A Study to Evaluate the Safety, Tolerability and Pharmacokinetics Pharmacodynamics of SHR-2010 by Intravenously/Subcutaneously in Healthy Subject

Study Overview
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Brief Summary
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The study is being conducted to Evaluate the Safety, Tolerability and Pharmacokinetics pharmacodynamics of SHR-2010 by intravenously/subcutaneously in Healthy Subject.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous/Subcutaneous Injection of SHR-2010 in Healthy Subjects: a Randomized, Double-blind, Dose-increasing, Placebo-controlled Phase I Clinical Trial

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: SHR-2010 injection
* Drug: SHR-2010 injection placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide a written informed consent. Male or non-pregnant, non-lactating female ages 18 to 55 years old. Weight ≥ 45 kg, and body mass index (BMI) must range from 18 to 28 kg/m2 . Healthy subjects as determined by absence of clinically significant abnormalities on medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory tests performed at screening or baseline period. Subjects must be willing to use a highly effective method of contraception as deemed appropriate by the investigator throughout the study and for at least 3 months after the last study drug administration. Exclusion Criteria: Evidence or history of serious cardiovascular, hepatic, renal, gastrointestinal, psychiatric, neurological, haematological, or metabolic diseases within 5 years. Subjects with tuberculosis diagnosed by Interferon Gamma Release Assays (IGRA) or chest X-ray. Subjects had any surgery within the past 6 months before screening or planned to undergo surgery during the study period. Estimated Glomerular Filtration Rate（eGFR）<90 mL/min/1.73m2. Positive for hepatitis (including hepatitis B and C), HIV or syphilis at screening. Systolic blood pressure (SBP) > 140 mm Hg or < 90 mm Hg, or diastolic blood pressure (DBP) > 90 mm Hg or < 60 mm Hg and has been considered clinically significant. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyl transferase (GGT) ≥2.0 x ULN, or total bilirubin ≥1.5 x ULN. Clinically significant abnormal 12-lead ECG at screening (male with QTcF > 450 ms or female with QTcF > 470 ms). Female subjects who had unprotected sexual behaviour within 14 days before screening. Positive for alcohol breath test at screening or baseline period. Positive urinary drug test at screening or baseline period. Blood collection is difficult or cannot tolerate venipuncture blood collection. Allergic to any ingredient or component in the study drug. Subjects who have taken any prescription drugs, over-the-counter drugs, or Chinese herbal medicine within 14 days prior to using the study drug. Subjects who smoked more than 5 cigarettes daily in the 1 month before screening. History of regular alcohol consumption exceeding 3 units/day for women or 5 units/day for men, more than twice per week (1 unit = 150 ml of beer or 50 ml of wine or 17 ml of alcoholic spirits) within 3 months before screening. Participated in any other clinical trials of any drug or medical device within 3 months before screening. Donated blood or blood products or had substantial loss of blood (more than 400 mL) within 1 month before screening, or received any blood or blood products within 2 months prior to screening. Subjects who received live (attenuated) vaccine within 1 month prior to screening or consider getting a vaccination during the study. The employee of investigator or study centre, with direct involvement in the proposed study. The investigators determined that other conditions were inappropriate for participation in this clinical trial.

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
Interventional Model Description: SHR-2010 injection compared with placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment for intravenously/subcutaneously<br>Treatment for intravenously: 6 dose groups； Treatment for subcutaneously: 3 dose groups. | Drug: SHR-2010 injection<br>* Treatment for intravenously: 6 subjects for SR-2010 injection. Treatment for subcutaneously: 8 subjects for SR-2010 injection.<br>|
| Placebo Comparator: Placebo for intravenously/subcutaneously<br>Treatment for intravenously: 6 dose groups； Treatment for subcutaneously: 3 dose groups. | Drug: SHR-2010 injection placebo<br>* Treatment for intravenously: 2 subjects for placebo. Treatment for subcutaneously: 2 subjects for placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: Incidence of subjects with adverse events (AEs) | Incidence of AEs, including any abnormal findings in vital signs, and/or physical examination and/or clinical laboratory assessments and/or 12-lead ECG evaluation and/or IGRA. | Baseline up to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter: AUC0-t for SHR-2010 | AUC0-t: Area under the plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: AUC0-∞ for SHR-2010 | AUC0-∞: Area under the plasma concentration-time curve from time zero extrapolated to infinity | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: Cmax for SHR-2010 | Cmax: Maximum plasma concentration | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: Tmax for SHR-2010 | Tmax: Time to reach maximum plasma concentration | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: t1/2 for SHR-2010 | t1/2: Terminal half-life | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: CL of SHR-2010 for administration intravenously | CL: Clearance | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: CL/F of SHR-2010 for administration subcutaneously | CL/F: Apparent clearance | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: V of SHR-2010 for administration intravenously | V: Volume of distribution | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: V/F of SHR-2010 for administration subcutaneously | V/F: Apparent volume of distribution | Baseline up to Day 85 | 
| Pharmacokinetics (PK) parameter: Bioavailability (F) of SHR-2010 | Bioavailability of SHR-2010 for administration subcutaneously. | Baseline up to Day 85 | 
| Pharmacodynamics (PD): C4b level in the serum | C4b level in the serum. | Baseline up to Day 85 | 
| Immunogenicity: Proportion of anti-drug antibodies (ADA) positive subjects | Proportion of anti-drug antibodies (ADA) positive subjects. | Baseline up to Day 85 |