A Trial of SHR-1905 in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, single dose escalation phase 1 study. The objective of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of subcutaneous administered SHR-1905 in healthy subjects.

Detailed Description
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The study will consist of one dose esclation part with a total of 5 dose levels. The Subjects will be randomized to receive SHR-1905 as reflected by the guiding principle for the dose esclation/expansion phase. Each dose group includes a screening period, a baseline period, an observational period, and a safety follow-up period.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Single Subcutaneous Administered SHR-1905 in Healthy Subjects

Conditions
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Asthma

Intervention / Treatment
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* Drug: SHR-1905
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the trial procedures and possible adverse events, volunteers to participate in the trial. Male or female aged between 18 years and 55 years (inclusive) at the date of signed consent form. Total body weight ≥45 kg at screening, and body mass index (BMI) between 18 and 28 kg/m2 (inclusive). For healthy subjects, no clinically significant abnormalities. Men and women of childbearing potential (WOCBP) must agree to take effective contraceptive methods Exclusion Criteria: Known medical history of severe disease in cardiovascular, liver, kidney, digestive tract, mental nerve, hematology, metabolic disorders, etc. Severe injuries or major surgeries within 6 months before screening. Subjects with infecious disease. Hyper/Hypotension at screening and at check in. Clinically significant abnormalities in 12-Lead ECG More than 5 cigarettes daily (or products with equivalent amount of nicotine) for 3 months prior to screening Positive urine drug screen . Subject who cannot perform venous blood sampling. Known history or suspected of being allergic to the study drugs and their excipients. Use of any medicine within 4-weeks or within 5 half-lives History of alcohol abuse within 3 months prior to the IP administration . Participation in clinical trials of other investigational drugs or medical devices within 3 months prior to screening in the investigator's judgment, may increase the risk to the subject

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1905 Dose Level 1<br>SHR-1905 Dose level 1 | Drug: SHR-1905<br>* SHR-1905 will be injected subcutaneously<br>Drug: Placebo<br>* Placebo will be injected subcutaneously<br>|
| Experimental: SHR-1905 Dose Level 2<br>SHR-1905 Dose level 2 | Drug: SHR-1905<br>* SHR-1905 will be injected subcutaneously<br>Drug: Placebo<br>* Placebo will be injected subcutaneously<br>|
| Experimental: SHR-1905 Dose Level 3<br>SHR-1905 Dose level 3 | Drug: SHR-1905<br>* SHR-1905 will be injected subcutaneously<br>Drug: Placebo<br>* Placebo will be injected subcutaneously<br>|
| Experimental: SHR-1905 Dose Level 4<br>SHR-1905 Dose level 4 | Drug: SHR-1905<br>* SHR-1905 will be injected subcutaneously<br>Drug: Placebo<br>* Placebo will be injected subcutaneously<br>|
| Experimental: SHR-1905 Dose Level 5<br>SHR-1905 Dose level 5 | Drug: SHR-1905<br>* SHR-1905 will be injected subcutaneously<br>Drug: Placebo<br>* Placebo will be injected subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence and severity of adverse events | Start of Treatment to end of study (approximately 16 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-1905 administration | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-AUC0-inf | Area under the concentration-time curve from time 0 to infinity after SHR-1905 administration | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-Tmax | Time to Cmax of SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-Cmax | Maximum observed concentration of SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-CL/F | Apparent clearance of SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-Vz/F | Apparent volume of distribution during terminal phase of SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) | 
| Pharmacokinetics-t1/2 | Terminal elimination half-life of SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) | 
| Anti-Drug antibody | The percentage of subjects with positive ADA titers over time for SHR-1905 | Start of Treatment to end of study (approximately 16 weeks) |