Safety and Efficacy of HPP737 in Adult Patients With Plaque Psoriasis

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of Oral HPP737 in Adult Patients With Moderate-to-severe Plaque Psoriasis

The goal of this clinical trial is to learn if drug HPP737 works to treat moderate-to-severe plaque psoriasis in adults. It will also learn about the safety of drug HPP737. The main questions it aims to answer are:

Does drug HPP737 improve psoriasis severity compared to placebo, as measured by the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at Day 85? What medical problems do participants have when taking drug HPP737? Researchers will compare drug HPP737 to a placebo (a look-alike substance that contains no drug) to see if drug HPP737 works to treat moderate-to-severe plaque psoriasis.

Participants will:

Take drug HPP737 or a placebo orally every day Visit the clinic regularly for checkups and tests throughout the study Have their psoriasis severity assessed using standardized scoring tools (PASI, Physician's Global Assessment (PGA), and Body Surface Area ( BSA)) This is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial. Eligible participants are adults aged 18 to 70 years with chronic plaque psoriasis for at least 6 months and moderate-to-severe disease at screening.

Inclusion Criteria:

• Subjects must voluntarily sign informed consent before any study-related procedures are initiated, be able to communicate effectively with the investigator, and be able to understand and comply with the requirements of this trial.
• Age at the time of signing the informed consent: 18 years ≤ age ≤ 70 years, regardless of gender.
• A documented history of chronic plaque psoriasis for ≥ 6 months.
• Moderate-to-severe plaque psoriasis meeting all of the following criteria: a) PASI (Psoriasis Area and Severity Index) score ≥12; and b) PGA (Physician's Global Assessment) score ≥3; and c) BSA (Body Surface Area) score ≥10%.
• Subjects are considered suitable for systemic therapy and/or phototherapy and/or photochemotherapy for psoriasis by the investigator.
• Body Mass Index (BMI): 18 kg/m2 ≤ BMI ≤ 35 kg/m2.

Exclusion Criteria:

• At screening, diagnosis of psoriasis is not chronic plaque-type psoriasis (e.g., pustular psoriasis, erythrodermic psoriasis, or guttate psoriasis).
• Patients with drug-induced psoriasis (triggered by medications such as β-blockers [beta-receptor blocking agents], calcium channel inhibitors [calcium channel blockers], or lithium) are included.
• Had a serious or systemic infection within 8 weeks before baseline that required intravenous anti-infective treatment or hospitalization due to infection.
• Presence of other dermatological conditions considered by the investigator to interfere with psoriasis assessment (e.g., skin bacterial, fungal, or viral infections; seborrheic dermatitis).
• History of inflammatory bowel disease or concurrent other active autoimmune diseases.
• History or symptoms of malignancy in any organ system within 5 years prior to screening, whether or not treated, and regardless of evidence of recurrence or metastasis.
• Subjects with a history of depression and/or who exhibit suicidal ideation or any suicidal behavior during the screening period and at baseline as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS, Posner K et al, 2011) will be excluded. If a subject answers "Yes" to any item on the C-SSRS questionnaire, or if the investigator clinically determines the subject to be at risk, the subject will be excluded from the study.
• Donation of blood or blood loss ≥400 mL within 8 weeks prior to baseline and/or planned blood donation during the study period.
• History of moderate-to-severe heart failure (New York Heart Association [NYHA] functional classification ≥Class 3), cardiovascular or cerebrovascular event, or other severe adverse events within 3 months prior to screening, and the investigator determines that such subjects are not suitable for participation in this clinical study.
• Any clinical condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this clinical trial.
• Known allergy to any component or excipient of the investigational product, or hypersensitivity to other biological agents.
• Concomitant use of any of the following psoriasis treatments/medications: a) Tumor necrosis factor alpha (TNF-α) antagonist: ① Prior use of a single TNF-α antagonist (for example: use of adalimumab or infliximab within 60 days prior to baseline; use of golimumab within 90 days prior to baseline; use of etanercept within 28 days prior to baseline); ② or prior use of two or more TNF-α antagonists before screening. b) History of the use of other biologic agents prior to screening: including but not limited to anti-interleukin 17 (IL-17) agents, anti-IL-17 receptor agents, anti-IL-12/IL-23 class of drugs; c) Phototherapy/photochemotherapy (including psoralen plus ultraviolet A [PUVA] therapy, ultraviolet B [UVB], or systemic therapies [e.g., methotrexate, cyclosporine, cyclophosphamide, etc.]) within 4 weeks prior to baseline; d) Within 2 weeks prior to baseline, subjects received topical treatment for psoriasis, such as medium to high-potency corticosteroids, vitamin D3 derivatives, or retinoids; however, the following topical treatments are permitted: low-potency corticosteroids (potency classes 6-7), non-medicated shampoos (i.e., those not containing corticosteroids, vitamin D3 derivatives, calcineurin inhibitors, etc.), and emollients without α- or β-hydroxy acids. Received traditional Chinese medicine (TCM) therapy for psoriasis within 2 weeks before baseline.
• Use of oral or injectable glucocorticoids within 2 weeks before baseline.