A Prospective, Interventional, Exploratory Study Evaluating the Efficacy of Small-Molecule Compound XJH05 Ointment in the Treatment of Plaque Psoriasis

I. Background Psoriasis Characteristics: Psoriasis is a chronic, recurrent, inflammatory, and systemic disease mediated by immunity, induced by a combination of genetic and environmental factors. It is clinically characterized by scaly erythema or plaques, non-contagious, difficult to treat, and often lifelong.

Pathogenesis & Cellular Mechanisms: Driven by T lymphocyte-mediated and multi-immune cell-involved responses, causing hyperproliferation of keratinocytes and joint/synovial/chondrocyte inflammation.

Current Unmet Medical Needs: Plaque psoriasis accounts for ~90% of cases, and ~80% are mild (≤2% BSA) primarily managed with topical agents (e.g., vitamin "D" _3 derivatives, glucocorticoids, retinoids). Although many therapies exist, psoriasis remains incurable.

Mechanism of XJH05: Recent studies show the LCN2/SLC22A17 axis activates the SREBP2 pathway to induce keratinocyte cholesterol metabolism dysfunction, acting synergistically with the NLRC4 inflammasome to release IL-1$\\beta$ and IL-18 and recruit neutrophils. Direct SLC22A17 inhibitors are lacking in current clinical development.

Investigational Drug: XJH05 is a novel small-molecule compound that specifically binds to the SLC22A17 active site, blocking LCN2 binding and inhibiting the LCN2-SREBP2-NLRC4 signaling axis. Preclinical animal studies and in vitro human lesion assays demonstrated excellent safety and efficacy, but clinical evaluation of XJH05 ointment in patients is needed.

II. Study Objectives

• Primary Objective: To evaluate the therapeutic efficacy of XJH05 ointment in patients with plaque psoriasis in a prospective clinical setting.
• Secondary Objectives:

To assess the safety, local tolerability, and incidence of adverse events (AEs) associated with topical XJH05 ointment application.

To observe improvements in lesion severity, affected body surface area (BSA), and patient quality of life.

III. Study Design & Procedures

• Study Type: A prospective, interventional, exploratory clinical trial.
• Dosing Protocol: Topical application of XJH05 ointment on target lesions for a defined treatment duration (e.g., 4-12 weeks, as specified by trial protocol).
• Key Study Phases:

• Screening/Run-in Phase: Patient eligibility assessment and baseline scoring.
• Treatment Phase: Standardized topical application of XJH05 ointment with periodic follow-up evaluations.
• Follow-up Phase: Post-treatment safety and relapse observation. IV. Patient Selection

• Inclusion Criteria:

• Diagnosis of plaque psoriasis.
• Mild-to-moderate disease presentation suitable for topical intervention (e.g., ≤2% to 10% BSA).
• Provision of written informed consent prior to study procedures. 2. Exclusion Criteria:
• Non-plaque subtypes (e.g., erythrodermic, pustular, or generalized guttate psoriasis).
• Recent use of systemic antipsoriatic therapies, biologics, or topical steroids/retinoids within the protocol-defined washout period.
• Active localized skin infection at target sites or known hypersensitivity to XJH05 or ointment ingredients.

V. Methods & Technical Route

• Preclinical to Clinical Translation:

-Target Verification: Blockade of the SLC22A17 receptor active site → inhibition of LCN2 interaction → downregulation of the LCN2-SREBP2-NLRC4 signaling pathway → reduction of pro-inflammatory cytokines (IL-1B, IL-18) → prevention of keratinocyte hyperproliferation and neutrophil infiltration.

• Trial Execution Route:

• Screening & Informed Consent → Baseline Clinical & Biomarker Evaluation →Intervention (XJH05 Ointment Application) → Serial Follow-ups & Outcome Measurement → Statistical Analysis & Translation Assessment.

VI. Outcome Measures & Follow-Up Timing

• Primary Outcome Measures:

• Proportion of patients achieving PASI-75 / PASI-50 (Psoriasis Area and Severity Index) improvement from baseline.
• Investigator's Global Assessment (IGA) score change/clearance rate.
• Secondary Outcome Measures:

• Change in Body Surface Area (BSA) affected.
• Patient-reported outcomes (e.g., Dermatology Life Quality Index / DLQI).
• Reduction in local inflammatory biomarkers (if lesion biopsies/swabs are performed).
• Follow-Up Timing:

• Periodic clinic visits scheduled at Baseline (Week 0), Week 2, Week 4, Week 8, and Week 12 (or end-of-treatment / follow-up evaluation).

VII. Adverse Event Monitoring

• Safety Assessments: Continuous evaluation of local application site reactions (e.g., erythema, burning, pruritus, scaling, irritation) and systemic toxicity throughout the trial.
• AE/SAE Reporting: Documentation of all Treatment-Emergent Adverse Events (TEAEs), severity grading (CTCAE standard), causality assessment, and immediate reporting for Any Serious Adverse Events (SAEs).

VIII. Statistical Analysis SPSS 26.0 software for data analysis; compare efficacy/safety between groups using appropriate statistical methods.

• Inclusion Criteria:

• Diagnosis of plaque psoriasis.
• Mild-to-moderate disease presentation suitable for topical intervention (e.g., ≤2% to 10% BSA).
• Provision of written informed consent prior to study procedures.
• Exclusion Criteria:

• Non-plaque subtypes (e.g., erythrodermic, pustular, or generalized guttate psoriasis).
• Recent use of systemic antipsoriatic therapies, biologics, or topical steroids/retinoids within the protocol-defined washout period.
• Active localized skin infection at target sites or known hypersensitivity to XJH05 or ointment ingredients.