To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of the full human anti-tetanus toxin monoclonal antibody A82 / B86 injection combination formulation
Ia (separate administration phase) To evaluate the safety and tolerability of a single intramuscular injection of different doses of CBL8851 injection in healthy adult Chinese volunteers. 1. To evaluate the pharmacokinetic characteristics of a single intramuscular injection of different doses of CBL8851 injection in Chinese healthy adult volunteers; 2. To evaluate the pharmacodynamic characteristics of a single intramuscular injection of different doses of CBL8851 injection in Chinese healthy adult volunteers; 3. To evaluate the immunogenicity characteristics of a single intramuscular injection of different doses of CBL8851 injection in Chinese healthy adult volunteers. Ib (Drug interaction phase) To evaluate the safety and tolerability of intramuscular CBL8851 injection combined with tetanus vaccine in Chinese healthy adult volunteers. 1. To evaluate the pharmacodynamic characteristics of the intramuscular CBL8851 injection combined with the adsorption of tetanus vaccine in Chinese healthy adult volunteers, and to evaluate the drug interaction; 2. To evaluate the pharmacokinetic characteristics of intramuscular CBL8851 injection plus tetanus vaccine in Chinese healthy adult volunteers; 3. To evaluate the immunogenicity characteristics of intramuscular CBL8851 injection combined with tetanus vaccine in Chinese healthy adult volunteers. II designated time Compare the neutralizing antibody activity of intramuscular CBL8851 injection and tetanus human immunoglobulin in Chinese adult volunteers to select the best dose for subsequent efficacy confirmatory tests. 1. to compare the safety of intramuscular CBL8851 injection with tetanus human immunoglobulin in Chinese adult volunteers; 2. To evaluate the immunogenicity characteristics of intramuscular CBL8851 injection in Chinese adult volunteers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
190
Each dose (1.0 ml) contained 1.25 mg of human anti-tetanus toxin monoclonal antibody A82 and 1.25 mg of human anti-tetanus toxin monoclonal antibody B86.
Tetanus human immunoglobulin (HTIG)
There were no active ingredients, and other ingredients were the same
Safety evaluation index
All observed adverse events, serious adverse events, including but not limited to: Clinical indicators Physical examination; vital signs; 12-lead ECG; local reaction; systemic reaction. Laboratory tests: blood routine, urine routine, blood biochemistry (liver function, kidney function, fasting blood glucose, blood lipid, myocardial enzyme spectrum, electrolytes), blood coagulation routine, blood / urine pregnancy test (only fertility women), etc.; Other auxiliary examinations: chest CT and abdominal B-ultrasound.
Time frame: Twelve months
PK evaluation index
Peak Plasma Concentration (Cmax)
Time frame: Twelve months
PK evaluation index
Area under the plasma concentration versus time curve (AUC)
Time frame: Twelve months
PK evaluation index
Maximum peak time (Tmax)
Time frame: Twelve months
PK evaluation index
Half-life period(T1/2)
Time frame: Twelve months
PK evaluation index
MeanResidenceTime(MRT)
Time frame: Twelve months
PK evaluation index
Apparent clearance rate (CL / F)
Time frame: Twelve months
PD evaluation index
The level of neutralizing antibodies against tetanus toxin at 6 h, 12 h, and 24 h, on days 2,3,7,14,21,28,42,56,84, and 105
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containing tetanus toxoid titer not less than 40 IU
Time frame: Twelve months
PD evaluation index
6 h, 12 h, and 24 h at days 2,1,2,3,7,14,21,28,42,56,84, and 105 (0.01 IU / ml \[modified ligand binding assay\] or 0.1 IU / ml \[direct ligand binding assay\])
Time frame: Twelve months
PD evaluation index
Duration of 0.01 IU / ml (modified ligand binding assay) or 0.1 IU / ml (direct ligand binding assay) at days 2,3,7,24,21,56,84 and 24 h after administration
Time frame: Twelve months
Immunogenicity evaluation index
Positive rate of anti-drug antibody (ADA) and neutralizing antibody (Nab) on days 7,14,28,56, and 105 of CBL8851 injection (CBL8851A82 and CBL8851B86).
Time frame: Twelve months