Back to resultsA Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis
Primary Purpose
Palmoplantaris Pustulosis
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Apremilast
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Palmoplantaris Pustulosis focused on measuring Palmoplantar Pustulosis, CC-10004, Apremilast, Only Japanese, Efficacy, Safety, Phase 2
Eligibility Criteria
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
- Subject has a diagnosis of Palmoplantar Pustulosis with or without pustulotic arthro-osteitis (PAO) for at least 24 weeks before screening.
- Subject has a total score of PPPASI: ≥ 12 at screening and baseline.
- Subject has moderate or severe pustules/vesicles on palms or soles (PPPASI severity score: ≥ 2) at screening and baseline.
- Subject has inadequate response to treatment with topical steroid and/or topical vitamin D3 derivative preparations prior to or at screening.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
- Subject has a diagnosis of plaque-type psoriasis.
- Subject has the presence of pustular psoriasis in any part of the body other than the palms and soles.
- Subject has obvious improvement during screening (≥ 5 PPPASI total score improvement during the screening).
- Subject has received any procedures for focal infection (e.g, tonsillectomy and dental therapy) within 24 weeks of baseline.
- Subject has periodontitis obviously requiring treatment at screening.
- Subject has chronic or recurrent tonsillitis or sinusitis requiring any continuous treatment for a month or more at screening.
- Subject has evidence of skin conditions of hands and feet that would interfere with evaluations of the effect of study medication.
- Subject is pregnant or breastfeeding.
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Placebo then Apremilast 30mg BID
Apremilast 30 mg BID then Apremilast 30 mg BID
Arm Description
Participants received matched placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16). Participants who completed the placebo-controlled phase entered the active-treatment phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16). Participants who completed the placebo-controlled phase entered the active-treatment phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
Outcomes
Primary Outcome Measures
Percentage of Participants Who Achieve a PPPASI-50 at Week 16
PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease.
Secondary Outcome Measures
Percentage of Participants Who Achieve a PPPASI-50 at All Other Visits in Placebo-controlled Phase
PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values at were imputed using non-responder imputation (NRI) as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Percentage of Participants Who Achieve a PPPASI-75 at Each Visit in Placebo-controlled Phase
PPPASI-75 is defined as >=75 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Area Under the Curve (AUC) of PPPASI Total Score From Baseline Through Week 16
The AUC for PPPASI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method.
PPPASI is a disease-specific efficacy assessment tool to evaluate 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease.
Percent Change From Baseline in PPPASI Total Score by Visit in Placebo-controlled Phase .
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. A positive change from baseline indicates a worsening of symptoms.
Change From Baseline in PPPASI Total Score at Week 16
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms.
AUC for PPSI Total Score From Baseline Through Week 16
The AUC for PPSI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method. PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease.
Percent Change From Baseline in PPSI Total Score by Visit in Placebo-controlled Phase
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. A positive change from baseline indicates a worsening of symptoms.
Change From Baseline in PPSI Total Score at Week 16
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms.
Percentage of Participants Achieving a PGA Score of Clear (0) or Minimal (1) by Visit in Placebo-controlled Phase
The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:
0 = Clear
= Almost clear/Minimal
= Mild
= Moderate
= Severe
= Very severe.
The percentage of of participants with a post baseline score of 0 or 1 (responders) are reported. Missing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Percentage of Participants Achieving a PGA Score of 0 or 1 With At Least a 2 Grade Improvement by Visit in Placebo-controlled Phase.
The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:
0 = Clear
= Almost clear/Minimal
= Mild
= Moderate
= Severe
= Very severe.
The percentage of of participants with at least a 2 grade improvement from baseline (stringent responders) are reported. issing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Change From Baseline in Participant VAS Assessment for PPP Symptoms
Participants assessed the degree of both pruritus itching and skin discomfort/pain as symptoms on hands and feet caused by PPP on a VAS. Each score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no itch/pain and the right-hand boundary (100) represents itch/pain as severe as can be imagined by participant.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04057937
Brief Title
A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis
Official Title
A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Palmoplantar Pustulosis in Japan
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
October 16, 2019 (Actual)
Primary Completion Date
January 18, 2021 (Actual)
Study Completion Date
June 7, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate whether apremilast is better than placebo (inactive substance in the same form as the drug) for the treatment in Japanese subjects with PPP. This study also will evaluate the safety and tolerability of apremilast in Japanese subjects with PPP.CC-10004-PPP-001 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, Phase 2 study of apremilast in Japanese subjects with PPP and inadequate response to treatment with topical steroid and/or topical vitamin D3 derivative preparations.
The placebo-controlled period will be 16 weeks and patients will receive apremilast or placebo. After the 16-week placebo-controlled period, all subjects will receive apremilast for 16 weeks. All subjects will have their final study visit 4 weeks after stopping apremilast treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Palmoplantaris Pustulosis
Keywords
Palmoplantar Pustulosis, CC-10004, Apremilast, Only Japanese, Efficacy, Safety, Phase 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo then Apremilast 30mg BID
Arm Type
Experimental
Arm Description
Participants received matched placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16). Participants who completed the placebo-controlled phase entered the active-treatment phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
Arm Title
Apremilast 30 mg BID then Apremilast 30 mg BID
Arm Type
Experimental
Arm Description
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16). Participants who completed the placebo-controlled phase entered the active-treatment phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
CC-10004
Intervention Description
Apremilast
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieve a PPPASI-50 at Week 16
Description
PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease.
Time Frame
At Week 16
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieve a PPPASI-50 at All Other Visits in Placebo-controlled Phase
Description
PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values at were imputed using non-responder imputation (NRI) as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Time Frame
Weeks 2 to 14
Title
Percentage of Participants Who Achieve a PPPASI-75 at Each Visit in Placebo-controlled Phase
Description
PPPASI-75 is defined as >=75 percent decrease in PPPASI total score from baseline.
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Time Frame
Weeks 2 to 16
Title
Area Under the Curve (AUC) of PPPASI Total Score From Baseline Through Week 16
Description
The AUC for PPPASI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method.
PPPASI is a disease-specific efficacy assessment tool to evaluate 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease.
Time Frame
Baseline to Week 16
Title
Percent Change From Baseline in PPPASI Total Score by Visit in Placebo-controlled Phase .
Description
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. A positive change from baseline indicates a worsening of symptoms.
Time Frame
Baseline to Week 16
Title
Change From Baseline in PPPASI Total Score at Week 16
Description
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms.
Time Frame
Baseline and Week 16
Title
AUC for PPSI Total Score From Baseline Through Week 16
Description
The AUC for PPSI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method. PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease.
Time Frame
Baseline to Week 16
Title
Percent Change From Baseline in PPSI Total Score by Visit in Placebo-controlled Phase
Description
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. A positive change from baseline indicates a worsening of symptoms.
Time Frame
Baseline to Week 16
Title
Change From Baseline in PPSI Total Score at Week 16
Description
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms.
Time Frame
Baseline and Week 16
Title
Percentage of Participants Achieving a PGA Score of Clear (0) or Minimal (1) by Visit in Placebo-controlled Phase
Description
The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:
0 = Clear
= Almost clear/Minimal
= Mild
= Moderate
= Severe
= Very severe.
The percentage of of participants with a post baseline score of 0 or 1 (responders) are reported. Missing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Time Frame
Weeks 2 to 16
Title
Percentage of Participants Achieving a PGA Score of 0 or 1 With At Least a 2 Grade Improvement by Visit in Placebo-controlled Phase.
Description
The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:
0 = Clear
= Almost clear/Minimal
= Mild
= Moderate
= Severe
= Very severe.
The percentage of of participants with at least a 2 grade improvement from baseline (stringent responders) are reported. issing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder.
Time Frame
Weeks 2 to 16
Title
Change From Baseline in Participant VAS Assessment for PPP Symptoms
Description
Participants assessed the degree of both pruritus itching and skin discomfort/pain as symptoms on hands and feet caused by PPP on a VAS. Each score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no itch/pain and the right-hand boundary (100) represents itch/pain as severe as can be imagined by participant.
Time Frame
Baseline and Weeks 2,4,6,8,12,16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
Subject has a diagnosis of Palmoplantar Pustulosis with or without pustulotic arthro-osteitis (PAO) for at least 24 weeks before screening.
Subject has a total score of PPPASI: ≥ 12 at screening and baseline.
Subject has moderate or severe pustules/vesicles on palms or soles (PPPASI severity score: ≥ 2) at screening and baseline.
Subject has inadequate response to treatment with topical steroid and/or topical vitamin D3 derivative preparations prior to or at screening.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
Subject has a diagnosis of plaque-type psoriasis.
Subject has the presence of pustular psoriasis in any part of the body other than the palms and soles.
Subject has obvious improvement during screening (≥ 5 PPPASI total score improvement during the screening).
Subject has received any procedures for focal infection (e.g, tonsillectomy and dental therapy) within 24 weeks of baseline.
Subject has periodontitis obviously requiring treatment at screening.
Subject has chronic or recurrent tonsillitis or sinusitis requiring any continuous treatment for a month or more at screening.
Subject has evidence of skin conditions of hands and feet that would interfere with evaluations of the effect of study medication.
Subject is pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Ichinomiya
State/Province
Aichi
ZIP/Postal Code
491-8558
Country
Japan
Facility Name
Research Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Research Site
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
060-0063
Country
Japan
Facility Name
Research Site
City
Hitachi
State/Province
Ibaraki
ZIP/Postal Code
317-0077
Country
Japan
Facility Name
Research Site
City
Sagamihara-shi
State/Province
Kanagawa
ZIP/Postal Code
252-0392
Country
Japan
Facility Name
Research Site
City
Yokohoma-shi
State/Province
Kanagawa
ZIP/Postal Code
221-0825
Country
Japan
Facility Name
Research Site
City
Yokosuka
State/Province
Kanagawa
ZIP/Postal Code
238-8558
Country
Japan
Facility Name
Research Site
City
Izumo
State/Province
Shimane
ZIP/Postal Code
693-8501
Country
Japan
Facility Name
Research Site
City
Chiyoda-ku
State/Province
Tokyo
ZIP/Postal Code
102-8798
Country
Japan
Facility Name
Research Site
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-8606
Country
Japan
Facility Name
Research Site
City
Itabashi-ku
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Research Site
City
Kisarazu
ZIP/Postal Code
292-8535
Country
Japan
Facility Name
Research Site
City
Kofu
ZIP/Postal Code
400-0027
Country
Japan
Facility Name
Research Site
City
Minokamo
ZIP/Postal Code
505-8503
Country
Japan
Facility Name
Research Site
City
Nankoku-shi
ZIP/Postal Code
783-8505
Country
Japan
Facility Name
Research Site
City
Osaka
ZIP/Postal Code
550-0006
Country
Japan
Facility Name
Research Site
City
Sendai
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Research Site
City
Shinjuku-ku
ZIP/Postal Code
161-8521
Country
Japan
Facility Name
Research Site
City
Shinjyuku-ku
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Research Site
City
Toon
ZIP/Postal Code
791-0295
Country
Japan
Facility Name
Research Site
City
Tsu
ZIP/Postal Code
514-8507
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
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis
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