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
Overview
- Phase
- Phase 3
- Intervention
- Guselkumab
- Conditions
- Palmoplantar Pustulosis
- Sponsor
- Janssen Pharmaceutical K.K.
- Enrollment
- 159
- Primary Endpoint
- Change From Baseline in Palmoplantar Pustulosis Area and Severity Index (PPPASI) Total Score at Week 16
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of guselkumab for the treatment of participants with palmoplantar pustulosis.
Detailed 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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
Group 1
Participants will receive guselkumab 200 milligram (mg) at Week 0, 4, 12 and every 8 weeks thereafter through Week 60, and two syringes of placebo at Week 16 to maintain the blind.
Intervention: Guselkumab
Group 1
Participants will receive guselkumab 200 milligram (mg) at Week 0, 4, 12 and every 8 weeks thereafter through Week 60, and two syringes of placebo at Week 16 to maintain the blind.
Intervention: Placebo
Group 2
Participants will receive a syringe of guselkumab 100 mg and a syringe of placebo for guselkumab at Week 0, 4, 12 and every 8 weeks thereafter through Week 60, two syringes of placebo at Week 16 to maintain the blind.
Intervention: Guselkumab
Group 2
Participants will receive a syringe of guselkumab 100 mg and a syringe of placebo for guselkumab at Week 0, 4, 12 and every 8 weeks thereafter through Week 60, two syringes of placebo at Week 16 to maintain the blind.
Intervention: Placebo
Group 3
Participants will receive two syringes of placebo at Week 0, 4 and 12. At Week 16, placebo participants will be randomized in a 1:1 ratio to guselkumab mg arm (Group 3a) or 100 mg arm (Group 3b). Group 3a participants will receive guselkumab 200 mg at Week 16, 20 and every 8 weeks thereafter through Week 60. Group 3b participants will receive guselkumab 100 mg and a syringe of placebo at Week 16, 20 and every 8 weeks thereafter through Week 60.
Intervention: Guselkumab
Group 3
Participants will receive two syringes of placebo at Week 0, 4 and 12. At Week 16, placebo participants will be randomized in a 1:1 ratio to guselkumab mg arm (Group 3a) or 100 mg arm (Group 3b). Group 3a participants will receive guselkumab 200 mg at Week 16, 20 and every 8 weeks thereafter through Week 60. Group 3b participants will receive guselkumab 100 mg and a syringe of placebo at Week 16, 20 and every 8 weeks thereafter through Week 60.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Palmoplantar Pustulosis Area and Severity Index (PPPASI) Total Score at Week 16
Time Frame: Baseline and 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.
Secondary Outcomes
- Change From Baseline in Palmoplantar Severity Index (PPSI) Total Score at Week 16(Baseline and Week 16)
- Percentage of Participants Who Achieved a PPPASI-50 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPPASI-75 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPPASI-90 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPSI-75 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPPASI-50 Response at Week 16(Week 16)
- Change From Baseline in PPPASI Total Score(Baseline, Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Change From Baseline in PPSI Total Score(Baseline, Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPPASI-100 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPSI-50 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPSI-90 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PPSI-100 Response(Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, 52, 72 and Week 84)
- Percentage of Participants in Each Categories of Physician's Global Assessment (PGA) Score(Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PGA Score of Cleared (0) or Almost Cleared (1)(Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Percentage of Participants Who Achieved a PGA Score of Cleared (0) or Almost Cleared (1) and Had at Least a 2-Grade Improvement(Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72 and Week 84)
- Change From Baseline in the Dermatology Life Quality Index (DLQI) Score(Baseline, Week 16, 32, 52, 72 and Week 84)
- Change From Baseline in the 36-Item Short-Form Health Assessment Questionnaire (SF-36) Physical Component Summary (PCS) Score(Baseline, Week 16, 32, 52, 72 and Week 84)
- Change From Baseline in the 36-Item Short-Form Health Assessment Questionnaire (SF-36) Mental Component Summary (MCS) Score(Baseline, Week 16, 32, 52, 72 and Week 84)
- Change From Baseline in the EuroQOL-5 Dimensions Questionnaire Visual Analogue Scale (EQ-5D VAS) Score(Baseline, Week 16, 32, 52, 72 and Week 84)