Clinical trial NCT03721172: Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Keywords: Phase 3
Double-Blind
Efficacy
Safety
Apremilast
Otezla
CC-10004
Plaque Psoriasis
Mild
Moderate
Scalp
Nail
Itch
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-10-26
Enrollment: 595
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 During the Placebo-Controlled Phase
timeFrame: Baseline and Week 16 of the placebo-controlled phase
Secondary outcomes:
measure: Percentage of Participants With a ≥ 75 Percent (%) Improvement From Baseline in Affected Body Surface Area (BSA) at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Change From Baseline in Percentage of Affected BSA at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Change From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Percentage of Participants Who Achieved BSA ≤ 3% for Participants With Baseline Affected BSA > 3% at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: 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
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Percentage of Participants With a Scalp Physician Global Assessment (ScPGA) Response at Week 16 Among Participants With Baseline scPGA Score ≥ 2 at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16
timeFrame: Baseline and Week 16 of the placebo-controlled phase
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Total Skin & Beauty Dermatology Center
state: Alabama
city: Fort Smith
country: United States
facility: Johnson Dermatology Clinic
state: Arkansas
city: Rogers
country: United States
facility: Northwest Arkansas Clinical Trials Center, PLLC / Hull Dermatology
state: Arkansas
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: San Diego
country: United States
facility: TCR Medical Corporation
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Psoriasis and Skin Treatment Center
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Dermatology Clinic
state: Colorado
city: Boynton Beach
country: United States
facility: Total Vein and Skin, LLC
state: Florida
city: Coral Gables
country: United States
facility: Florida Academic Centers Research and Education
state: Florida
city: Miami
country: United States
facility: International Dermatology Research
state: Florida
city: Miami
country: United States
facility: Center for Clinical and Cosmetic Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
state: Florida
city: Alpharetta
country: United States
facility: Atlanta Dermatology, Vein and Research Center, PC
state: Georgia
city: Atlanta
country: United States
facility: Medical Dermatology Specialists, Inc. - Advanced Medical Research
state: Georgia
city: Newnan
country: United States
facility: MedaPhase INC
state: Georgia
city: Snellville
country: United States
facility: Gwinnett Clinical Research Center, Inc.
state: Georgia
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Metairie
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Rockville
country: United States
facility: Derm Associates
state: Maryland
city: Rockville
country: United States
facility: Lawrence Green, MD, LLC
state: Maryland
city: Beverly
country: United States
facility: ActivMed Practices & Research Inc
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center - New Center One
state: Michigan
city: Fridley
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Saint Louis
country: United States
facility: Central Dermatology
state: Missouri
city: Las Vegas
country: United States
facility: JDR Dermatology Research, LLC
state: Nevada
city: East Windsor
country: United States
facility: Psoriasis Treatment Center of Central New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein College of Medicine - Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Fairborn
country: United States
facility: Wright State Physicians
state: Ohio
city: Philadelphia
country: United States
facility: Temple University - Lewis Katz School of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Johnston
country: United States
facility: Clinical Partners, LLC
state: Rhode Island
city: Charleston
country: United States
facility: Clinical Research Center of the Carolinas
state: South Carolina
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Murray
country: United States
facility: University of Utah MidValley Dermatology
state: Utah
city: Norfolk
country: United States
facility: Virginia Clinical Research Inc
state: Virginia
city: Morgantown
country: United States
facility: Dermatology Center for Skin Health
state: West Virginia
city: Calgary
country: Canada
facility: Institute for Skin Advancement
state: Alberta
city: Edmonton
country: Canada
facility: Stratica Medical
state: Alberta
city: Surrey
country: Canada
facility: Chih-Ho Hong Medical, Inc.
state: British Columbia
city: Surrey
country: Canada
facility: Enverus Medical Research
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Clinic Dermatology Research
state: Manitoba
city: Winnipeg
country: Canada
facility: SkinWise Dermatology
state: Manitoba
city: Fredericton
country: Canada
facility: Brunswick Dermatology Centre
state: New Brunswick
city: Saint John's
country: Canada
facility: Karma Clinical Trials
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: SimcoDerm Medical and Surgical Dermatology Center
state: Ontario
city: Guelph
country: Canada
facility: Guelph Dermatology Research
state: Ontario
city: London
country: Canada
facility: DermEffects
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research
state: Ontario
city: North Bay
country: Canada
facility: North Bay Dermatology Centre
state: Ontario
city: Peterborough
country: Canada
facility: Skin Center for Dermatology
state: Ontario
city: Toronto
country: Canada
facility: Toronto Research Centre
state: Ontario
city: Toronto
country: Canada
facility: Sameh Hanna Medicine Professional Corporation DBA Dermatology on Bloor
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Windsor
country: Canada
facility: Windsor Clinical Research Inc.
state: Ontario
city: Drummondville
country: Canada
facility: Dr Isabelle Delorme inc
state: Quebec
city: Saint-Jerome
country: Canada
facility: Dre Angelique Gagne-Henley M.D. Inc.
state: Quebec
city: Saskatoon
country: Canada
facility: Skinsense Medical Research
state: Saskatchewan
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.
citation: 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.