Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

NCT ID: NCT00773734

Last Updated: 2020-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-01
• Study Completion Date: 2015-05-20

Brief Summary

The purpose of this study was to test if the drug apremilast was safe, if it helped improve psoriasis, and how well the participants tolerated it.

Detailed Description

This study fully explored the extent of treatment benefit achieved with doses of apremilast up to 30 mg by mouth (PO) twice daily (BID) with treatment duration for up to 6 months. In addition, it was important to determine the minimally effective dose for apremilast and more fully elucidate the dose response curve in this patient population. The results from this study helped guide the selection of the dose in the phase 3 trials.

Participants meeting eligibility criteria at the Baseline Visit (Week 0) were centrally randomized with the use of a permuted-block randomization list, with equal allocation to each of the four treatment arms: 10 mg, 20 mg or 30 mg PO BID of apremilast or placebo. In an effort to mitigate the dose-dependent adverse effects of apremilast (e.g., headache or gastrointestinal disturbances), participants had their dose titrated over a 7-day period (Days 1 through7). Participants received 10 mg PO BID of apremilast or identically-appearing placebo during Days 1 to 2. Participants randomized to the 10 mg BID dose continued taking this dose throughout the treatment phase of the study. Those participants randomized to the 20 mg BID dose were dose titrated to 20 mg PO BID of apremilast or identically-appearing placebo during Days 3 to 4 of dosing. Participants randomized to the 20 mg BID dose continued taking this dose throughout the treatment phase of the study. Those participants randomized to the 30 mg BID dose were dose titrated to 30 mg PO BID of apremilast or identically-appearing placebo during Days 5 to 7 and continued taking this dose throughout the treatment phase of the study. At Week 16, all participants originally randomized to the placebo arm were re-randomized to 20 mg BID or 30 mg BID of apremilast. All participants (i.e., those that were continuing their Apremilast dosing regimen, as well as those that were switched from placebo to apremilast) received drug at Week 16 in a treatment arm in a blinded fashion. In addition, participants who transitioned from placebo to active medication at Week 16 completed a dose titration schedule to help mitigate any potential GI side effects that may have jeopardized the blinding of the treatment arms.

At Week 24 (end of core study and beginning of an extension study), participants were given the option to enroll into an extension study (PSOR-005E NCT00953875) and continue on the same apremilast dosage they had received at the end of the core study, during Weeks 24-52, a total of 28 weeks. Participants who elected not to enter into the treatment extension study, completed a 4-week observational follow-up phase of the core study. At Week 52 (end of extension study and beginning of a long-term extension study), participants were given the option to enroll into a long term extension study (PSOR-005LTE NCT01130116), for 4 additional years. Participants who were treated with apremilast 10 mg BID in the extension study were randomly assigned and dose titrated to either apremilast 20 mg BID or 30 mg BID. Participants who were dosed with 20mg or 30 mg BID in the extension study continued to receive the same dose in the long-term extension study. The long-term extension study is anticipated to complete in May 2016.

Conditions

Psoriasis; Plaque-type Psoriasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Apremilast 10mg

Apremilast 10 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 10 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase

Group Type: EXPERIMENTAL

Apremilast 10mg

Intervention Type: DRUG

Apremilast 20mg

Apremilast 20 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 20 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase

Group Type: EXPERIMENTAL

Apremilast 20mg

Intervention Type: DRUG

Apremilast 30 mg

Apremilast 30 mg administered orally twice daily (BID) for 16 weeks (following dose titration) during the placebo controlled phase followed by 30 mg Apremilast tablets orally administered BID for 8 weeks in the active treatment phase

Group Type: EXPERIMENTAL

Apremilast 30 mg

Intervention Type: DRUG

Placebo

Oral Placebo tablets administered twice daily (BID) for 16 weeks during the placebo-controlled phase.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo/Apremilast 20 mg

Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase are re-randomized to 20 mg apremilast BID during the 8 week active treatment phase

Group Type: EXPERIMENTAL

Apremilast 20mg

Intervention Type: DRUG

Placebo/Apremilast 30mg

Participants initially randomized to receive placebo twice daily during the 16 week placebo controlled phase are re-randomized to 30 mg apremilast BID during the 8 week active treatment phase

Group Type: EXPERIMENTAL

Apremilast 30mg

Intervention Type: DRUG

Interventions

Apremilast 10mg

Intervention Type: DRUG

Apremilast 20mg

Intervention Type: DRUG

Apremilast 30 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Apremilast 30mg

Intervention Type: DRUG

Apremilast 20mg

Intervention Type: DRUG

Other Intervention Names

Apremilast tablets; CC-10004; Otezla; Apremilast tablets; CC-10004; Otezla; Apremilast tablets; CC-10004; Otezla; Apremilast tablets; CC-10004; Otezla; Apremilast tablets; CC-10004; Otezla

Eligibility Criteria

Inclusion Criteria

• Understand and voluntarily sign an informed consent form
• ≥18 years of age at the time of signing the informed consent form
• Able to adhere to the study visit schedule and other protocol requirements.
• Diagnosis of chronic, stable plaque psoriasis at least 6 months prior to screening as defined by:

1. PASI (Psoriasis Area and Severity Index) score ≥ 12

2. Body Surface Area (BSA) ≥ 10%

• Candidate for photo/systemic therapy
• In good health as judged by the investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology, immunology, and urinalysis
• Meet all laboratory criteria as defined per protocol
• Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the following adequate forms of contraception methods. A FCBP must agree to have pregnancy tests every 4 weeks while on study medication
• Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for 84 days after taking the last dose of study medication

Exclusion Criteria

• History of clinically significant disease (as determined by the investigator)
• Pregnant or breastfeeding
• History of active mycobacterial infection within 3 years
• History of Human Immunodeficiency Virus (HIV) infection
• Congenital and acquired immunodeficiencies
• Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
• Antibodies to Hepatitis C at screening
• Malignancy or history of malignancy except for treated [i.e., cured] basal-cell skin carcinomas
• Any condition, including the presence of laboratory abnormalities, that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Psoriasis flare within 4 weeks of screening
• Topical therapy within 2 weeks of randomization
• Systemic therapy for psoriasis within 4 weeks of randomization
• Use of phototherapy within 4 weeks of randomization [(i.e., Ultraviolet (UVB), Psoralens and long-wave ultraviolet radiation (PUVA)]
• Adalimumab, etanercept, efalizumab or infliximab within 12 weeks of randomization
• Alefacept within 24 weeks of randomization
• Investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)
• Prolonged sun exposure or use of tanning booths or other ultraviolet light sources

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Associates In Research Inc

Fresno, California, United States

Dermatology Associates

Los Angeles, California, United States

Stanford University School of Medicine

Redwood City, California, United States

Atlantic Skin & Cosmetic Surgery Group, PC

Wilmington, Delaware, United States

Renstar Medical Research

Ocala, Florida, United States

Atlanta Dermatology, Vein & Research Center

Alpharetta, Georgia, United States

NorthShore University HealthSystem

Skokie, Illinois, United States

Dawes/Fretzin Dermatology Group Inc

Indianapolis, Indiana, United States

Dermatology & Advanced Aesthetics

Lake Charles, Louisiana, United States

Minnesota Clinical Study Center

Fridley, Minnesota, United States

Central Dermatology

St Louis, Missouri, United States

UMDNJ Robert Wood Johnson

New Brunswick, New Jersey, United States

Wright State University

Dayton, Ohio, United States

Allergy, Asthma and Dermatology Research Center

Lake Oswego, Oregon, United States

Northwest Cutaneous Research Specialists

Portland, Oregon, United States

Oregon Med. Research Center, PC

Portland, Oregon, United States

Rivergate Dermatology Clinical Research

Goodlettsville, Tennessee, United States

Modern Research Associates

Dallas, Texas, United States

Dermatology Associates of Seattle

Seattle, Washington, United States

Aurora Advanced Healthcare, Inc

Milwaukee, Wisconsin, United States

Stratica Medical

Edmonton, Alberta, Canada

Dr. Lorne E. Albrecht

Surrey, British Columbia, Canada

Alpha Clinical Research Centre

St. John's, Newfoundland and Labrador, Canada

Eastern Canada Cutaneous Research Associates

Halifax, Nova Scotia, Canada

Ultranova Skincare

Barrie, Ontario, Canada

Dermatrials Research Division

Hamilton, Ontario, Canada

Guenther Dermatology Research Centre

London, Ontario, Canada

North Bay Dermatology Centre

North Bay, Ontario, Canada

Dr. Michael Robern

Ottawa, Ontario, Canada

K. Papp Clinical Research Inc.

Waterloo, Ontario, Canada

XLR8 Research

Windsor, Ontario, Canada

Innovaderm Research Laval Inc.

Laval, Quebec, Canada

Centre De Recherche Dermatologique du Qu

MetSte-Foy, Quebec, Canada

Innovaderm Research Inc.

Montreal, Quebec, Canada

International Dermatology Research, Inc.

Montreal, Quebec, Canada

Countries

United States; Canada

References

Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, Hu C, Day RM. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet. 2012 Aug 25;380(9843):738-46. doi: 10.1016/S0140-6736(12)60642-4. Epub 2012 Jun 29.

Reference Type: BACKGROUND

PMID: 22748702 (View on PubMed)

Ohtsuki M, Kubo H, Morishima H, Goto R, Zheng R, Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol. 2018 Sep;45(9):1053-1062. doi: 10.1111/1346-8138.14504. Epub 2018 Jun 15.

Reference Type: BACKGROUND

PMID: 29905383 (View on PubMed)

Knuckles MLF, Levi E, Soung J. Defining and treating moderate plaque psoriasis: a dermatologist survey. J Dermatolog Treat. 2018 Nov;29(7):658-663. doi: 10.1080/09546634.2018.1443200. Epub 2018 Mar 22.

Reference Type: BACKGROUND

PMID: 29502473 (View on PubMed)

Knuckles MLF, Levi E, Soung J. Treating moderate plaque psoriasis: prospective 6-month chart review of patients treated with apremilast. J Dermatolog Treat. 2019 Aug;30(5):430-434. doi: 10.1080/09546634.2018.1528326. Epub 2018 Nov 26.

Reference Type: BACKGROUND

PMID: 30339049 (View on PubMed)

Wu JJ, Pelletier C, Ung B, Tian M. Real-world treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriasis. J Med Econ. 2019 Apr;22(4):365-371. doi: 10.1080/13696998.2019.1571500. Epub 2019 Feb 4.

Reference Type: BACKGROUND

PMID: 30652520 (View on PubMed)

Wang Y, Coyne K, Sofen H, Santanello N, Currie B, Zhang Z, Nograles K. Qualitative analysis and reproducibility assessment of the Scalp Itch Numeric Rating Scale among patients with moderate to severe plaque psoriasis of the scalp. J Dermatolog Treat. 2019 Dec;30(8):775-783. doi: 10.1080/09546634.2019.1577546. Epub 2019 Mar 5.

Reference Type: BACKGROUND

PMID: 30747550 (View on PubMed)

Strand V, Fiorentino D, Hu C, Day RM, Stevens RM, Papp KA. Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study. Health Qual Life Outcomes. 2013 May 10;11:82. doi: 10.1186/1477-7525-11-82.

Reference Type: RESULT

PMID: 23663752 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37316690 (View on PubMed)

Other Identifiers

CC-10004-PSOR-005

Identifier Type: -

Identifier Source: org_study_id

NCT00953875

Identifier Type: -

Identifier Source: nct_alias

NCT01130116

Identifier Type: -

Identifier Source: nct_alias