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

Psoriasis Clinical Trial

— ADVANCE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03721172
• Other study ID #: CC-10004-PSOR-022
• Secondary ID: U1111-1218-8372
• Status: Completed
• Phase: Phase 3
• Start date: March 11, 2019
• Est. completion date: July 24, 2020

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 595
• Est. completion date: July 24, 2020
• Est. primary completion date: March 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Apremilast
Apremilast, oral, twice daily

Other:
• Placebo
Placebo, oral, twice daily

Locations

Country	Name	City	State
Canada	SimcoDerm Medical and Surgical Dermatology Center	Barrie	Ontario
Canada	Institute for Skin Advancement	Calgary	Alberta
Canada	Dr Isabelle Delorme inc	Drummondville	Quebec
Canada	Stratica Medical	Edmonton	Alberta
Canada	Brunswick Dermatology Centre	Fredericton	New Brunswick
Canada	Guelph Dermatology Research	Guelph	Ontario
Canada	DermEffects	London	Ontario
Canada	Lynderm Research	Markham	Ontario
Canada	North Bay Dermatology Centre	North Bay	Ontario
Canada	Skin Center for Dermatology	Peterborough	Ontario
Canada	Karma Clinical Trials	Saint John's	Newfoundland and Labrador
Canada	Dre Angelique Gagne-Henley M.D. Inc.	Saint-Jerome	Quebec
Canada	Skinsense Medical Research	Saskatoon	Saskatchewan
Canada	Chih-Ho Hong Medical, Inc.	Surrey	British Columbia
Canada	Enverus Medical Research	Surrey	British Columbia
Canada	Sameh Hanna Medicine Professional Corporation DBA Dermatology on Bloor	Toronto	Ontario
Canada	Toronto Research Centre	Toronto	Ontario
Canada	K. Papp Clinical Research	Waterloo	Ontario
Canada	Windsor Clinical Research Inc.	Windsor	Ontario
Canada	SkinWise Dermatology	Winnipeg	Manitoba
Canada	Winnipeg Clinic Dermatology Research	Winnipeg	Manitoba
United States	Atlanta Dermatology, Vein and Research Center, PC	Alpharetta	Georgia
United States	Medical Dermatology Specialists, Inc. - Advanced Medical Research	Atlanta	Georgia
United States	University of Colorado Hospital - Dermatology Clinic	Aurora	Colorado
United States	ActivMed Practices & Research Inc	Beverly	Massachusetts
United States	Total Skin & Beauty Dermatology Center	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Total Vein and Skin, LLC	Boynton Beach	Florida
United States	Albert Einstein College of Medicine - Montefiore Medical Center	Bronx	New York
United States	Clinical Research Center of the Carolinas	Charleston	South Carolina
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Florida Academic Centers Research and Education	Coral Gables	Florida
United States	Henry Ford Medical Center - New Center One	Detroit	Michigan
United States	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	Wright State Physicians	Fairborn	Ohio
United States	Johnson Dermatology Clinic	Fort Smith	Arkansas
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	Clinical Partners, LLC	Johnston	Rhode Island
United States	JDR Dermatology Research, LLC	Las Vegas	Nevada
United States	Dermatology Research Associates	Los Angeles	California
United States	Clinical Trials Management LLC	Metairie	Louisiana
United States	Center for Clinical and Cosmetic Research	Miami	Florida
United States	International Dermatology Research	Miami	Florida
United States	Dermatology Center for Skin Health	Morgantown	West Virginia
United States	University of Utah MidValley Dermatology	Murray	Utah
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	MedaPhase INC	Newnan	Georgia
United States	Virginia Clinical Research Inc	Norfolk	Virginia
United States	Renstar Medical Research	Ocala	Florida
United States	Austin Institute for Clinical Research	Pflugerville	Texas
United States	Temple University - Lewis Katz School of Medicine	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Derm Associates	Rockville	Maryland
United States	Lawrence Green, MD, LLC	Rockville	Maryland
United States	Northwest Arkansas Clinical Trials Center, PLLC / Hull Dermatology	Rogers	Arkansas
United States	Central Dermatology	Saint Louis	Missouri
United States	TCR Medical Corporation	San Diego	California
United States	University of California San Francisco Psoriasis and Skin Treatment Center	San Francisco	California
United States	Clinical Science Institute	Santa Monica	California
United States	Gwinnett Clinical Research Center, Inc.	Snellville	Georgia
United States	University of South Florida - Carol and Frank Morsani Center for Advanced Health Care	Tampa	Florida
United States	Center for Clinical Studies	Webster	Texas
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,  Canada, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)

External Links

•   AmgenTrials clinical trials website