A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Palmoplantaris Pustulosis

Intervention / Treatment
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* Drug: Apremilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo then Apremilast 30mg BID<br>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). | Drug: Apremilast<br>* Apremilast<br>* Other names: CC-10004;Drug: Placebo<br>* Placebo<br>|
| Experimental: Apremilast 30 mg BID then Apremilast 30 mg BID<br>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). | Drug: Apremilast<br>* Apremilast<br>* Other names: CC-10004;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Weeks 2 to 14 | 
| 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. | Weeks 2 to 16 | 
| 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. | Baseline to Week 16 | 
| 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. | Baseline to Week 16 | 
| 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. | Baseline and Week 16 | 
| 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. | Baseline to Week 16 | 
| 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. | Baseline to Week 16 | 
| 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. | Baseline and Week 16 | 
| 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. | Weeks 2 to 16 | 
| 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. | Weeks 2 to 16 | 
| 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. | Baseline and Weeks 2,4,6,8,12,16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-10004, Apremilast, Palmoplantar Pustulosis, Only Japanese, Efficacy, Safety, Phase 2