A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Escalation Study in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
This is a single center, randomized, double-blind, placebo-controlled, single and multiple dose escalation phase 1 study. The objective of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneous administered SHR-1819 in healthy subjects

Official Title
-----------------
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Administered SHR-1819 in Healthy Subjects

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: SHR-1819
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to understand the trial procedures and possible adverse events, volunteers to participate in the trial, and provides written informed consent. Be able to comply with all the requirements and able to complete the study. Male or female aged between 18 years and 55 years (inclusive) at the date of signed consent form. No clinically significant abnormalities in medical history, general physical examination, vital signs, and laboratory tests. Men and women of childbearing potential (WOCBP) must agree to take effective contraceptive methods and have no plan to have a child from signing the consent form to 16 weeks after IP administration. Exclusion Criteria: Positive hepatitis B virus (HBsAg), hepatitis C virus (HCV-Ab), human immunodeficiency virus (HIV-Ab), or QuantiFERON-TB Gold tests at screening; Participation in clinical trials of other investigational drugs or medical devices within 3 months prior to screening (according to the date of signed consent form), or in the follow-up period of a clinical study Severe injuries or surgeries within 6 months before screening or plan to do surgeries during the trial Any other circumstances that, in the investigator's judgment, may increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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
Interventional Model Description: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br> | Drug: SHR-1819<br>* SHR-1819 will be subcutaneously administered with different dose levels;<br>|
| Placebo Comparator: Treatment group B<br> | Drug: Placebo<br>* Placebo will be subcutaneously administered with different dose levels;<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence and severity of adverse events | Start of Treatment to end of study（about 13 weeks） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics-AUC0-last | Area under the concentration-time curve from time 0 to last time point after SHR-1819 administration | Start of Treatment to end of study (about 13 weeks) | 
| Pharmacokinetics-AUC0-inf | Area under the concentration-time curve from time 0 to infinity after SHR-1819 administration | Start of Treatment to end of study (approximately 13 weeks) | 
| Pharmacokinetics-Tmax | Time to Cmax of SHR-1819 | Up to 13 weeks | 
| Pharmacokinetics-Cmax | Maximum observed concentration of SHR-1819 | Up to 13 weeks | 
| Pharmacokinetics-CL/F | Apparent clearance of SHR-1819 | Up to 13 weeks | 
| Pharmacokinetics-Vz/F | Apparent volume of distribution during terminal phase of SHR-1819 | Up to 13 weeks | 
| Pharmacokinetics-t1/2 | Terminal elimination half-life of SHR-1819 | Up to 13 weeks | 
| Change from baseline to end of treatment for Thymus and activation-regulated chemokine（TARC/CCL17） | Thymus and activation-regulated chemokine（TARC/CCL17） | Up to 13 weeks | 
| Change from baseline to end of treatment for IgE | IgE | Up to 13 weeks | 
| Immunogenicy of SHR-1819 after administration | Anti-drug antibody | Up to 13 weeks] | 
| Pharmacokinetics-AUCtau for multi-dose | Area under the concentration-time curve from time 0 to last time point after SHR-1819 administration | Start of Treatment to end of study (about 13 weeks) | 
| Pharmacokinetics- Ctrough for multi-dose | Minimum observed concentration of SHR-1819 | Up to 13 weeks | 
| Pharmacokinetics- Racc for multi-dose | Accumulation ratio of SHR-1819 | Up to 13 weeks |