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
Overview
- Phase
- Phase 1
- Intervention
- STSA-1301 subcutaneous injection
- Conditions
- Primary Immune Thrombocytopenia
- Sponsor
- Staidson (Beijing) Biopharmaceuticals Co., Ltd
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Mean residence time (MRT)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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;
Arms & Interventions
lowest dose group
4 subjects will be randomized to receive lowest dose of STSA-1301 subcutaneous injection or dose-matched placebo (First cohort)
Intervention: STSA-1301 subcutaneous injection
lowest dose group
4 subjects will be randomized to receive lowest dose of STSA-1301 subcutaneous injection or dose-matched placebo (First cohort)
Intervention: Placebo
low dose group
8 subjects will be randomized to receive low dose of STSA-1301 subcutaneous injection or dose-matched placebo (Second cohort)
Intervention: STSA-1301 subcutaneous injection
low dose group
8 subjects will be randomized to receive low dose of STSA-1301 subcutaneous injection or dose-matched placebo (Second cohort)
Intervention: Placebo
middle dose group
8 subjects will be randomized to receive middle dose of STSA-1301 subcutaneous injection or dose-matched placebo (Third cohort)
Intervention: STSA-1301 subcutaneous injection
middle dose group
8 subjects will be randomized to receive middle dose of STSA-1301 subcutaneous injection or dose-matched placebo (Third cohort)
Intervention: Placebo
high dose group
8 subjects will be randomized to receive high dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fourth cohort)
Intervention: STSA-1301 subcutaneous injection
high dose group
8 subjects will be randomized to receive high dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fourth cohort)
Intervention: Placebo
highest dose group
8 subjects will be randomized to receive highest dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fifth cohort)
Intervention: STSA-1301 subcutaneous injection
highest dose group
8 subjects will be randomized to receive highest dose of STSA-1301 subcutaneous injection or dose-matched placebo (Fifth cohort)
Intervention: Placebo
Outcomes
Primary Outcomes
Mean residence time (MRT)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Time of maximum concentration (Tmax)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Safety as measured by subject incidence of treatment-emergent clinically significant changes in vital signs.
Time Frame: 50 days
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).
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Elimination half-life (t1/2)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Elimination rate constant of plasma drug concentration in terminal phase (λz)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Last measurable concentration (Clast)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Number of treatment-related adverse events as assessed by CTCAE 5.0.
Time Frame: 50 days
To evaluate the safety and tolerability of STSA-1301 subcutaneous injection in healthy adult subjects.
Safety as measured by subject incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests.
Time Frame: 50 days
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)).
Safety as measured by subject incidence of treatment-emergent clinically significant changes in physical examination.
Time Frame: 50 days
Subject incidence of treatment-emergent clinically significant changes in physical examination (Skin mucosa, lymph nodes, head and neck, chest, abdomen, musculoskeletal, nervous system).
Safety as measured by subject incidence of treatment-emergent clinically significant changes in Electrocardiogram (ECG).
Time Frame: 50 days
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)).
Maximum plasma concentration (Cmax)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Area under the plasma concentration-time curve from time 0 to the collection time point t of the last measurable concentration (AUC0-t)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Clearance (CL)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Apparent volume of distribution (Vz)
Time Frame: 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
To evaluate the pharmacokinetics (PK) characteristics of STSA-1301
Secondary Outcomes
- Change from baseline in concentration of anti-drug antibody(Pre-dose; after dose 14 days, 28 days, 49 days)
- Change from baseline in concentration of IgG.(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)