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

NCT01232283 | Completed Phase 3 Results

• 1 other identifier: CC-10004-PSOR-009
• Study Type: interventional
• Target: 413
• Locations: 9 countries
• Sites: 46

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.

Conditions

Plaque Psoriasis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline

  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.

  Baseline to Week 16

Secondary Outcomes (13)

• 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

• Percent Change From Baseline in the Affected Body Surface Area (BSA) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16

  Baseline and Week 16

• Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline

  Baseline and Week 16

• Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16

  Baseline and Week 16

Study Arms (2)

Apremilast

EXPERIMENTAL

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.

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

Placebo

PLACEBO COMPARATOR

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).

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

Interventions

Apremilast DRUG

Apremilast 30mg by mouth (PO) twice a day (BID) for 32 weeks

Also known as: CC-10004, Otezla

Apremilast; Placebo

Placebo DRUG

Identically matching placebo by mouth BID for first 16 weeks. Placebo participants will be switched to receive apremilast 30 mg BID at Week 16-32.

Apremilast; Placebo

Topical or Phototherapy Therapy OTHER

Topical therapies such as low-potency or weak corticosteroids or phototherapies such as light therapy are added for non-responders at Week 32, (\< PASI-50) and added to their treatment regimen. The decision to add these treatments during this phase can only be made at the Week 32 visit.

Apremilast; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (46)

Arizona Skin and Laser Therapy Inst., Ltd.

Phoenix, Arizona, 85023, United States

Location

Burke Pharmaceutical Research

Hot Springs, Arkansas, 71913, United States

Location

Bakersfield Dermatology and Skin Cancer Medical Group

Bakersfield, California, 93309, United States

Location

Dermatology Research Associates

Los Angeles, California, 90045, United States

Location

Clinical Science Institute

Santa Monica, California, 90404, United States

Location

Florida Academic Dermatology Center

Miami, Florida, 33136, United States

Location

Advanced Medical Research

Atlanta, Georgia, 30342, United States

Location

MedaPhase Inc.

Newnan, Georgia, 30263, United States

Location

Northwestern University Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

PMG Research of Winston-Salem

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27104, United States

Location

Clinical Partners, LLC

Johnston, Rhode Island, 02919, United States

Location

Radiant Research, Inc.

Anderson, South Carolina, 29560, United States

Location

Austin Dermatology Associates

Austin, Texas, 78705, United States

Location

Modern Research Associates PLLC

Dallas, Texas, 75231, United States

Location

Center for Clinical Studies

Houston, Texas, 77004, United States

Location

Center for Clinical Studies

Webster, Texas, 77598, United States

Location

Virginia Medical Research

Norfolk, Virginia, 23507, United States

Location

Medizinische Universitat Wien, Universitatsklinik fur Dermatologie. Abteilung fur Immundermatologie

Vienna, 1090, Austria

Location

Northwest Dermatology and Laser Centre

Calgary, Alberta, T3G 0B4, Canada

Location

Stratica Medical

Edmonton, Alberta, T5K 1X3, Canada

Location

NewLab Clinical Research

St. John's, Newfoundland and Labrador, A1C 2H5, Canada

Location

Skin Center for Dermatology

Peterborough, Ontario, K9J 5K2, Canada

Location

Windsor Clinical Research Inc.

Winsor, Ontario, N8W 5L7, Canada

Location

Q & T Research Sherbrooke Inc.

Sherbrooke, Quebec, J1H 4J6, Canada

Location

Centre de Recherche Dermatologique du Quebec Metropolitain CRDQ

Québec, G1V 4X7, Canada

Location

Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Centre d'lnvestigation Clinique, Hopital Jean Minjoz

Besançon, 25030, France

Location

Hospital haut leveque

Pessac, 33604, France

Location

Larrey University Hospital

Toulouse, 31000, France

Location

Dr. med. Beatrice Gerlach

Dresden, 01097, Germany

Location

Universitatsklinikum Hamburg-Eppendorf / IVDP

Hamburg, D-20246, Germany

Location

Universitäts-Hautklinik Kiel

Kiel, 24105, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Hautarztpraxis Mahlow

Mahlow, 15831, Germany

Location

Universita degli Studi di Napoli Federico II

Napoli, 80131, Italy

Location

Istituto Dermatologico San Gallicano IRCCS Dermatologia Clinica

Rome, 00144, Italy

Location

A.O.U. Integrata di Verona Universitá degli Studi di Verona Sezione di Dermatologia e Venerologia

Verona, 37126, Italy

Location

Hospital Abente y Lago

A Coruña, 15006, Spain

Location

Hospital Universitario Fundacion Alcorcon

Alcorcón, 28922, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona (Barcelona), 8916, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hopitaux Universitaires de Geneve-HUG

Geneva, 1205, Switzerland

Location

University of Zurich Hospital

Zurich, 8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 34255891 BACKGROUND

• 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.

  PMID: 37316690 DERIVED

MeSH Terms

Interventions

apremilast

Results Point of Contact

• Title: Anne McClain
• Organization: Celgene Corporation

ClinicalTrialDisclosure@celgene.com

888-260-1599

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2010
• First Posted: November 2, 2010
• Study Start: November 22, 2010
• Primary Completion: March 15, 2012
• Study Completion: November 30, 2016
• Last Updated: March 15, 2022
• Results First Posted: November 5, 2014

Record last verified: 2020-04

Locations

AU (1); CA (7); DE (5); ES (5); CH (2); US (19); IT (3); DK (1); FR (3)