The Safety and Tolerability of STSA-1301 Subcutaneous Injection in Healthy Subjects

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, single-ascending dose, phase Ia study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamics, and immunogenicity of STSA-1301 Subcutaneous Injection in healthy subjects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single-ascending Dose, Phase Ia Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamics, and Immunogenicity of STSA-1301 Subcutaneous Injection in Healthy Subjects

Conditions
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Primary Immune Thrombocytopenia

Intervention / Treatment
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* Drug: STSA-1301 subcutaneous injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, male and female, aged between 18 and 65 years, inclusive; Body mass index: 18.0～28.0 kg/m2, inclusive; weight ≥50 kg for males and ≥45kg for females at enrollment; Subjects (including their partners) agree to take highly effective contraceptive measures during the study, and they have no birth plan or sperm donation plan within 3 months after the end of the study; Medical histories, physical examinations, laboratory examinations and study-related examinations and tests of the subjects show normal results or mild abnormalities with no clinical significance before enrollment, and the Investigator judges that they are eligible; Subjects are aware of the risks of the study, and voluntarily participate in the clinical study and sign an informed consent form (ICF). Exclusion Criteria: Pregnant or lactating women; History of cardiovascular, respiratory, kidney, liver, metabolism, endocrine, gastrointestinal, blood, nerve, skin and mental illness, cancer or other major disease that in the judgment of the Investigator might put the subject as risk on this study. After splenectomy or any major surgery within 6 months prior to screening; Subjects have an active infection or have a serious infection (leading to hospitalization or requiring parenteral antibiotic therapy) within 6 weeks prior to the first dose; subjects with clinically active or chronic uncontrolled bacterial, viral or fungal infections at screening; Total IgG was less than the lower limit of normal at screening. Subjects with absolute neutrophil count <1.5X109/L and/or absolute lymphocyte count <1.0X109/L; Subjects have a history of malignancy; Subjects who are allergic to this product or any of its ingredients, history of eczema, asthma or other allergic diseases; Subjects are TIGRA (T cell interferon gamma release assay) positive at screening. If TIGRA is not available, a PPD skin test may be used instead and chest imaging performed at screening showing evidence of latent/active tuberculosis (TB); Positive screening test results for human immunodeficiency virus (HIV) antibodies, syphilis specific antibody, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (Anti-HCV); Presence of electrocardiogram (ECG) abnormalities during the screening period, as defined by an Investigator; Subjects have any conditions affecting blood collection; Subjects whose daily consumption of coffee, tea and/or cola is more than 750 mL in the last 3 months before enrollment; Subject who have nicotine consumption more than 5 cigarettes or the equivalent amount of tobacco per day within 3 months prior to screening; Subjects whose daily consumption of alcohol at the time of screening or at any time within the prior 6 months is more than 2 standard drinks, where 1 standard drink = 360 mL or 12 oz (1 can) of regular-strength (5%) beer; 150 mL or 5 oz wine; 45 mL or 1.5 oz liquor/spirits (40%); abnormal alcohol test results at screening or baseline; History of drug abuse within 1 year prior to screening; subjects with a positive urine drug abuse screen at screening or baseline; Blood loss or donation>400mL within 3 months prior to screening or history of transfusion or use of any blood products within 3 months prior to enrollment; Participation as a subject in any drug or vaccine or medical device clinical trial within 3 months prior to screening; Vaccination or planned vaccination within 4 weeks prior to screening to 3 months after end of dosing; Subjects who have taken drugs that may affect immune function within 6 months before screening, have received any monoclonal antibody or biological agent for treatment within the previous 3 months, and have previous treatment with any prescribed medications, over-the-counter (OTC) medications, herbal medicines or other supplements within 14 days prior to screening; Subjects with any factors that would, in the Investigator's judgment, preclude them from participating in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lowest dose group<br>4 subjects will be randomized to receive lowest dose of STSA-1301 subcutaneous injection or dose-matched placebo (First cohort) | Drug: STSA-1301 subcutaneous injection<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>Drug: Placebo<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>|
| Experimental: low dose group<br>8 subjects will be randomized to receive low dose of STSA-1301 subcutaneous injection or dose-matched placebo (Second cohort) | Drug: STSA-1301 subcutaneous injection<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>Drug: Placebo<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>|
| Experimental: middle dose group<br>8 subjects will be randomized to receive middle dose of STSA-1301 subcutaneous injection or dose-matched placebo (Third cohort) | Drug: STSA-1301 subcutaneous injection<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>Drug: Placebo<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>|
| Experimental: high dose group<br>8 subjects will be randomized to receive high dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fourth cohort) | Drug: STSA-1301 subcutaneous injection<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>Drug: Placebo<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>|
| Experimental: highest dose group<br>8 subjects will be randomized to receive highest dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fifth cohort) | Drug: STSA-1301 subcutaneous injection<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>Drug: Placebo<br>* Subjects will receive the administration dose on Day 0 following protocol requirements.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-related adverse events as assessed by CTCAE 5.0. | To evaluate the safety and tolerability of STSA-1301 subcutaneous injection in healthy adult subjects. | 50 days | 
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests. | Subject incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests (Complete Blood Count (absolute counts and %), Fasting blood glucose concentration, Serum concentrations in Electrolytes, Protein, Albumin, Total Bilirubin, Blood urea nitrogen, Creatinine, Aspartate Aminotransferase, Alanine Aminotransferase, estimated Glomerular Filtration Rate (eGFR), Activated partial thromboplastin time (aPTT), Prothrombin Time test (PT) with International Normalized Ratio (INR) and Urinalysis safety tests (pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase)). | 50 days | 
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in vital signs. | Subject incidence of treatment-emergent clinically significant changes in vital signs (Systolic and Diastolic Blood Pressure in millimeters of mercury (mmHg), Pulse Rate in beats per minute (bpm), Respiratory Rate in beats per minute (bpm) and Body temperature in Celsius). | 50 days | 
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in physical examination. | Subject incidence of treatment-emergent clinically significant changes in physical examination (Skin mucosa, lymph nodes, head and neck, chest, abdomen, musculoskeletal, nervous system). | 50 days | 
| Safety as measured by subject incidence of treatment-emergent clinically significant changes in Electrocardiogram (ECG). | Subject incidence of treatment-emergent clinically significant changes in 12-lead ECGs (Heart Rate in beats per minute (bpm), PR interval in milliseconds (msec), QRS duration in milliseconds (msec), QTc in milliseconds (msec), QT interval in milliseconds (msec)). | 50 days | 
| Maximum plasma concentration (Cmax) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Area under the plasma concentration-time curve from time 0 to the collection time point t of the last measurable concentration (AUC0-t) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Time of maximum concentration (Tmax) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Elimination half-life (t1/2) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Elimination rate constant of plasma drug concentration in terminal phase (λz) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Last measurable concentration (Clast) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Mean residence time (MRT) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Clearance (CL) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 
| Apparent volume of distribution (Vz) | To evaluate the pharmacokinetics (PK) characteristics of STSA-1301 | Pre-dose; after dose 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days and 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in concentration of IgG. | To evaluate the pharmacodynamics (PD) characteristics and immunogenicity of STSA-1301 subcutaneous injection in healthy adult subjects. | Pre-dose; after dose 8 hours, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 14 days, 21 days, 28 days and 49 days | 
| Change from baseline in concentration of anti-drug antibody | To evaluate the pharmacodynamics (PD) characteristics and immunogenicity of STSA-1301 subcutaneous injection in healthy adult subjects. | Pre-dose; after dose 14 days, 28 days, 49 days |