Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis - Full Text View

Purpose

This study will test the clinical effectiveness and safety of apremilast, etanercept compared with placebo in the same group of patients with moderate to severe plaque psoriasis.

Apremilast (CC-10004) is a new oral agent that is under clinical development for the treatment of inflammatory autoimmune disorders, such as psoriatic arthritis, psoriasis, rheumatoid arthritis, and Behçet disease.

Etanercept is approved for the treatment of psoriasis; it is the most widely prescribed anti-tumor necrosis factor (TNF) for psoriasis.

Condition	Intervention	Phase
Psoriasis Psoriatic Arthritis	Drug: Apremilast 30 mg Drug: Etanercept 50 mg Drug: Placebo tablet Drug: Placebo injection (saline)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3b, Multicenter, Randomized, Placebo-Controlled, Double Blind, Double-Dummy, Study of the Efficacy and Safety of Apremilast (CC-10004), Etanercept, and Placebo, in Subjects With Moderate to Severe Plaque Psoriasis

Resource links provided by NLM:

Genetics Home Reference related topics: psoriatic arthritis

MedlinePlus related topics: Psoriasis

Drug Information available for: Etanercept

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Apremilast Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects with either apremilast 30 mg twice a day (BID) or placebo who achieve at least a 75% reduction in PASI (PASI-75) at Week 16 from baseline

Secondary Outcome Measures:

Etanercept Psoriasis Area and Severity Index-75 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects treated with either etanercept 50mg once weekly (QW) or placebo who achieve PASI-75 (at least a 75% reduction in PASI from baseline
Disease Severity Score [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects with a Static Physician's Global Assessment (sPGA) of overall disease severity score of clear (0) or almost clear (1) with at least 2 points reduction from baseline
Percent change from baseline in the body surface area (BSA) affected by psoriasis [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Percent change from baseline in the body surface area (BSA) affected by psoriasis
Psoriasis Area and Severity Index-50 (PASI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects who achieve PASI-50 (at least a 50% reduction in PASI from baseline)
Dermatology Life Quality Index (DLQI) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Change from baseline in the Dermatology Life Quality Index (DLQI) total score
Mental Component Summary (MCS) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Change from baseline in the Mental Component Summary (MCS) score of the Medical Outcome Study Short Form 36 - item Health Survey (SF-36)
Lattice System Physician's Global Assessment (LS-PGA) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Proportion of subjects with a Lattice System Physician's Global Assessment (LS-PGA) of psoriasis severity score of clear (0) or almost clear (1)
Adverse Event [ Time Frame: Week 16 and week 104 ] [ Designated as safety issue: Yes ]
Number of participants with adverse events

Estimated Enrollment:	240
Study Start Date:	September 2012
Estimated Study Completion Date:	August 2015
Estimated Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Apremilast 30 mg plus placebo injection	Drug: Apremilast 30 mg Apremilast 30 mg tablet orally twice a day Other Name: CC-10004 Drug: Placebo injection (saline) once weekly evaluator/subject-blinded subcutaneous saline (placebo) injections (1 mL x 2 injections SC) Other Name: Placebo
Experimental: Etanercept 50 mg plus placebo tablet	Drug: Etanercept 50 mg Etanercept 50 mg evaluator/subject-blinded subcutaneous once weekly injection Other Name: ETN Drug: Placebo tablet Placebo tablets twice a day Other Name: Placebo
Placebo Comparator: Placebo	Drug: Placebo tablet Placebo tablets twice a day Other Name: Placebo Drug: Placebo injection (saline) once weekly evaluator/subject-blinded subcutaneous saline (placebo) injections (1 mL x 2 injections SC) Other Name: Placebo

Detailed Description:

This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind, double-dummy, study of the efficacy and safety of apremilast, etanercept, and placebo, in subjects with moderate to severe plaque psoriasis.

Approximately 240 subjects will be randomized 1:1:1 to the three treatment groups. All subjects will receive both tablets and injections through Week 16.

The study will consist of four phases:

Screening Phase - up to 35 days
Double-blind Placebo-controlled Phase - Weeks 0-16
Apremilast Extension Phase - Weeks 16-104
Post-treatment Observational Follow-up Phase

During the double-blind, placebo-controlled phase, subjects will receive treatment with one of the following:

apremilast (APR) 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections (1 mL x 2 injections SC), or
etanercept (ETN) 50 mg evaluator/subject-blinded subcutaneous (SC) once weekly (QW) injections (2 x 25 mg) plus placebo tablets orally twice a day (BID), or
placebo tablets and evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections.

All subjects will be asked to participate in a 4-week Post-treatment Observational Follow-up Phase either upon completion of the study or upon discontinuation of investigational product for those subjects who terminate the study early.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males or females, ≥ 18 years of age
Diagnosis of chronic, moderate to severe plaque psoriasis for at least 12 months prior to Screening, and a candidate for phototherapy and/or systemic (including etanercept) therapy
Had an inadequate response, intolerance, or contraindication to at least 1 conventional systemic agent for the treatment of psoriasis.
No prior exposure to biologics for treatment of psoriatic arthritis or psoriasis

Exclusion Criteria:

Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; 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.
Pregnant or breast feeding.
Have failed more than 3 systemic agents for treatment of psoriasis.
History of allergy to any component of the investigational product (IP), including human immunoglobulin (Ig) proteins or allergy to etanercept.
Hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.
Latent, active tuberculosis (TB) or inadequately treated TB; nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, Clostridium difficile).
Have a history of, or ongoing, chronic or recurrent infectious disease
Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months before first administration of IP, or through Week 20 during the study.
Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.
History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
Active substance abuse or a history of substance abuse within 6 months prior to Screening.
Malignancy or history of malignancy, except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and 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.
Topical therapy within 2 weeks of randomization or systemic therapy for psoriasis within 4 weeks prior to randomization
Use of phototherapy within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
Any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer).
Prior treatment with apremilast or etanercept.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690299

Contacts

Contact: Dale McElveen, MBA	732 652 6699	dmcelveen@celgene.com
Contact: Markus Kocher, PhD	+41 32 729 8794	mkocher@celgene.com

Show 38 Study Locations

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Lilia Pineda, MD

Celgene Corporation

More Information

No publications provided

Responsible Party:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT01690299 History of Changes
Other Study ID Numbers:	CC-10004-PSOR-010, 2012-000859-14
Study First Received:	September 19, 2012
Last Updated:	April 12, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Germany: Federal Institute for Drugs and Medical Devices Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:

Psoriasis
arthritis
psoriatic

psoriasis
palmoplantar
scalp

Additional relevant MeSH terms:

Arthritis
Arthritis, Psoriatic
Psoriasis
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Skin Diseases, Papulosquamous
Skin Diseases
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 21, 2013