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

Phase 3
Completed
Conditions
Palmoplantar Pustulosis
Interventions
Drug: Placebo
Registration Number
NCT05174065
Lead Sponsor
Amgen
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
176
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo and ApremilastPlaceboMatching placebo will be administered to participants twice daily (BID) until week 16. After week 16, Apremilast will be administered to participants BID.
ApremilastApremilastApremilast will be administered to participants twice daily (BID)
Placebo and ApremilastApremilastMatching placebo will be administered to participants twice daily (BID) until week 16. After week 16, Apremilast will be administered to participants BID.
Primary Outcome Measures
NameTimeMethod
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 16Baseline 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 treatment failures as the result of the intercurrent event and the PPPASI-50 values for visits on and after the intercurrent event were imputed as non-responders. The missing PPPASI-50 values due to the other reasons were imputed using the multiple imputation method.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in PPPASI Total Score at Week 16Baseline 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 protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the mixed-effects model for repeated measures (MMRM) application.

Change From Baseline in Palmoplantar Pustulosis Severity Index (PPSI) Total Score at Week 16Baseline 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 product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Change From Baseline in VAS Assessment for PPP Symptoms (Pain/Discomfort) at Week 16Baseline 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-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Change From Baseline in Visual Analogue Scale (VAS) Assessment for PPP Symptoms (Pruritus) at Week 16Baseline 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 medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)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 the following:

* Depression.

* Serious infection.

* Risk of triggering suicide.

* Serious diarrhea, nausea and vomiting.

* Malignancies.

* Vasculitis and Vasculopathy.

* Serious Hypersensitivity.

* Weight change (weight decrease).

Clinically significant changes in body weight, vital signs and laboratory abnormalities were also recorded as TEAEs.

Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16Baseline 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 treatment failure as the result of IE (investigational product discontinuation due to lack of efficacy, adverse event, or protocol-prohibited medication use), the baseline value of corresponding endpoint were assigned to the data on and after IE up to Week 16 regardless of the observed data. The missing data due to other reasons will not be imputed considering the MMRM application.

Trial Locations

Locations (40)

Nihon University Itabashi Hospital

🇯🇵

Itabashi-ku, Tokyo, Japan

Seibo International Catholic Hospital

🇯🇵

Shinjuku-ku, Tokyo, Japan

Medical corporation kojinkai Chitose dermatology and plastic surgery clinic

🇯🇵

Chitose-shi, Hokkaido, Japan

Medical Corporation Kojinkai Sapporo Skin Clinic

🇯🇵

Sapporo-shi, Hokkaido, Japan

Aichi Medical University Hospital

🇯🇵

Nagakute-shi, Aichi, Japan

Toho University Sakura Medical Center

🇯🇵

Sakura-shi, Chiba, Japan

Ehime University Hospital

🇯🇵

Toon-shi, Ehime, Japan

Nagoya City University Hospital

🇯🇵

Nagoya-shi, Aichi, Japan

Kusuhara Dermatology Clinic

🇯🇵

Fukuoka-shi, Fukuoka, Japan

Kurume University Hospital

🇯🇵

Kurume-shi, Fukuoka, Japan

Higuchi Dermatology Urology Clinic

🇯🇵

Kasuga-shi, Fukuoka, Japan

Fukuoka University Hospital

🇯🇵

Fukuoka-shi, Fukuoka, Japan

Nagata Dermatology Clinic

🇯🇵

Ogori-shi, Fukuoka, Japan

Fukushima Medical University Hospital

🇯🇵

Fukushima-shi, Fukushima, Japan

Motomachi Dermatology Clinic

🇯🇵

Asahikawa-shi, Hokkaido, Japan

Central Japan International Medical Center

🇯🇵

Minokamo-shi, Gifu, Japan

Asahikawa Medical University Hospital

🇯🇵

Asahikawa-shi, Hokkaido, Japan

Shinoro Dermatology Clinic

🇯🇵

Sapporo-shi, Hokkaido, Japan

Medical Corporation Kojinkai Kitago Dermatology Clinic

🇯🇵

Sapporo-shi, Hokkaido, Japan

Shibaki Dermatology Clinic

🇯🇵

Sapporo-shi, Hokkaido, Japan

Mito Kyodo General Hospital

🇯🇵

Mito-shi, Ibaraki, Japan

Kobe University Hospital

🇯🇵

Kobe-shi, Hyogo, Japan

Takamatsu Red Cross Hospital

🇯🇵

Takamatsu-shi, Kagawa, Japan

Ishikawa Prefectural Central Hospital

🇯🇵

Kanazawa-shi, Ishikawa, Japan

Kagoshima University Hospital

🇯🇵

Kagoshima-shi, Kagoshima, Japan

Nomura Dermatology Clinic

🇯🇵

Yokohama-shi, Kanagawa, Japan

Nagaoka Red Cross Hospital

🇯🇵

Nagaoka-shi, Niigata, Japan

Kochi Medical School Hospital

🇯🇵

Nankoku-shi, Kochi, Japan

Dermatology and Ophthalmology Kume Clinic

🇯🇵

Sakai-shi, Osaka, Japan

Oita University Hospital

🇯🇵

Yufu-shi, Oita, Japan

Medical Corporation Goto Dermatology Clinic

🇯🇵

Osaka-shi, Osaka, Japan

Nippon Life Hospital

🇯🇵

Osaka-shi, Osaka, Japan

Yoshikawa Skin Clinic

🇯🇵

Takatsuki-shi, Osaka, Japan

Dokkyo Medical University Saitama Medical Center

🇯🇵

Koshigaya-shi, Saitama, Japan

Pansy Skin Clinic

🇯🇵

Saitama-shi, Saitama, Japan

Jichi Medical University Hospital

🇯🇵

Shimotsuke-shi, Tochigi, Japan

Tokyo Teishin Hospital

🇯🇵

Chiyoda-ku, Tokyo, Japan

Teikyo University Hospital

🇯🇵

Itabashi-ku, Tokyo, Japan

Yamanashi Prefectural Central Hospital

🇯🇵

Kofu-shi, Yamanashi, Japan

Tokyo Medical University Hospital

🇯🇵

Shinjuku-ku, Tokyo, Japan

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