A Clinical Study of ICP-488 in Healthy Subjects and Patients With Psoriasis

Study Overview
=================
Brief Summary
-----------------
This is a Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single and Multiple AscendingDose Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ICP-488 in Healthy Subjects and Patients With Psoriasis

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single and Multiple AscendingDose Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ICP-488 in Healthy Subjects and Patients With Psoriasis

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Drug: ICP-488
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Voluntarily signed informed consent, and was able to communicate well with the investigator and can complete the study according to the study requirement. Body mass index (BMI) between 18-26 kg/m2, the weight of male subject should not be less than 50 kg, and the weight of female subject should not be less than 45 kg. The results of laboratory tests during the screening period are within the normal reference values of the population or study site;Or the results were slightly off but within acceptable limits, and the investigator evaluated that they were not clinically significant. Fertility status: Female subjects who are infertile (i.e. physically unable to conceive, including postmenopausal or surgically infertile women);Male subjects and their partners must agree to use effective contraception for the entire study period and for 28 days after the last medication or for five half-lives, and male subjects shall not donate sperm during this period. Male or female subjects aged ≥ 18 years and ≤ 65 years； Diagnosis of plaque psoriasis； All of the following 3 criteria are met at screening and randomization: 1）Psoriasis Area and Severity Index (PASI) ≥ 12; 2）Physician Global Assessment (PGA) ≥ 3; 3）Body surface area (BSA) affected by psoriasis ≥ 10%. 8. The subject is a candidate to receive systemic therapy and/or phototherapy. Exclusion Criteria: Unable to follow the study protocol requirements. Evidence or history of clinically significant disease, or evidence or history of allergic disease. Subjects with clinically significant gastrointestinal dysfunction that may affect drug intake, transport or absorption. Acute disease state within 14 days before administration. Currently or within 6 months prior to administration experiencing a severe infection or having a long-term or recurrent infection disease Subjects and/or first-degree relatives have a genetic immune deficiency. Major trauma or surgery within 3 months prior to the first administration. Previous medical history of tuberculosis; The presence of investigator-judged signs or symptoms of active tuberculosis and the chest imaging showed active pulmonary tuberculosis at screening ；T-spoT test (T-SPOT) was positive at screening. Urine drug test positive. Alcoholic Subjects who have used tobacco/cigarettes or tobacco/cigarette products within 3 months prior to the first administration. Subjects who donated more than 500 ml of blood (excluding plasma) within 56 days before the first dose, or planned to donate blood or blood components during the study period or within 1 month after the study finished. Use of any other study drug specified in the protocol within 30 days prior to initial administration or within 5 half-lives(refer to whichever is longer). Any traditional Chinese medicine (TCM) and over-the-counter (OTC) drugs, vitamins, systemic steroid hormone therapy, immunosuppressant or modulator therapy, hormone replacement therapy, and other food supplements or herbs were used 30 days before the first dose until follow-up visit. Consume any food or drink containing caffeine within 48 hours prior your first administration. Last use of stron , moderate and weak CYP1A2/CYP3A4 inhibitors or inducers less than 5 half-lives before the first dose of study drug, or planning to take medications, dietary supplements, or foods Diet or dietary treatment within 30 days prior to initial administration or have significant change in eating habits. Eat smoked charcoal fire foods (such as Carbon barbecue,etc) within 1 week prior to the study. Any positive showed in the lab result of syphilis specific antibody, hepatitis C antibody (HCV-Ab), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or human immunodeficiency virus serological antibody (HIV-Ab) during screening. Received vaccination with live virus vaccine, live attenuated vaccine or any live virus component is administered within 6 weeks prior to initial administration, or during the planned study period or within 8 weeks after the end of the study. Non-plaque forms of psoriasis. Drug-induced psoriasis. Are taking or require oral or injectable corticosteroids for any medical condition. Clinically significant test results at the time of screening that, in the investigator's judgment, may cause unacceptable risk to the participant. History of active tuberculosis，active hepatitis B virus、active hepatitis C virus or Syphilis infection. Clinically severe, progressive, or uncontrolled disease at screening； Pregnant female subjects. breastfeeding female subjects. Other situations judged by the investigator to be unsuitable to join this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICP-488<br>Single ascending doses of ICP-488 tablet; Multiple ascending doses of ICP-488 tablet; Part3 Patients with Psoriasis:ICP-488 tablet. | Drug: ICP-488<br>* ICP-488 will be administered as tablet<br>|
| Placebo Comparator: Placebo<br>Single ascending doses of placebo; Multiple ascending doses of placebo; Part3 Patients with Psoriasis of placebo. | Drug: Placebo<br>* Matching placebo will be administered as tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events during treatment, and withdrawal from treatment due to adverse events |  | Single ascending dose: 1day；Multiple ascending dose: 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | Single ascending dose: 1day；Multiple ascending dose: 28 days | 
| Psoriasis Area and Severity Index （PASI） |  | Day1,Day7,Day14,Day21,Day28,Day35,Day42,Day56 | 
| Body Surface Area （BSA） |  | Day1,Day7,Day14,Day21,Day28,Day35,Day42,Day56 | 
| Static Physician's Global Assessment （sPGA） |  | Day1,Day7,Day14,Day21,Day28,Day35,Day42,Day56 | 
| Peak Pruritus Numerical Rating Scale （PP-NRS） |  | Day1-Day14, Day21, Day28, Day35, Day42, Day56 | 
| Dermatology quality of life index （DLQI） |  | Day1,Day7,Day14,Day21,Day28,Day35,Day42,Day56 |