Trial of HSK44459 Cream for the Management Plaque Psoriasis

A Randomized, Double-Blind, Vehicle-Controlled Phase I/II Clinical Study of HSK44459 Cream in Healthy Subjects and Patients With Plaque Psoriasis

Phase I

Study Objectives:

• Primary: Assess the safety and tolerability of HSK44459 cream in 10 healthy adult participants and 10 patients with plaque psoriasis.
• Secondary: Evaluate the pharmacokinetic (PK) profile of HSK44459 cream in the same populations (healthy adults and plaque psoriasis patients).

Participant Allocation:

- 10 healthy adults and 10 plaque psoriasis patients are enrolled. Participants are randomized to either the HSK44459 cream group (8 per population) or the vehicle (placebo - like) control group (2 per population).

Treatment Schedule:

• Day 1: Single - dose administration (one application).
• Days 2-3: Washout period (no medication).
• Days 4-9: Twice - daily administration.
• Day 10: One application.

Phase II

Study Objectives:

• Primary: Conduct a preliminary evaluation of the efficacy of HSK44459 cream in treating plaque psoriasis.
• Secondary: Assess the safety and tolerability of HSK44459 cream in plaque psoriasis patients.

Evaluate the PK profile of HSK44459 cream in plaque psoriasis patients.

Participant Allocation:

- 160 plaque psoriasis patients are enrolled and randomized in a 1:1:1:1 ratio to four groups: 1% HSK44459 cream (40 patients), 0.3% HSK44459 cream (40 patients), 0.1% HSK44459 cream (40 patients), or vehicle control (40 patients).

Treatment Schedule:

Phase II: The study consists of three phases (screening, treatment, and follow - up)

• Screening Period (D - 28 to D - 1): Eligible plaque psoriasis patients sign an informed consent form and complete screening assessments to establish baseline data.
• Treatment Period (W1D1 to W9D1 ± 3 days): After baseline evaluation, eligible patients are randomized. The first dose of the study drug is administered on W1D1, with twice - daily dosing for 8 weeks. Patients return to the study center at W3D1 ± 3, W5D1 ± 3, W7D1 ± 3, W9D1 ± 3, and W11D1 ± 3 for scheduled assessments and procedures.
• Follow - up Period (W9D1 ± 3 days to W11D1 ± 3 days, within 14 days after the last dose): Adverse events and concomitant medications are collected. A final safety visit (W11D1 ± 3 days) includes additional assessments and procedures.

In summary, this trial aims to comprehensively evaluate HSK44459 cream's potential as a treatment for plaque psoriasis, while also characterizing its safety, tolerability, and PK properties in both healthy individuals and patient populations.

Inclusion Criteria:

Healthy Participants in Phase I Study:

• Able to communicate effectively with researchers, fully understand the study's purpose and requirements, voluntarily participate in the clinical trial, and sign a written informed consent form;
• Age at screening: 18-45 years (inclusive of boundary values), both male and female are eligible;
• Weight at screening: ≥50 kg (males), ≥45 kg (females); body mass index (BMI) between 19.0-27.0 kg/m² (inclusive of boundary values);
• At screening and before drug administration, the skin in the target application area has no ulcers, injuries, sunburn, erythema, papules, pigmentation, uneven skin tone, excessive freckles, or abnormal heat. Participants must agree to shave hair from this skin area (if present) to ensure uniform drug application and to distinguish skin conditions (e.g., edema, erythema, papules, increased temperature).
• The participant (and their partner, if applicable) agrees to have no plans for pregnancy, sperm donation, or egg donation during the study and for 3 months after drug administration. Effective non - pharmacological contraceptive measures (e.g., complete abstinence, condoms, intrauterine devices, partner sterilization) must be used.

Patients with Psoriasis in Phase I and Phase II Studies:

Demographics:

• Fully understand the study, voluntarily participate, and sign the informed consent form;
• Age ≥18 years, gender - unrestricted;
• Able to understand and complete study - related scales, agree to have photographs taken of the lesion area, and comply with follow - up schedules and other protocol requirements.
• At screening: ≥50 kg (males), ≥45 kg (females); BMI between 19-27 kg/m² (inclusive of boundary values). Only applicable to Phase I study

Disease - Related:

• Diagnosed with plaque psoriasis for ≥6 months (as of randomization);
• Plaque psoriasis has been stable in the past 4 weeks, defined as: no morphological changes or severe disease progression (as judged by the investigator).
• Both screening visits and baseline assessments meet the criteria for plaque psoriasis, and the following requirements must be satisfied simultaneously:

Body surface area (BSA) of psoriatic lesions: 2%-20% (inclusive of both endpoints, excluding scalp, palms, and soles); Psoriasis Area and Severity Index (PASI): ≥2 (excluding scalp, palms, and soles); Investigator Global Assessment (IGA): ≥2 points.

-The investigator assesses that the participant is suitable for topical treatment.

Contraception Requirements:

During the entire study period (from signing the informed consent form) and for 3 months after the last dose, women of childbearing potential and male participants who have not undergone vasectomy must use effective contraceptive measures. Effective contraceptive measures include: vasectomy, abstinence, intrauterine device (IUD), hormones (oral, patch, ring, injection, implant), and barrier methods (diaphragm, cervical cap, sponge, condom).

Exclusion Criteria:

Healthy Participants in Phase I Study:

• Those with clinically significant abnormal results in vital signs, physical examination, laboratory tests (routine blood test, biochemical blood test, coagulation function, routine urine test), chest PA X - ray, abdominal color Doppler ultrasound, etc., and deemed unsuitable to participate in this trial by the investigator;

• Those with a history of heart - related diseases such as familial hereditary heart disease, ischemic heart disease, heart failure, malignant arrhythmia, etc.; those with a confirmed history of QTc prolongation; those with the following electrocardiogram (ECG) findings during the screening period:

  1. QT interval corrected by Fridericia's method (QTcF): > 450 ms for male subjects, > 470 ms for female subjects;
  2. Second - degree or third - degree atrioventricular block;
  3. Bundle branch block;
  4. PR interval ≥ 220 ms; or those with ECG results that are judged by the investigator to be clinically significantly abnormal during the screening period;

• Those with a history of major diseases in the cardiovascular, respiratory, digestive, urinary, hematological, endocrine, immune, or nervous systems, or those who underwent major surgery within 3 months before the screening period or whose surgical incisions have not fully healed;

• Those known to be allergic to any component of the investigational drug or formulation, or those with allergic constitutions (e.g., allergic to two or more drugs, foods, or pollens); or those with a history of specific allergies (e.g., asthma, urticaria, eczema, etc.);

• Those with special dietary requirements and unable to comply with a unified diet;

• Those who consumed excessive tea, coffee, or caffeinated beverages (on average more than 4 cups per day, 1 cup = 250 mL) within 3 months before the screening; or those who took tea or any food or beverage containing caffeine (e.g., coffee, chocolate, etc.) within 48 hours before the first dosing; or those who do not agree to stop taking tea, coffee, or caffeinated foods or beverages during the trial;

• Those who ingested a large amount of beverages or foods rich in grapefruit (i.e., pomelo) (e.g., grapefruit, grapefruit juice, grapefruit jam, etc.) within 14 days before the screening; or those who ingested any beverage or food rich in grapefruit (i.e., pomelo) within 48 hours before the first dosing; or those who do not agree to stop drinking any beverage or food rich in grapefruit (i.e., pomelo) during the trial;

• Those with a history of alcohol abuse within 3 months before the screening, i.e., drinking more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of liquor with 40% alcohol content or 150 mL of wine), or those who cannot abstain from alcohol during the trial, or those with a positive alcohol breath test;

• Those who smoked more than 5 cigarettes per day (or used an equivalent amount of nicotine - containing products) within 3 months before the screening, or those who cannot refrain from smoking during the trial;

• Those who donated blood or had blood loss ≥ 400 mL (excluding menstrual blood loss in women) within 3 months before the screening, or plan to donate blood during the study period, or received blood transfusion or used blood products within 3 months before the screening;

• Those who took any prescription drugs, over - the - counter drugs, Chinese herbal medicines, or health supplements within 14 days before the screening or within 5 half - lives of the drug (whichever is longer);

• Those who participated in other clinical trials of drugs within 3 months before the screening; or those who plan to participate in other clinical trials during the trial;

• Those who were vaccinated with a live vaccine (except influenza vaccine) within 1 month before the screening, or those who plan to be vaccinated with a live vaccine during the trial;

• Those with a history of drug abuse, drug misuse, or drug dependence, or those with a positive drug abuse screening;

• Those who have one or more positive test results for hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, and Treponema pallidum antibody during the screening period;

• Those with a history of fear of needles or blood, difficulty in blood collection, or inability to tolerate venipuncture for blood collection;

• Pregnant or lactating women; or those with a positive pregnancy test;

• Those whom the investigator deems to have poor compliance, or those with other factors that make them unsuitable to participate in this trial.