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

Primary Purpose

Dermatitis, Atopic Dermatitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Apremilast
Apremilast
Placebo
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dermatitis, Atopic Dermatitis focused on measuring Atopic Dermatitis, Atopic Eczema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Arizona Research Center
  • Bakersfield Dermatology and Skin Cancer Medical Group
  • Dermatology Research Associates
  • Renstar Medical Research
  • Emory Clinic
  • Advanced Medical Research
  • Northwestern University Northwestern Medical Faculty Foundation
  • Northwestern Medicine Lake Forest Hospital
  • Dermatology Specialists, PSC
  • Dartmouth Hitchcock Medical Center
  • NYU Department of Dermatology
  • Mount Sinai Medical Center
  • PMG Research of Winston-Salem LLC
  • Oregon Health and Science University
  • Virginia Clinical Research Inc
  • Chih-Ho Hong Medical, Inc.
  • Eastern Canada Cutaneous Research Associates Ltd
  • Ultranova Skincare
  • K. Papp Clinical Research
  • Innovaderm Research
  • Centre Dermatologique du Quebec Metropolitain
  • Kokubu Abashiri Dermatology Clinic
  • Asanuma Dermatology Clinic
  • Fukuoka University Hospital Dermatology
  • Hatamoto Dermatology Clinic
  • Tashiro Clinic
  • Kokubu Dermatology
  • University Hospital, Kyoto Prefectural University of Medicine
  • Kyoto University Hospital
  • Sapporo Skin Clinic
  • NTT Medical Center Tokyo

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Apremilast 40 mg

Apremilast 30 mg

Placebo + Apremilast 40 mg

Placebo + Apremilast 30 mg

Placebo

Arm Description

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

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

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

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

Oral Placebo tablets administered twice daily (BID) for 12 weeks during the placebo-controlled phase.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.
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.
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.
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.

Full Information

First Posted
March 13, 2014
Last Updated
April 28, 2020
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT02087943
Brief Title
Efficacy and Safety Study of Apremilast in Subjects With Moderate to Severe Atopic Dermatitis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dermatitis, Atopic Dermatitis
Keywords
Atopic Dermatitis, Atopic Eczema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apremilast 40 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Apremilast 30 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo + Apremilast 40 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo + Apremilast 30 mg
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral Placebo tablets administered twice daily (BID) for 12 weeks during the placebo-controlled phase.
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
CC-10004, Otezla
Intervention Description
Orally twice a day (BID)
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
CC-10004, Otezla
Intervention Description
Orally twice a day (BID)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Orally twice a day (BID)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Orally twice a day (BID)
Primary Outcome Measure Information:
Title
Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 12.
Description
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.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
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.
Description
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).
Time Frame
Baseline to Week 12
Title
Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI 50) at Week 12
Description
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.
Time Frame
Baseline to Week 12
Title
The Percentage Change From Baseline in the Average Weekly Pruritus Numerical Rating Scale (NRS) Score at Week 4
Description
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.
Time Frame
Baseline to Week 4
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Period
Description
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.
Time Frame
Baseline to Week 12
Title
Number of Participants With TEAEs During the Apremilast Exposure Period
Description
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.
Time Frame
Baseline to Week 24; median duration of apremilast 30 mg was 23.3 weeks and 22.4 weeks for apremilast 40 mg

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males or females, aged ≥ 18 years (≥ 20 for Japanese subjects) at the time of consent. Have a diagnosis of atopic dermatitis for ≥ 12 months. Have moderate to severe atopic dermatitis which is considered inappropriate for topical therapy or which cannot be adequately controlled by topical therapy. Meet the laboratory criteria as defined per protocol 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 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: Active tuberculosis (TB) or a history of inadequately treated tuberculosis. Positive for hepatitis B surface antigen or hepatitis C antibody Pregnant or breast feeding History of allergy to any component of the study medication. Active skin infection requiring systemic antimicrobials at Baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Research Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Bakersfield Dermatology and Skin Cancer Medical Group
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Dermatology Research Associates
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Advanced Medical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Northwestern University Northwestern Medical Faculty Foundation
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern Medicine Lake Forest Hospital
City
Lake Forest
State/Province
Illinois
ZIP/Postal Code
60045
Country
United States
Facility Name
Dermatology Specialists, PSC
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
NYU Department of Dermatology
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
PMG Research of Winston-Salem LLC
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103-3914
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201-3098
Country
United States
Facility Name
Virginia Clinical Research Inc
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Chih-Ho Hong Medical, Inc.
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3R 6A7
Country
Canada
Facility Name
Eastern Canada Cutaneous Research Associates Ltd
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1Z2
Country
Canada
Facility Name
Ultranova Skincare
City
Barrie
State/Province
Ontario
ZIP/Postal Code
L4M 6L2
Country
Canada
Facility Name
K. Papp Clinical Research
City
Waterloo
State/Province
Ontario
ZIP/Postal Code
N2J 1C4
Country
Canada
Facility Name
Innovaderm Research
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2K 4L5
Country
Canada
Facility Name
Centre Dermatologique du Quebec Metropolitain
City
Ste-Foy
State/Province
Quebec
ZIP/Postal Code
G1V 4X7
Country
Canada
Facility Name
Kokubu Abashiri Dermatology Clinic
City
Abashiri-shi, Hokkaido
ZIP/Postal Code
093-0016
Country
Japan
Facility Name
Asanuma Dermatology Clinic
City
Chitose-shi, Hokkaido
ZIP/Postal Code
066-0064
Country
Japan
Facility Name
Fukuoka University Hospital Dermatology
City
Fukuoka-shi, Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Hatamoto Dermatology Clinic
City
Fukuoka-shi, Fukuoka
ZIP/Postal Code
815-0075
Country
Japan
Facility Name
Tashiro Clinic
City
Iizuka-shi, Fukuoka
ZIP/Postal Code
820-0040
Country
Japan
Facility Name
Kokubu Dermatology
City
Kitami-shi, Hokkaido
ZIP/Postal Code
090-0832
Country
Japan
Facility Name
University Hospital, Kyoto Prefectural University of Medicine
City
Kyoto-City
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
Sapporo Skin Clinic
City
Sapporo-shi, Hokkaido
ZIP/Postal Code
060-0063
Country
Japan
Facility Name
NTT Medical Center Tokyo
City
Shinagawa-ku, Tokyo
ZIP/Postal Code
141-8625
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Citations:
PubMed Identifier
30528828
Citation
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.
Results Reference
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Efficacy and Safety Study of Apremilast in Subjects With Moderate to Severe Atopic Dermatitis

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