A Phase 4 Study of Efficacy and Safety of Apremilast in Subjects With Moderate Plaque Psoriasis. (UNVEIL)

• ClinicalTrials.gov Identifier: NCT02425826
• Recruitment Status: Completed
• First Posted: April 24, 2015
• Results First Posted: June 6, 2017
• Last Update Posted: March 15, 2022
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

This study will evaluate the clinical efficacy, the patients quality of life, and safety of oral apremilast 30 mg twice daily (BID) compared to placebo, in adult patients with moderate plaque psoriasis during the 16 week Placebo controlled Phase and then upto 1 year in the Extension Phase of the trial.

Condition or disease	Intervention/treatment	Phase
Parapsoriasis	Drug: Apremilast; Drug: Placebo; Drug: Placebo-Apremilast	Phase 4

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Detailed Description:

This is a Phase 4, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast in subjects with moderate plaque psoriasis. 221 participants were randomized 2 (apremilast):1 (placebo) at approximately 25 sites in the United States. Those randomized to the apremilast treatment group received apremilast 30 mg tablets orally twice daily for 52 weeks. Those randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally twice daily (BID) for 16 weeks. Beginning Week 16, those initially randomized to placebo were switched to receive apremilast 30 mg BID for an additional 36 weeks (52 weeks total).

Study enrolled adult patients with stable moderate plaque psoriasis, who are naïve to systemic psoriasis treatments.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Multicenter, Randomized, Placebo-controlled, Double-blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate Plaque Psoriasis
• Actual Study Start Date: April 20, 2015
• Actual Primary Completion Date: February 12, 2016
• Actual Study Completion Date: November 22, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Apremilast; Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.	Drug: Apremilast; Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.; Other Name: CC-10004, Otzela; Drug: Placebo; Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.; Drug: Placebo-Apremilast; At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total); Other Names: Otezla; CC-10004
Placebo Comparator: Placebo; Placebo tablets BID during Weeks 0 to 16; at week 16, placebo participants were switched to apremilast 30 mg tablets BID for 36 weeks (from week 16 to week 52)	Drug: Placebo; Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.; Drug: Placebo-Apremilast; At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total); Other Names: Otezla; CC-10004

Outcome Measures

Primary Outcome Measures :

1. Mean Percentage Change From Baseline in the Product of BSA (%) and the sPGA Which is Considered as the Total Psoriasis Severity Index at Week 16 [ Time Frame: Baseline to Week 16 (end of phase) ]
   BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. The range of BSA*sPGA mean percentage change from baseline to week 16 (end of phase) were -100 to 344.4 and -100 to 100 for the placebo and apremilast groups respectively. Higher scores represented worse outcomes.

Secondary Outcome Measures :

1. Mean Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 [ Time Frame: Baseline to Week 16 (end of phase) ]
   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.
2. Percentage of Participants Who Achieved a sPGA Score of Clear (0) or Almost Clear (1) at Week 16 From Baseline [ Time Frame: Baseline to Week 16 (end of phase) ]
   The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score.
3. Percentage of Participants Who Achieved a Clear (0) or Very Mild (1) on Patient Global Assessment (PtGA) Scale at Week 16 From Baseline [ Time Frame: Baseline to Week 16 (end of phase) ]
   The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe).
4. Mean Change From Baseline in Pruritus Visual Analog Scale (VAS) [ Time Frame: Baseline to Weeks 1 and 16 (end of phase) ]
   The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom.
5. Percentage of Participants With Scalp Psoriasis Who Achieved a Clear (0) or Minimal (1) on Scalp Physician's Global Assessment (ScPGA) Scale at Week 16. [ Time Frame: Baseline to Week 16 (end of phase) ]
   The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline.
6. Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 16 [ Time Frame: Baseline to Week 16 (end of phase) ]
   The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment.
7. Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 52 [ Time Frame: Baseline to week 52 ]
   The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment.
8. Mean Percentage Change From Baseline in Psoriasis Area Severity Index Score (PASI) at Week 16 [ Time Frame: Baseline to Week 16 (end of phase) ]
   The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
9. Percentage of Participants Who Achieved at Least a 50% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-50 From Baseline at Week 16. [ Time Frame: Baseline to Week 16 (end of phase) ]
   The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
10. Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-75 From Baseline at Week 16 [ Time Frame: Baseline to Week 16 (end of phase) ]
    The PASI score 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
11. Mean Percentage Change From Baseline in the Product of BSA (%) x sPGA at Week 52 [ Time Frame: Baseline to Week 52 ]
    BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score.
12. Percentage of Participants With Scalp Psoriasis Who Were Initially Randomized to Apremilast and Maintained the Scalp Physician's Global Assessment (ScPGA) Response From Week 16 to Week 52. [ Time Frame: Week 16 to Week 52 ]
    The ScPGA will assess scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment with scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA is restricted to the participants with scalp involvement at baseline.
13. Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase [ Time Frame: From first dose of study drug to Week 16; maximum duration of exposure was 20.1 weeks during placebo controlled phase ]
    Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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.
14. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) During the Apremilast-Exposure Phase [ Time Frame: Date of first dose of apremilast during the placebo controlled phase or date of first dose of apremilast after week 16; overall maximum duration of exposure was 61.5 weeks during apremilast-exposure phase ]
    Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Males or females, ≥ 18 years of age at the time of signing the informed consent document.
2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the informed consent.

5. Have moderate plaque psoriasis at screening and baseline as defined by

   1. BSA (Body Surface Area)5% to 10% and
   2. sPGA (Physician's Global Assessment) 3 (moderate) based on a 0 to 5 point scale
6. Must be in general good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, and clinical laboratories.
7. No prior exposure to systemic treatments or biologics for the treatment of psoriatic arthritis, psoriasis, or any other indication that could impact the assessment of psoriasis.
8. Females of childbearing potential (FCBP)must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
9. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product

Exclusion Criteria:

1. Other than psoriasis, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,immunologic disease, or other major disease that is currently uncontrolled.
2. 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.
3. Any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, guttate, inverse, or pustular psoriasis), other than plaque psoriasis.
4. Prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
5. Pregnant or breast feeding.
6. Active substance abuse or a history of substance abuse within 6 months prior to signing the informed consent.

7. Malignancy or history of malignancy, except for:

   1. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
   2. treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of signing the informed consent.
8. Topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol). Use of phototherapy within 4 weeks prior to randomization.
9. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
10. Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study.
11. Prior treatment with apremilast.

Contacts and Locations

Locations

United States, Alabama

UAB at Birmingham - The Kirklin Clinic

Birmingham, Alabama, United States, 35233

United States, California

Center For Dermatology

Fremont, California, United States, 94538

Dermatology Research Associates

Los Angeles, California, United States, 90045

Blue Harbor Dermatology

Newport Beach, California, United States, 92663

Center for Dermatology and Laser Surgery

Sacramento, California, United States, 95819

East Bay Rheumatology Medical

San Leandro, California, United States, 94578

Tien Q. Nguyen MD Inc

Tustin, California, United States, 92780

United States, Connecticut

UConn Health Center

Farmington, Connecticut, United States, 06030

United States, Florida

Dermatology Associates

Panama City, Florida, United States, 32405-4542

USF Health Faculty Office Building-FOB

Tampa, Florida, United States, 33612

Forward Clinical Trials Inc

Tampa, Florida, United States, 33624

United States, Georgia

Dermatologic Surgery Specialists, P.C.

Macon, Georgia, United States, 31217

United States, Indiana

Shideler Clinical Research Center

Carmel, Indiana, United States, 46032

United States, Kentucky

Dermatology Specialists, PSC

Louisville, Kentucky, United States, 40202

DermResearch, PLLC

Louisville, Kentucky, United States, 40217

United States, Maryland

Lawrence Green, MD, LLC

Rockville, Maryland, United States, 20850

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

United States, Nevada

Las Vegas Skin and Cancer Clinics

Las Vegas, Nevada, United States, 89052

United States, New Jersey

Psoriasis Treatment Center of Central New Jersey

East Windsor, New Jersey, United States, 08520

United States, New York

Garden City Dermatology

Garden City, New York, United States, 11530

Sadick Research Group

New York, New York, United States, 10075

Dermatology Associates of Rochester PC

Rochester, New York, United States, 14623

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267-0501

United States, South Carolina

Dermatology and Laser Center of Charleston

Charleston, South Carolina, United States, 29414

United States, Utah

University of Utah School of Medicine

Salt Lake City, Utah, United States, 84132

United States, Virginia

Dermatology Consultants, Inc.

Lynchburg, Virginia, United States, 24501

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stein Gold L, Bagel J, Lebwohl M, Jackson JM, Chen R, Goncalves J, Levi E, Duffin KC. Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL. J Drugs Dermatol. 2018 Feb 1;17(2):221-228.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02425826
• Obsolete Identifiers: NCT02555826
• Other Study ID Numbers: CC-10004-PSOR-012
• First Posted: April 24, 2015
• Results First Posted: June 6, 2017
• Last Update Posted: March 15, 2022
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: http://www.amgen.com/datasharing

Keywords provided by Amgen:

Parapsoriasis; Plaque Psoriasis; CC-10004; Apremilast; Moderate Plaque Psoriasis; Safety

Additional relevant MeSH terms:

Psoriasis; Parapsoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Thalidomide; Apremilast; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Leprostatic Agents; Anti-Bacterial Agents; Anti-Infective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents