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

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

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.

Study Overview

• Status: Completed
• Conditions: Palmoplantaris Pustulosis
• Intervention / Treatment: Drug: Placebo; Drug: Apremilast

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Itabashi-ku, Japan, 173-8610
    • Research Site
  • Kisarazu, Japan, 292-8535
    • Research Site
  • Kofu, Japan, 400-0027
    • Research Site
  • Minokamo, Japan, 505-8503
    • Research Site
  • Nankoku-shi, Japan, 783-8505
    • Research Site
  • Osaka, Japan, 550-0006
    • Research Site
  • Sendai, Japan, 980-8574
    • Research Site
  • Shinjuku-ku, Japan, 161-8521
    • Research Site
  • Shinjyuku-ku, Japan, 160-0023
    • Research Site
  • Toon, Japan, 791-0295
    • Research Site
  • Tsu, Japan, 514-8507
    • Research Site
  • Aichi
    • Ichinomiya, Aichi, Japan, 491-8558
      • Research Site
    • Nagoya, Aichi, Japan, 467-8602
      • Research Site
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 814-0180
      • Research Site
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-0063
      • Research Site
  • Ibaraki
    • Hitachi, Ibaraki, Japan, 317-0077
      • Research Site
  • Kanagawa
    • Sagamihara-shi, Kanagawa, Japan, 252-0392
      • Research Site
    • Yokohoma-shi, Kanagawa, Japan, 221-0825
      • Research Site
    • Yokosuka, Kanagawa, Japan, 238-8558
      • Research Site
  • Shimane
    • Izumo, Shimane, Japan, 693-8501
      • Research Site
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 102-8798
      • Research Site
    • Itabashi-ku, Tokyo, Japan, 173-8606
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo then Apremilast 30mg BID; 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: Placebo; Placebo; Drug: Apremilast; Apremilast; Other Names: CC-10004
Experimental: Apremilast 30 mg BID then Apremilast 30 mg BID; 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; Apremilast; Other Names: CC-10004

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Actual): January 18, 2021
• Study Completion (Actual): June 7, 2021

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; CC-10004; Apremilast; Phase 2; Palmoplantar Pustulosis; Only Japanese
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-PPP-001; U1111-1236-1239 (Other Identifier: WHO)

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; SAP; ICF; CSR

Drug and device information, study documents

• 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