Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy (ADVANCE)

A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Mild to Moderate Plaque Psoriasis

This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with mild to moderate plaque psoriasis.

Approximately 574 subjects with mild to moderate plaque psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Other: Placebo; Drug: Apremilast

Detailed Description

The study will consist of four phases:

• Screening Phase - up to 35 days

• Double-blind Placebo-controlled Phase - Weeks 0 to 16

  - Subjects will be randomly assigned to either apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID.

• Apremilast Extension Phase - Weeks 16 to 32

  - All subjects will be switched to (or continue with) apremilast 30 mg BID. All subjects will maintain this dosing through Week 32.

• Observational Follow-up Phase - 4 weeks - Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue the study early.

• Study Type: Interventional
• Enrollment (Actual): 595
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Institute For Skin Advancement
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Chih-Ho Hong Medical, Inc.
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3CON2
      • Winnipeg Clinic Dermatology Research
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • SkinWise Dermatology
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Brunswick Dermatology Centre
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1A 4Y3
      • Karma Clinical Trials
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • SimcoDerm Medical and Surgical Dermatology Center
    • Guelph, Ontario, Canada, N1L 0B7
      • Guelph Dermatology Research
    • London, Ontario, Canada, N6H 5L5
      • DermEffects
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research
    • North Bay, Ontario, Canada, P1B 3Z7
      • North Bay Dermatology Centre
    • Peterborough, Ontario, Canada, K9J 5K2
      • Skin Center for Dermatology
    • Toronto, Ontario, Canada, M3H 5Y8
      • Toronto Research Centre
    • Toronto, Ontario, Canada, M4W 2N2
      • Sameh Hanna Medicine Professional Corporation DBA Dermatology on Bloor
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
    • Windsor, Ontario, Canada, N8W 5L7
      • Windsor Clinical Research Inc.
  • Quebec
    • Drummondville, Quebec, Canada, J2B 5L4
      • Dr Isabelle Delorme inc
    • Saint-Jerome, Quebec, Canada, J7Z 7E2
      • Dre Angelique Gagne-Henley M.D. Inc.
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Skinsense Medical Research
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Total Skin & Beauty Dermatology Center
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology Clinic
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center, PLLC / Hull Dermatology
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • San Diego, California, United States, 92123
      • TCR Medical Corporation
    • San Francisco, California, United States, 94118
      • University of California San Francisco Psoriasis and Skin Treatment Center
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Dermatology Clinic
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Total Vein and Skin, LLC
    • Coral Gables, Florida, United States, 33134
      • Florida Academic Centers Research and Education
    • Miami, Florida, United States, 33144
      • International Dermatology Research
    • Miami, Florida, United States, 33180
      • Center for Clinical and Cosmetic Research
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Tampa, Florida, United States, 33612
      • University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Atlanta Dermatology, Vein and Research Center, PC
    • Atlanta, Georgia, United States, 30328
      • Medical Dermatology Specialists, Inc. - Advanced Medical Research
    • Newnan, Georgia, United States, 30263
      • Medaphase Inc
    • Snellville, Georgia, United States, 30078
      • Gwinnett Clinical Research Center, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group, LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management LLC
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Lawrence Green, MD, LLC
    • Rockville, Maryland, United States, 20850
      • Derm Associates
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • ActivMed Practices & Research Inc
    • Boston, Massachusetts, United States, 02114-2517
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center - New Center One
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Central Dermatology
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • JDR Dermatology Research, LLC
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Psoriasis Treatment Center of Central New Jersey
  • New York
    • Bronx, New York, United States, 10467
      • Albert Einstein College Of Medicine - Montefiore Medical Center
    • New York, New York, United States, 10003
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
    • Fairborn, Ohio, United States, 45324
      • Wright State Physicians
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University - Lewis Katz School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Clinical Research Center of the Carolinas
  • Texas
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies
  • Utah
    • Murray, Utah, United States, 84107
      • University of Utah Midvalley Dermatology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research Inc
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Dermatology Center for Skin Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject must be male or female, ≥18 years of age at the time of signing the informed consent form (ICF).
2. Subject must have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF.
3. Subject must have a diagnosis of mild to moderate plaque psoriasis at both Screening and Baseline.
4. Subject must be inadequately controlled with or intolerant of at least one topical therapy at both Screening and Baseline.
5. Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.
6. Subject must meet laboratory criteria.
7. Subject has not had prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis, or any other condition that could impact the assessment of psoriasis.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subjects has 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.

2. Subject has hepatitis B surface antigen positive at Screening. 3. Subject has active tuberculosis (TB) or a history of incompletely treated TB.

4. Subject has history of positive human immunodeficiency virus (HIV), or has congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).

5. Subject has hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.

6. Subject has prior history of suicide attempt at any time in the subject's life time or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. 7. Subject has current or planned concurrent use of therapies that may have a possible effect on psoriasis during the course of the treatment phase of the trial.

8. Use of any investigational drug beginning 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

9. Subject had prior treatment with apremilast.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo-controlled Phase: Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Other: Placebo; Placebo, oral, twice daily
Experimental: Placebo-controlled Phase: Apremilast 30 mg; Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Drug: Apremilast; Apremilast, oral, twice daily
Experimental: Extension Phase: Apremilast 30 mg; Eligible participants who completed the placebocontrolled phase entered the extension phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).	Drug: Apremilast; Apremilast, oral, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 During the Placebo-Controlled Phase	The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation. An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16.	Baseline and Week 16 of the placebo-controlled phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥ 75 Percent (%) Improvement From Baseline in Affected Body Surface Area (BSA) at Week 16	The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Percentage of Affected BSA at Week 16	The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area). A negative change from baseline indicates a reduction of affected BSA.	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 16	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. 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. A negative change from baseline indicates an improvement of disease symptoms.	Baseline and Week 16 of the placebo-controlled phase
Percentage of Participants Who Achieved BSA ≤ 3% for Participants With Baseline Affected BSA > 3% at Week 16	The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).	Baseline and Week 16 of the placebo-controlled phase
Percentage of Participants With ≥ 4-point Reduction From Baseline in Whole Body Itch Numeric Rating Scale (NRS) Score at Week 16 Who Had Baseline Whole Body Itch NRS ≥ 4	The whole body itch NRS is a self-reported measure where participants were asked to assess whole body itch and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A reduction in score from baseline represents an improvement in symptoms.	Baseline and Week 16 of the placebo-controlled phase
Percentage of Participants With a Scalp Physician Global Assessment (ScPGA) Response at Week 16 Among Participants With Baseline scPGA Score ≥ 2 at Week 16	The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an Investigator's assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation of the overall scalp. An ScPGA response is defined as and ScPGA score clear (0) or almost clear (1) with at least a 2-point reduction from baseline among participants with a baseline ScPGA score ≥ 2.	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16	The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). 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), 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 0 (not at all), 1 (a little) and 2 (a lot). Total scores have a possible range of 0 to 30, with 30 corresponding to the worst health-related quality of life, and 0 corresponding to the best score. A negative change from baseline indicates an improvement in health-related quality of life scores.	Baseline and Week 16 of the placebo-controlled phase
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A TEAE is any AE that occurs following administration of study treatment. Frequency of TEAEs was assessed as well as severity and treatment relatedness. A TEAE was considered severe based on the Investigator's assessment. A TEAE could be severe if it was serious or non-serious, had symptoms causing discomfort or pain, requiring medical or surgical attention or intervention, interfered with activities of daily life and if drug therapy was required.	Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Stein Gold L, Papp K, Pariser D, Green L, Bhatia N, Sofen H, Albrecht L, Gooderham M, Chen M, Paris M, Wang Y, Callis Duffin K. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2022 Jan;86(1):77-85. doi: 10.1016/j.jaad.2021.07.040. Epub 2021 Jul 31.
• Mease PJ, Hatemi G, Paris M, Cheng S, Maes P, Zhang W, Shi R, Flower A, Picard H, Stein Gold L. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behcet's Syndrome. Am J Clin Dermatol. 2023 Sep;24(5):809-820. doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): March 6, 2020
• Study Completion (Actual): July 24, 2020

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Double-Blind; Plaque Psoriasis; Scalp; CC-10004; Apremilast; Otezla; Itch; Phase 3; Moderate; Nail; Mild
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-PSOR-022; U1111-1218-8372 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No