A Phase 2b Study to Evaluate RIST4721 in Palmoplantar Pustulosis (PPP)

Study Overview
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Brief Summary
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A 12-week Randomized, Double-blind, Placebo-controlled, Dose Ranging Phase 2 Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis followed by an Open-label Extension Phase.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Dose Ranging Phase 2 Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects With Palmoplantar Pustulosis

Conditions
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Palmoplantar Pustulosis

Intervention / Treatment
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* Drug: RIST4721
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 6 months history of moderate or severe PPP, as defined by PPPASI ≥12 and PPPGA ≥3 at screening Males and females must be willing to use birth control as indicated Exclusion Criteria: Moderate to severe psoriasis covering ≥10% of total body surface area (BSA) at screening Breastfeeding or pregnant Known immunodeficiency or subject is immunocompromised Active/latent infection with HBV, HCV, HIV, SARS-CoV-2 or TB Any topical medications for PPP excluding emollients within two weeks of randomization and systemic therapies (including phototherapy) within 4 weeks of randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIST4721 400 mg<br>RIST4721 400 mg: 4 active (100 mg) tablets once daily for 12 weeks | Drug: RIST4721<br>* RIST4721 tablets, 100 mg are blue, oval, biconvex film-coated tablets<br>|
| Experimental: RIST4721 200 mg<br>RIST4721 200 mg: 2 active (100 mg) tablets + 2 placebo tablets once daily for 12 weeks | Drug: RIST4721<br>* RIST4721 tablets, 100 mg are blue, oval, biconvex film-coated tablets<br>Drug: Placebo<br>* Matching placebo<br>|
| Placebo Comparator: Placebo<br>Placebo: 4 placebo tablets once daily for 12 weeks | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving a 50% Reduction in PPPASI Score | In the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI), the left palm, right palm, left foot, and right foot are assessed based on 3 target symptoms: erythema, desquamation (scaling), and pustules, as seen on the day of the examination. The severity of each sign is assessed using a 5-point scale (0 = not present, 1 = slight, 3 = moderate, 4 = severe, 5 = very severe). The affected area within a given anatomic site (left palm, right palm, left foot, and right foot) is estimated as a percentage of the total area of that anatomic site and assigned a numerical value according to the degree of PPP involvement (0 = no involvement, 2 = 10 to less than 30% involvement, 3 = 30 to less than 50% involvement, 4 = 50 to less than 70% involvement, 5 = 70 to less than 90% involvement, 6 = 90 to less than 100% involvement). PPPASI score for palms and soles is obtained using a formula and can vary from 0 (absence of disease) to 72 (most severe disease). | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in PPPGA |  | Baseline to Week 12 | 
| Absolute Change From Baseline in PPPASI |  | Baseline to Week 12 |