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

Palmoplantaris Pustulosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04057937
• Other study ID #: CC-10004-PPP-001
• Secondary ID: U1111-1236-1239
• Status: Completed
• Phase: Phase 2
• Start date: October 16, 2019
• Est. completion date: June 7, 2021

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: June 7, 2021
• Est. primary completion date: January 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject has a diagnosis of Palmoplantar Pustulosis with or without pustulotic arthro-osteitis (PAO) for at least 24 weeks before screening.

2. Subject has a total score of PPPASI: = 12 at screening and baseline.

3. Subject has moderate or severe pustules/vesicles on palms or soles (PPPASI severity score: = 2) at screening and baseline.

4. 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:

1. Subject has a diagnosis of plaque-type psoriasis.

2. Subject has the presence of pustular psoriasis in any part of the body other than the palms and soles.

3. Subject has obvious improvement during screening (= 5 PPPASI total score improvement during the screening).

4. Subject has received any procedures for focal infection (e.g, tonsillectomy and dental therapy) within 24 weeks of baseline.

5. Subject has periodontitis obviously requiring treatment at screening.

6. Subject has chronic or recurrent tonsillitis or sinusitis requiring any continuous treatment for a month or more at screening.

7. Subject has evidence of skin conditions of hands and feet that would interfere with evaluations of the effect of study medication.

8. Subject is pregnant or breastfeeding.

Related Conditions & MeSH terms

• Palmoplantaris Pustulosis
• Psoriasis

Intervention

Drug:
• Apremilast
Apremilast
• Placebo
Placebo

Locations

Country	Name	City	State
Japan	Research Site	Chiyoda-ku	Tokyo
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Hitachi	Ibaraki
Japan	Research Site	Ichinomiya	Aichi
Japan	Research Site	Itabashi-ku	Tokyo
Japan	Research Site	Itabashi-ku
Japan	Research Site	Izumo	Shimane
Japan	Research Site	Kisarazu
Japan	Research Site	Kofu
Japan	Research Site	Minokamo
Japan	Research Site	Nagoya	Aichi
Japan	Research Site	Nankoku-shi
Japan	Research Site	Osaka
Japan	Research Site	Sagamihara-shi	Kanagawa
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sendai
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shinjyuku-ku
Japan	Research Site	Toon
Japan	Research Site	Tsu
Japan	Research Site	Yokohoma-shi	Kanagawa
Japan	Research Site	Yokosuka	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Terui T, Okubo Y, Kobayashi S, Sano S, Morita A, Imafuku S, Tada Y, Abe M, Yaguchi M, Uehara N, Handa T, Tanaka M, Zhang W, Paris M, Murakami M. Efficacy and Safety of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: Results from a Phase 2, Randomized, Placebo-Controlled Study. Am J Clin Dermatol. 2023 Sep;24(5):837-847. doi: 10.1007/s40257-023-00788-2. Epub 2023 May 26. Erratum In: Am J Clin Dermatol. 2024 Jan;25(1):165-167. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   AmgenTrials clinical trials website