Efficacy and Safety Study of Apremilast in Subjects With Moderate to Severe Atopic Dermatitis

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Atopic Dermatitis

A study to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with moderate to severe atopic dermatitis

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic Dermatitis
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Chih-Ho Hong Medical, Inc.
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1Z2
      • Eastern Canada Cutaneous Research Associates Ltd
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Ultranova Skincare
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research
    • Ste-Foy, Quebec, Canada, G1V 4X7
      • Centre Dermatologique du Quebec Metropolitain
• Japan
  • Abashiri-shi, Hokkaido, Japan, 093-0016
    • Kokubu Abashiri Dermatology Clinic
  • Chitose-shi, Hokkaido, Japan, 066-0064
    • Asanuma Dermatology Clinic
  • Fukuoka-shi, Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital Dermatology
  • Fukuoka-shi, Fukuoka, Japan, 815-0075
    • Hatamoto Dermatology Clinic
  • Iizuka-shi, Fukuoka, Japan, 820-0040
    • Tashiro Clinic
  • Kitami-shi, Hokkaido, Japan, 090-0832
    • Kokubu Dermatology
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto-City, Japan, 602-8566
    • University Hospital, Kyoto Prefectural University of Medicine
  • Sapporo-shi, Hokkaido, Japan, 060-0063
    • Sapporo Skin Clinic
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • NTT Medical Center Tokyo
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Bakersfield, California, United States, 93309
      • Bakersfield Dermatology and Skin Cancer Medical Group
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
  • Florida
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
    • Atlanta, Georgia, United States, 30342
      • Advanced Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Northwestern Medical Faculty Foundation
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Dermatology Specialists, PSC
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • NYU Department of Dermatology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103-3914
      • PMG Research of Winston-Salem LLC
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Oregon Health and Science University
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Virginia Clinical Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, aged ≥ 18 years (≥ 20 for Japanese subjects) at the time of consent.
2. Have a diagnosis of atopic dermatitis for ≥ 12 months.
3. Have moderate to severe atopic dermatitis which is considered inappropriate for topical therapy or which cannot be adequately controlled by topical therapy.
4. Meet the laboratory criteria as defined per protocol
5. Females of Childbearing Potential (FCBP) must have a negative pregnancy test at Screening and Baseline. Sexually active FCBP must use one of the approved contraceptive options required per protocol while on and for at least 28 days after the last dose of study medication
6. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception while on and for at least 28 days after the last dose of study medication.

Exclusion Criteria:

1. Active tuberculosis (TB) or a history of inadequately treated tuberculosis.
2. Positive for hepatitis B surface antigen or hepatitis C antibody
3. Pregnant or breast feeding
4. History of allergy to any component of the study medication.
5. Active skin infection requiring systemic antimicrobials at Baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast 40 mg; Apremilast 40 mg administered orally twice daily (BID) for 12 weeks (following dose titration) during the placebo controlled phase followed by 40 mg Apremilast tablets orally administered BID for an additional 12 weeks in the active treatment phase	Drug: Apremilast; Orally twice a day (BID); Other Names: CC-10004; Otezla
Experimental: Apremilast 30 mg; Apremilast 30 mg administered orally BID for 12 weeks (following dose titration) during the placebo controlled phase followed by 30 mg Apremilast tablets orally administered BID for an additional 12 weeks in the active treatment phase	Drug: Apremilast; Orally twice a day (BID); Other Names: CC-10004; Otezla
Experimental: Placebo + Apremilast 40 mg; Placebo administered orally BID for 12 weeks, during the placebo controlled phase followed by 40 mg Apremilast tablets orally BID for an additional 12 weeks in the active treatment phase	Drug: Apremilast; Orally twice a day (BID); Other Names: CC-10004; Otezla; Drug: Placebo; Orally twice a day (BID)
Experimental: Placebo + Apremilast 30 mg; Placebo administered orally BID for 12 weeks, during the placebo controlled phase followed by 30 mg Apremilast tablets orally BID for an additional 12 weeks in the active treatment phase	Drug: Apremilast; Orally twice a day (BID); Other Names: CC-10004; Otezla; Drug: Placebo; Orally twice a day (BID)
Placebo Comparator: Placebo; Oral Placebo tablets administered twice daily (BID) for 12 weeks during the placebo-controlled phase.	Drug: Placebo; Orally twice a day (BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 12.	EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). A representative lesion is selected for each of the four body regions for assessing the intensity of each of the four signs (erythema, induration /papulation, excoriation, and lichenification). Symptoms (eg, pruritus) and secondary signs (eg, xerosis, scaling) are excluded from the assessment. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Score of 0 (Cleared) or 1 (Almost Cleared) and at Least a 2-point Reduction From Baseline in a Static Physician's Global Assessment of Acute Signs (sPGA-A) at Week 12.	The sPGA-A is intended to assess the global severities (ie, a "visual average" integrating all areas of AD) of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded) based on a 5-point scale of cleared (0), almost cleared (1), mild (2), moderate (3) and severe (4).	Baseline to Week 12
Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI 50) at Week 12	The EASI 50 reduction (defined as ≥ 50% reduction from baseline in EASI score) was selected to serve as the key responder endpoint. A ≥ 50% improvement is clinically meaningful for this population.	Baseline to Week 12
The Percentage Change From Baseline in the Average Weekly Pruritus Numerical Rating Scale (NRS) Score at Week 4	The participant completed a daily diary recording the average intensity of pruritus they experienced during the preceding 24 hrs. The intensity of pruritus was assessed using a validated 11-point NRS, ranging from 0 ("no pruritus") to 10 ("the worst pruritus imaginable"). It should be noted that this NRS is distinct from the pruritus, Visual Analogue Scale (VAS) in the Modified SCORAD Index with respect to recall period (three days for the VAS). The weekly NRS score was calculated as the average of the NRS scores over 7 days within the specified week. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.	Baseline to Week 4
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Period	A TEAE is an adverse event with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.	Baseline to Week 12
Number of Participants With TEAEs During the Apremilast Exposure Period	A TEAE is an adverse event with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event.	Baseline to Week 24; median duration of apremilast 30 mg was 23.3 weeks and 22.4 weeks for apremilast 40 mg

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Simpson EL, Imafuku S, Poulin Y, Ungar B, Zhou L, Malik K, Wen HC, Xu H, Estrada YD, Peng X, Chen M, Shah N, Suarez-Farinas M, Pavel AB, Nograles K, Guttman-Yassky E. A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis. J Invest Dermatol. 2019 May;139(5):1063-1072. doi: 10.1016/j.jid.2018.10.043. Epub 2018 Dec 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: March 13, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Atopic Dermatitis; Atopic Eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Thalidomide; Apremilast
• Other Study ID Numbers: CC-10004-AD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)