An Efficacy and Safety of Guselkumab in Participants With Palmoplantar Pustulosis

Palmoplantar Pustulosis Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Guselkumab for the Treatment of Subjects With Palmoplantar Pustulosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02641730
• Other study ID #: CR108046
• Secondary ID: CNTO1959PPP3001
• Status: Completed
• Phase: Phase 3
• Start date: December 15, 2015
• Est. completion date: July 17, 2018

Study information

• Verified date: July 2019
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of guselkumab for the treatment of participants with palmoplantar pustulosis.

Description:

This is a phase 3, randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), multicenter (when more than one hospital works on a medical research study) placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study) study in participants with palmoplantar pustulosis. The study will consist of 3 phases: screening phase (up to 6 weeks), treatment period (week 0 - week 60) and observational period (up to week 84). Participants will be assigned to 1 of 3 treatment groups (200 milligram [mg] guselkumab, 100 mg guselkumab or placebo group) using a stratified block randomization method in a 1:1:1 ratio at Week 0 and Group III (placebo) participants will be allocated in a 1:1 ratio to 1 of 2 treatment groups at Week 16. Participants will primarily be assessed for change from baseline in Palmo-Plantar Pustular Area and Severity Index (PPPASI) total score at Week 16. Safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: July 17, 2018
• Est. primary completion date: March 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Has a diagnosis of palmoplantar pustulosis (with or without pustulotic arthro-osteitis, concurrent extra-palmoplantar lesions) for at least 24 weeks before screening

• Has a >= 12 PPPASI total score at screening and at baseline

• Has a moderate or more severe pustules/vesicle on the palms or soles (>= 2 PPPASI severity score) at screening and baseline

• Has inadequate response to the treatment with topical steroid and/or topical vitamin D3 derivative preparations and/or the phototherapy and/or systemic etretinate prior to or at screening. Inadequate response is defined as a case judged by the investigator

• Before the first administration of study drug, a woman must be either: Not of childbearing potential: premenarchal; postmenopausal or Of childbearing potential and practicing a highly effective method of birth control

Exclusion Criteria:

• Has a diagnosis of plaque-type psoriasis

• Has obvious improvement during screening (>= 5 PPPASI total score improvement during the screening)

• Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances

• Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable angina, rapid atrial fibrillation) in the last 12 weeks or a cardiac hospitalization within the last 12 weeks before screening

• Currently has a malignancy or has a history of malignancy within 5 years before screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 12 weeks before screening or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 12 weeks before screening)

Related Conditions & MeSH terms

• Palmoplantar Pustulosis
• Psoriasis

Intervention

Drug:
• Guselkumab
Participants will receive two or one syringe of guselkumab 100 mg subcutaneously at Week 0, 4, 12 and every 8 weeks thereafter through Week 60 in group 1 or 2. Group 3a or 3b participants will receive two or one syringe of guselkumab 100 mg at Week 16, 20 and every 8 weeks thereafter through Week 60.
• Placebo
Participants in group 1 will receive placebo at Week 16. Participants in group 2 will receive placebo at Week 0, 4, 12, 16, 20 and every 8 weeks thereafter through Week 60. Participants in group 3 will receive placebo at Week 0, 4, 12, then at Week 16, 20 and every 8 weeks thereafter through Week 60 for group 3b.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Palmoplantar Pustulosis Area and Severity Index (PPPASI) Total Score at Week 16	PPPASI assesses severity of palmoplantar pustulosis (PPP) lesions and response to therapy. In PPPASI, palms, soles are divided into 4 regions: right palm(RP), left palm(LP), right sole(RS), left sole(LS), that account for 20 percent (%), 20%,30%,30%, respectively, of total surface area(TSA) of palms, soles. Each area is assessed separately for erythema(E), pustules/vesicles (P), desquamation/scales (D), each rated on a scale (0-4). PPPASI produces score range of 0-72 using formula, PPPASI=(E+P+D)Area*0.2(RP)+(E+P+D)Area*0.2 (LP)+(E+P+D)Area*0.3(RS)+(E+P+D)Area*0.3(LS). Higher a score more the severe disease. Participants who discontinue study agent as they met treatment failure(TF) criterion(lack of efficacy/AE of worsening of PPP/who started a protocol-prohibited medication/therapy that could improve PPP), their baseline value carried forward to post baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline and Week 16
Secondary	Change From Baseline in Palmoplantar Severity Index (PPSI) Total Score at Week 16	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline and Week 16
Secondary	Percentage of Participants Who Achieved a PPPASI-50 Response at Week 16	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, that account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-50 response represents participants who achieved at least a 50% improvement from baseline in the PPPASI score. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 16
Secondary	Change From Baseline in PPPASI Total Score	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, which account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-50 response represents participants who achieved at least a 50% improvement from baseline in the PPPASI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Change From Baseline in PPSI Total Score	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPPASI-50 Response	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, that account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-50 response represents participants who achieved at least a 50% improvement from baseline in the PPPASI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPPASI-75 Response	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, that account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-75 response represents participants who achieved at least a 75% improvement from baseline in the PPPASI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as nonresponders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPPASI-90 Response	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, that account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-90 response represents participants who achieved at least a 90% improvement from baseline in the PPPASI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPPASI-100 Response	PPPASI assesses severity of PPP lesions and their response to therapy. In PPPASI system, palms and soles are divided into 4 regions: right palm, left palm, right sole, and left sole, that account for 20%, 20%, 30%, and 30%, respectively, of TSA of palms and soles. Each of these areas is assessed separately for erythema, pustules/vesicles, and desquamation/scales, each rated on a scale of 0 to 4. PPPASI produces a score range from 0 to 72. Higher score indicates more severe disease. PPPASI-100 response represents participants who achieved at least a 100% improvement from baseline in the PPPASI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPSI-50 Response	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPSI-75 Response	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPSI-90 Response	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. PPSI 90 response represents participants who achieved at least a 90% improvement from baseline in the PPSI score. Participants were analyzed according to the treatment at Week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PPSI-100 Response	PPSI assesses the severity of PPP lesions and their response to therapy with a score ranging from 0 to 12. A higher score indicates more severe disease. In the PPSI system, the more severely affected location (palms or soles) were to be identified as the evaluation sites at screening that to be assessed at all subsequent visits. Evaluation sites were assessed separately for erythema, pustules/vesicles and desquamation/scale, for most severe skin lesion rated on a scale of 0 to 4. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 72 and Week 84
Secondary	Percentage of Participants in Each Categories of Physician's Global Assessment (PGA) Score	The PGA documents the Physician's Global Assessment of the PPP overall skin lesions status. The participant's PPP is assessed as clear (0), almost clear (1), mild (2), moderate (3), severe (4), or very severe (5). Participants were analyzed according to the treatment at week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders at week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PGA Score of Cleared (0) or Almost Cleared (1)	The PGA documents the Physician's Global Assessment of the participant's palmoplantar overall skin lesions status. The participant's PPP is assessed as clear (0), almost clear (1), mild (2), moderate (3), severe (4), or very severe (5). Participants who achieved a PGA score of clear (0) or almost clear (1) were reported. Participants were analyzed according to the treatment at week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders through Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Percentage of Participants Who Achieved a PGA Score of Cleared (0) or Almost Cleared (1) and Had at Least a 2-Grade Improvement	The PGA documents the Physician's Global Assessment of the participant's palmoplantar overall skin lesions status. The participant's PPP is assessed as clear (0), almost clear (1), mild (2), moderate (3), severe (4), or very severe (5). Participants who achieved a PGA score of clear (0) or almost clear (1) and had at least a 2-grade improvement from baseline were reported. Participants were analyzed according to the treatment at week 0 or 16. Participants who discontinue study agent as they met a TF criterion were considered as non-responders through Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84
Secondary	Change From Baseline in the Dermatology Life Quality Index (DLQI) Score	The DLQI is a dermatology-specific quality of life (QOL) instrument designed to assess the impact of the disease on a participant's QOL. It is a 10-item participant-reported outcome questionnaire that, in addition to evaluating overall QOL, can be 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 that can range from 0 to 30. Higher score indicates more severe disease. Participants were analyzed according to the treatment at week 0 or 16. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to the post-baseline attending visits before and at Week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 16, 32, 52, 72 and Week 84
Secondary	Change From Baseline in the 36-Item Short-Form Health Assessment Questionnaire (SF-36) Physical Component Summary (PCS) Score	SF-36 consists of 8 individual domains, which are weighted sums of questions in their section. 8 domains are: vitality(VT), physical functioning(PF), bodily pain(BP), general health(GH), Role-Physical(RP), Role-Emotional(RE), social functioning(SF) and mental health(MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on scale scores, summary PCS is derived. Scales contributing most to the scoring of the SF-36 PCS include PF,RP,BP and GH. Other domains not noted contribute to scoring but to a lesser degree. Scoring is derived based on an algorithm as presented in Japanese edition manual. Summary PCS score is also scaled from 0 to 100 with higher scores indicating better health. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to post-baseline attending visits before and at week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 16, 32, 52, 72 and Week 84
Secondary	Change From Baseline in the 36-Item Short-Form Health Assessment Questionnaire (SF-36) Mental Component Summary (MCS) Score	SF-36 consists of 8 individual domains, which are weighted sums of questions in their section. 8 domains are: vitality(VT), physical functioning(PF), bodily pain(BP), general health(GH), Role-Physical(RP), Role-Emotional(RE), social functioning(SF) and mental health(MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on scale scores, summary PCS is derived. Scales contributing most to the scoring of the SF-36 PCS include PF,RP,BP and GH. Other domains not noted contribute to scoring but to a lesser degree. Scoring is derived based on an algorithm as presented in Japanese edition manual. Summary PCS score is also scaled from 0 to 100 with higher scores indicating better health. Participants who discontinue study agent as they met a TF criterion, their baseline value carried forward to post-baseline attending visits before and at week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 16, 32, 52, 72 and Week 84
Secondary	Change From Baseline in the EuroQOL-5 Dimensions Questionnaire Visual Analogue Scale (EQ-5D VAS) Score	EQ-5D is designed for self-completion by participants and consists of EQ-5D descriptive system and the EQ visual analog scale (EQ VAS). The EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and unable. The EQ VAS records the respondent's self-rated health on a vertical, VAS where the endpoints are labeled 'Best imaginable health state' (score of 100) and 'Worst imaginable health state' (score of 0). Participants were analyzed according to the treatment at week 0 or 16. Participants who discontinue study agent as they met a TF criterion their baseline value carried forward to the post-baseline attending visits before and at week 16 and after TF were applied, remaining missing data were handled with LOCF till Week 60.	Baseline, Week 16, 32, 52, 72 and Week 84