A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of Oral HPP737 in Adult Patients With Moderate-to-severe Plaque Psoriasis.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 515
- 试验地点
- 51
- 主要终点
- To evaluate the proportion of subjects who achieve PASI 75 (a ≥ 75% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）from baseline to Week 16
研究概览
简要总结
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 a placebo at Week 16, as measured by the proportion of patients achieving a significant reduction in the Psoriasis Area and Severity Index (PASI) score? 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.
This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial. 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, including the Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), and Body Surface Area (BSA) Eligible participants are adults aged 18 years and older with a confirmed diagnosis of chronic plaque psoriasis for at least 6 months and moderate-to-severe disease at screening.
详细描述
HPP737-Psoriasis-301 is a phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy and safety of oral HPP737 in adult patients with moderate-to-severe plaque psoriasis. The study is sponsored by Newsoara Biopharma Co., Ltd. The trial involves approximately 504 patients across multiple centers nationwide.
HPP737 is a novel, potent, orally administered, and selective phosphodiesterase type 4 (PDE4) inhibitor. PDE4 is a validated therapeutic target for inflammatory diseases including psoriasis. By inhibiting PDE4, HPP737 raises intracellular cyclic adenosine monophosphate (cAMP) levels, thereby exerting broad anti-inflammatory effects. Preclinical and clinical data have demonstrated that HPP737 potently inhibits interleukin-23 (IL-23) and tumor necrosis factor alpha (TNF-α) production both in vitro and in vivo. Notably, HPP737 has shown a favorable safety and tolerability profile in phase I studies, with no dose-limiting gastrointestinal side effects-such as nausea, vomiting, or diarrhea-commonly associated with other PDE4 inhibitors.
This is a randomized, double-blind, placebo-controlled, parallel-group trial. Eligible patients are adults aged ≥18 years with a confirmed diagnosis of stable chronic plaque psoriasis for ≥6 months and moderate-to-severe disease at screening, defined by Psoriasis Area and Severity Index (PASI) score ≥12, static Physician's Global Assessment (sPGA) score ≥3, and body surface area (BSA) involvement ≥10%. Patients are randomized in a 1:1:1 ratio to one of three treatment arms: HPP737 10 mg once daily, HPP737 20 mg once daily, or placebo.
The total treatment duration is 52 weeks, divided into two phases:
Core Phase (Weeks 0-16): Patients receive double-blind treatment with HPP737 10 mg, HPP737 20 mg, or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily sign the informed consent form before initiation of any study-related procedures, are able to communicate effectively with investigators, and understand and comply with all requirements of this study;
- •Age at signing informed consent: age ≥18 years, regardless of gender;
- •Diagnosed with a history of chronic plaque psoriasis (Psoriasis vulgaris) and disease stability for ≥6 months prior to screening;
- •Diagnosed with moderate to severe plaque psoriasis (Psoriasis vulgaris), and at screening meets the following requirements: 1) PASI (Psoriasis Area and Severity Index) score ≥ 12; and 2) Static Physician Global Assessment (sPGA) score ≥ 3; and 3) Body Surface Area (BSA) involvement ≥ 10%;
- •Body Mass Index (BMI): 18 kg/m2 ≤ BMI ≤ 35 kg/m2
排除标准
- •At screening, diagnosis of psoriasis types other than chronic plaque psoriasis (Psoriasis vulgaris), e.g., pustular psoriasis (Psoriasis pustulosa), erythrodermic psoriasis (Psoriasis erythrodermica), and guttate psoriasis (Psoriasis guttata);
- •Patients with drug-induced psoriasis (including but not limited to new-onset or exacerbation of psoriasis caused by β-blockers [beta-blockers], calcium channel inhibitors [calcium channel blockers], or lithium preparations [lithium salts]);
- •Subjects have other skin diseases that may interfere with clinical assessment (e.g., bacterial, fungal, or viral skin infections, seborrheic dermatitis), chronic diarrhea, severe digestive diseases (such as active gastric ulcer, gastrointestinal tract disorders), or history of inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other active autoimmune inflammatory diseases (mixed connective tissue disease, idiopathic inflammatory myopathy); Note: Chronic diarrhea is defined as disease course >4 weeks, or recurrent diarrhea in a 2-4 week interval. Diarrhea refers to defecation significantly exceeding usual frequency (>3 times/day), stool consistency is loose, water content (>85%), and stool may contain mucus, pus, blood, or undigested food.
- •History of congenital or acquired immunodeficiency;
- •Severe infection or systemic infection within 4 weeks prior to randomization requiring oral and/or intravenous antimicrobial treatment, or hospitalization due to infection;
- •At screening, subject's history, symptoms, and examination results indicate active tuberculosis;
- •History of moderate-to-severe heart failure (New York Heart Association [NYHA] functional classification ≥ Class 3), or occurrence of cardiovascular or cerebrovascular events or severe events within 3 months prior to randomization, such that investigators consider these subjects unsuitable for participation in this clinical trial;
- •History of malignancy in any organ system within 5 years prior to randomization, except for malignancies with low risk of metastasis and mortality, such as adequately treated carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin;
- •Subjects with a history of depression and/or, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) during the screening and baseline period, with ideation or any behavior (see Appendix 6). Subjects who answer "yes" to any question on the C-SSRS questionnaire, or those deemed at risk by the investigator's clinical judgment, will be excluded;
- •Presence of clinically significant, progressive, or uncontrolled disease during the screening period, including but not limited to respiratory, cardiovascular, endocrine, hematologic, skeletal, or neurologic systems, as assessed by the investigator to pose unacceptable risk for participation or interfere with data interpretation;
- •Prior to screening, use of the following psoriasis treatment modalities/drugs: 1) Received topical treatment for psoriasis within 2 weeks prior to randomization, such as glucocorticoids, vitamin D3 derivatives, retinoids, etc.; however, the subject is permitted to use the following topical treatments: non-medicated shampoos and emollients (i.e., those not containing glucocorticoids or vitamin D3 derivatives); Received phototherapy/photochemotherapy (including but not limited to psoralen plus ultraviolet A [PUVA] therapy, ultraviolet B [UVB]), or non-biological systemic therapy (including but not limited to systemic glucocorticoids, leflunomide, cyclophosphamide, azathioprine, methotrexate, cyclosporine, retinoids, mycophenolate mofetil, traditional Chinese medicine for the treatment of psoriasis, or other small-molecule targeted agents for the treatment of psoriasis) within 4 weeks prior to randomization; Tumor necrosis factor-alpha (TNF-α) antagonist: (1) The patient has used at least one TNF-α antagonist within the specified time period prior to randomization (for example, adalimumab, infliximab, golimumab, etanercept, or certolizumab pegol within 12 weeks prior to randomization); (2) or the patient has used two or more TNF-α antagonists prior to randomization; 4) Used other biologic agents within 24 weeks prior to randomization, including but not limited to anti-interleukin-17 (anti-IL-17) inhibitors, anti-interleukin-23 (anti-IL-23) inhibitors, anti-interleukin-12/interleukin-23 (anti-IL-12/23) inhibitors, and related agents;
- •Receipt of live attenuated vaccines within 12 weeks prior to randomization, or planned vaccination with live attenuated vaccines during the study period;
- •Subjects who have previously used other PDE4 inhibitors (such as apremilast, Hemay005, etc.);
研究组 & 干预措施
Placebo (cross over to HPP737 20mg at Week 17)
Specification: 10 mg Administration and dosage: Two capsules (two with 10 mg placebo) are administered orally once daily for a total duration of 16 weeks.
Then patients will be crossed over to receive HPP737 20 mg once daily starting at Week 17 and continuing through Week 52.
干预措施: Placebo matching HPP737 (Drug)
结局指标
主要结局
To evaluate the proportion of subjects who achieve PASI 75 (a ≥ 75% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）from baseline to Week 16
时间窗: From enrollment to end of treatment at 16 weeks
次要结局
- To evaluate the change from baseline in DLQI and the percent change from baseline at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the proportion of subjects who achieve a static Physician's Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) and who have a reduction of ≥2 points from baseline to Week 16.(From enrollment to end of treatment at 16 weeks)
- To evaluate the change from baseline in BSA and the percent change from baseline at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the proportion of subjects who achieve PASI 75 (a ≥ 75% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）from baseline to Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks)
- To evaluate the proportion of subjects who achieve PASI 50 (a ≥ 50% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the proportion of subjects who achieve PASI 90 (a ≥ 90% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）from baseline to Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the proportion of subjects who achieve PASI 100 (a ≥ 100% reduction (improvement) in the Psoriasis Area and Severity Index (PASI) score ）from baseline to Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the change from baseline in PASI(Psoriasis Area and Severity Index) score and the percent change from baseline at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the proportion of subjects who achieve a sPGA score of 0 (clear) or 1 (almost clear) and who have a reduction of ≥2 points from baseline at Week 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, and 52.(From enrollment to end of treatment at 2, 4, 8, 12, 20, 24, 28, 32, 36, 40, 44, 48, and 52 weeks.)
- To evaluate the incidence and severity of adverse events.(From ICF signed to end of study follow-up (at 54 weeks).)
- To evaluate the pharmacokinetic profile (including plasma concentrations and derived parameters) over time at Weeks 0, 2, 4, 8, and 12.(From enrollment to end of treatment at 2,4,8,12 weeks)