leveque
🇫🇷
Pessac, France
Centre d'lnvestigation Clinique, Hopital Jean Minjoz
🇫🇷
Besancon, France
Medizinische Universitat Wien, Universitatsklinik fur Dermatologie. Abteilung fur Immundermatologie
🇦🇹
Vienna, Austria
Windsor Clinical Research Inc.
🇨🇦
Winsor, Ontario, Canada
Skin Center for Dermatology
🇨🇦
Peterborough, Ontario, Canada
Istituto Dermatologico San Gallicano IRCCS Dermatologia Clinica
🇮🇹
Rome, Italy
Universitäts-Hautklinik Kiel
🇩🇪
Kiel, Germany
Bispebjerg Hospital
🇩🇰
Copenhagen, Denmark
A.O.U. Integrata di Verona Universitá degli Studi di Verona Sezione di Dermatologia e Venerologia
🇮🇹
Verona, Italy
Hautarztpraxis Mahlow
🇩🇪
Mahlow, Germany
Universitatsklinikum Leipzig
🇩🇪
Leipzig, Germany
Center for Clinical Studies
🇺🇸
Webster, Texas, United States
Centre de Recherche Dermatologique du Quebec Metropolitain CRDQ
🇨🇦
Quebec, Canada
Universitatsklinikum Hamburg-Eppendorf / IVDP
🇩🇪
Hamburg, Germany
Hospital Universitario Fundacion Alcorcon
🇪🇸
Alcorcón, Spain
Universita degli Studi di Napoli Federico II
🇮🇹
Napoli, Italy
University of Zurich Hospital
🇨🇭
Zurich, Switzerland
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain