NCT05174065

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

Completed Phase 3 Results posted Last updated 9 April 2025

What this trial tests

Phase 3 trial testing Apremilast in Palmoplantar Pustulosis in 176 participants. Completed in 1 June 2024.

Timeline

8 March 2022

Primary endpoint
19 August 2023

1 June 2024

Quick facts

Lead sponsor	Amgen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	176
Start date	8 March 2022
Primary completion	19 August 2023
Estimated completion	1 June 2024
Sites	40 locations across Japan

Drugs / interventions tested

• Apremilast (APREMILAST) — full drug profile →
• Placebo

Conditions studied

• Palmoplantar Pustulosis — all drugs for Palmoplantar Pustulosis →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 99, any sex, with Palmoplantar Pustulosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in Palmoplantar Pustulosis Area and Severity Index (PPPASI) Total Score (PPPASI-50) at Week 16 Primary · Baseline and Week 16

A PPPASI 50 response is defined as a ≥ 50% reduction in PPPASI total score from baseline. The PPPASI is a system used for assessing and grading the severity (in terms of erythema, pustules/vesicle and desquamation/scale) and area of PPP lesions and their response to therapy. The PPPASI produces a numeric score that can range from 0 to 72, with a higher score indicating more severe disease. Participants who discontinued investigational product before week 16 due to lack of efficacy, adverse event, or use of protocol-prohibited medication (intercurrent events) were to be considered as treatmen

Group	Value	95% CI
Placebo-controlled Period: Placebo	35.3	25.3 – 45.4
Placebo-controlled Period: Apremilast	67.8	57.9 – 77.6

Change From Baseline in PPPASI Total Score at Week 16 Secondary · Baseline and Week 16

The PPPASI is a system used for assessing and grading the severity (in terms of erythema, pustules/vesicle and desquamation/scale) and area of PPP lesions and their response to therapy. The PPPASI produces a numeric score that can range from 0 to 72, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of intercurrent event (IE) (investigational product discontinuation due to lack of efficacy, adverse event, or pr

Group	Value	95% CI
Placebo-controlled Period: Placebo	-5.98	± 0.999
Placebo-controlled Period: Apremilast	-12.12	± 1.002

Change From Baseline in Palmoplantar Pustulosis Severity Index (PPSI) Total Score at Week 16 Secondary · Baseline and Week 16

The PPSI is a system used for assessing and grading the severity of PPP lesions and their response to therapy. Evaluation of skin lesion site are assessed separately for erythema, pustules/vesicle and desquamation/scale, where each are rated on a scale of 0 to 4 and summed to produce a numeric total score than can range from 0 to 12, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational produ

Group	Value	95% CI
Placebo-controlled Period: Placebo	-1.9	± 0.24
Placebo-controlled Period: Apremilast	-3.4	± 0.24

Change From Baseline in Visual Analogue Scale (VAS) Assessment for PPP Symptoms (Pruritus) at Week 16 Secondary · Baseline and Week 16

Participants assessed the degree of pruritus itching symptoms on palms and soles caused by PPP on a VAS. The VAS score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no itch and the right-hand boundary (100) represents itch as severe as can be imagined by the participant. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medicatio

Group	Value	95% CI
Placebo-controlled Period: Placebo	-9.9	± 2.68
Placebo-controlled Period: Apremilast	-17.6	± 2.67

Change From Baseline in VAS Assessment for PPP Symptoms (Pain/Discomfort) at Week 16 Secondary · Baseline and Week 16

Participants assessed the degree of pain/discomfort symptoms on palms and soles caused by PPP on a VAS. The VAS score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no pain/discomfort and the right-hand boundary (100) represents pain/discomfort as severe as can be imagined by the participant. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol

Group	Value	95% CI
Placebo-controlled Period: Placebo	-7.5	± 2.97
Placebo-controlled Period: Apremilast	-18.3	± 2.96

Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16 Secondary · Baseline and Week 16

The DLQI is a skin disease-specific Quality of Life (QoL) questionnaire comprised of 10 items assessing the participant's status over the previous week. The DLQI was used to assess 6 different aspects that may affect QoL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI produces a numeric score ranging from 0 to 30, with a higher score indicating more severe disease. A negative change from baseline indicates a reduction in disease severity. The continuous endpoints collected on and after the participant experienced t

Group	Value	95% CI
Placebo-controlled Period: Placebo	-0.8	± 0.37
Placebo-controlled Period: Apremilast	-2.3	± 0.37

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) Secondary · Placebo-controlled period: Day 1 to Week 16; Apremilast exposure period : Apremilast Day 1 to a maximum of Week 52 (plus 4 weeks safety follow-up)

TEAEs were defined as any untoward medical occurrence in a participant irrespective of a causal relationship with the study treatment that began or worsened on or after the first dose of study treatment. A serious TEAE met at least 1 of the following criteria: * Resulted in death. * Was immediately life-threatening. * Required in-patient hospitalization or prolongation of existing hospitalization. * Resulted in persistent or significant disability/incapacity. * Was a congenital anomaly/birth defect. * Was any other medically important serious event. TEAEs of interest were defined as any of

Any TEAEs

Group	Value	95% CI
Placebo-controlled Period: Placebo	43
Placebo-controlled Period: Apremilast	63
Apremilast Exposure Period: Apremilast	148

Serious TEAEs

Group	Value	95% CI
Placebo-controlled Period: Placebo	1
Placebo-controlled Period: Apremilast	1
Apremilast Exposure Period: Apremilast	9

TEAEs of Interest

Group	Value	95% CI
Placebo-controlled Period: Placebo	3
Placebo-controlled Period: Apremilast	1
Apremilast Exposure Period: Apremilast	8

Adverse events — posted to ClinicalTrials.gov

Time frame: Placebo-controlled period: Day 1 to Week 16; Apremilast exposure period : Apremilast Day 1 to a maximum of Week 52 (plus 4 weeks safety follow-up). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo-controlled Period: Placebo

Serious: 1/88 (1%)

Deaths: 0/88

Placebo-controlled Period: Apremilast

Serious: 1/88 (1%)

Deaths: 0/88

Apremilast Exposure Period: Apremilast

Serious: 9/174 (5%)

Deaths: 0/174

Serious adverse events (11 terms)

Reaction	System	Placebo-controlled Period:…	Placebo-controlled Period:…	Apremilast Exposure Period…
Cataract	Eye disorders	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Duodenal perforation	Gastrointestinal disorders	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—
Pseudoaneurysm infection	Infections and infestations	—	—	—
Pyelonephritis	Infections and infestations	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—
Viral infection	Infections and infestations	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Cerebellar haemorrhage	Nervous system disorders	—	—	—
Cerebral infarction	Nervous system disorders	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Placebo-controlled Period:…	Placebo-controlled Period:…	Apremilast Exposure Period…
Diarrhoea	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Faeces soft	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Palmoplantar pustulosis	Skin and subcutaneous tissue disorders	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—

Most-reported serious reactions: Cataract, Acute myocardial infarction, Duodenal perforation, Cholelithiasis, Pseudoaneurysm infection, Pyelonephritis, Pyelonephritis acute, Viral infection.

Data from ClinicalTrials.gov NCT05174065 adverse events section.

Sponsor's own description

The primary objective of the study is to evaluate the efficacy of apremilast (AMG 407) twice daily (BID) compared with placebo in participants with Palmoplantar Pustulosis (PPP).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022.
   Crocetti L, Floresta G, Cilibrizzi A, Giovannoni MP. · · 2022 · cited 85× · PMID 35956914 · DOI 10.3390/molecules27154964
2. Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology.
   Carmona-Rocha E, Rusiñol L, Puig L. · · 2025 · cited 11× · PMID 39861739 · DOI 10.3390/pharmaceutics17010091
3. Apremilast in Japanese patients with palmoplantar pustulosis: A randomized, Phase 3 trial.
   Terui T, Okubo Y, Kobayashi S, Morita A, et al · · 2026 · cited 2× · PMID 41297955 · DOI 10.1111/jdv.70166
4. Summary of Research: Apremilast in Japanese Patients with Palmoplantar Pustulosis: A Randomized, Phase 3 Trial.
   Terui T, Okubo Y, Kobayashi S, Morita A, et al · · 2026 · PMID 41387650 · DOI 10.1007/s13555-025-01583-z