A Randomized, Double-blind, Controlled, Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Intramuscular Injection of Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 68
- 试验地点
- 2
- 主要终点
- The occurrence of adverse events (AEs)/serious adverse events (SAEs) (including injection site reactions) from administration to the last visit
研究概览
简要总结
A Randomized, Double-blind, Controlled, Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Intramuscular Injection of Recombinant Human Anti-tetanus toxin Monoclonal Antibody Injection in Healthy Participants.
详细描述
The primary objective of the study ： evaluate the safety and tolerability of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants. The secondary objectives are:
- to evaluate the pharmacokinetic (PK) characteristics of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants;
- to evaluate the pharmacodynamic (PD) characteristics of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants;
- to evaluate the immunogenicity of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants voluntarily agree to participate in the study and sign the informed consent form (ICF);
- •Aged 18-60 years (inclusive) at the time of ICF signing, regardless of gender, with valid legal identification;
- •Body weight ≥45.0 kg for female participants and ≥50.0 kg for male participants, with a body mass index (BMI) between 18.0 and 28.0 kg/m² (inclusive) (BMI = weight [kg]/height [m²]);
- •Female participants of childbearing potential must have no plans for pregnancy or egg donation during the trial and for 6 months after investigational product administration and must voluntarily use at least one effective contraceptive method. Male participants must have no plans for pregnancy or sperm donation during the trial and for 6 months after investigational product administration, and either the male participant or his female partner of childbearing potential must voluntarily use at least one effective contraceptive method.
排除标准
- •Known allergy to the investigational product (including excipients or similar drugs), or documented hypersensitivity to essential materials used in the trial (e.g., skin disinfectants); or history of severe allergic diseases, hypersensitivity to monoclonal antibodies, or allergic constitution deemed by investigators to compromise participant safety;
- •Acute/chronic medical conditions that may significantly affect drug metabolism or safety assessments per investigator judgment;
- •History of autoimmune diseases or immunodeficiency disorders (including HIV-positive screening);
- •Chronic hepatitis B/C (HBsAg or HCV antibody-positive during screening);
- •History/family history of seizures, epilepsy, or neuropsychiatric disorders;
- •Major surgery within 3 months (90 days) prior to dosing, or planned surgery during the trial;
- •Prior tetanus infection or use of passive tetanus immunoglobulins within 6 months (180 days) before dosing;
- •Tetanus-toxoid-containing vaccination (e.g., DTaP, Td, meningococcal conjugate vaccines) within 10 years;
- •Positive tetanus IgG rapid test during screening;
- •Receipt of live/inactivated vaccines within 1 month (30 days) before dosing or planned vaccination during the trial;
- •Systemic corticosteroids/immunosuppressants within 3 months (90 days) (excluding inhaled/topical use);
- •Prescription/OTC/herbal medications within 14 days or <5 half-lives (whichever is longer) prior to dosing, particularly those interfering with the investigational monoclonal antibody's PK/safety (per criterion #11 for exceptions);
- •Participation in other clinical trials involving investigational drugs/devices within 3 months (90 days) or planned concurrent enrollment;
- •Excessive alcohol intake (>14 units/week; 1 unit = 360 mL beer/45 mL 40% liquor/150 mL wine), alcohol use within 48 hours pre-dose, or positive breathalyzer test;
- •Heavy smoking (>10 cigarettes/day or equivalent) within 1 month (30 days);
- •Blood loss/donation >400 mL within 3 months (90 days) or planned donation/transfusion during the trial;
- •Inability to avoid strenuous exercise within 14 days post-dosing;
- •Substance abuse history or positive drug screening;
- •Positive syphilis antibody test during screening;
- •Clinically significant abnormalities in screening assessments (e.g., ALT >1.5×ULN, creatinine >ULN, neutrophils <1.5×10⁹/L, platelets <100×10⁹/L, hemoglobin <100 g/L);
- •Pregnant/lactating women or positive pregnancy test;
- •Needle phobia, poor venous access, or intolerance to venipuncture;
- •Any other condition deemed by investigators to preclude compliance or safe participation.
研究组 & 干预措施
Group 1 (0.2 mg dose group)
A single dose was administered to 3 enrolled participants, who were randomized in a 2:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period and were evaluated as safe and tolerable, administration for the next dose group could proceed.
干预措施: Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection (Drug)
Group 1 (0.2 mg dose group)
A single dose was administered to 3 enrolled participants, who were randomized in a 2:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period and were evaluated as safe and tolerable, administration for the next dose group could proceed.
干预措施: Placebo (Drug)
Group 2 (2 mg dose group)
A single dose was administered to 8 enrolled participants, who were randomized in a 3:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the trial proceeded to the next dose group.
干预措施: Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection (Drug)
Group 2 (2 mg dose group)
A single dose was administered to 8 enrolled participants, who were randomized in a 3:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the trial proceeded to the next dose group.
干预措施: Placebo (Drug)
Group 3 (5 mg dose group)
A single dose was administered to 15 enrolled participants, who were randomized in a 4:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the study proceeded to the next cohort.
干预措施: Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection (Drug)
Group 3 (5 mg dose group)
A single dose was administered to 15 enrolled participants, who were randomized in a 4:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo. After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the study proceeded to the next cohort.
干预措施: Placebo (Drug)
Group 4 (10 mg dose group)
A single dose was administered to 27 enrolled participants, who were randomized in a 4:4:1 ratio to receive either:
the recombinant human anti-tetanus toxin monoclonal antibody injection,
human tetanus immunoglobulin (HTIG) injection, or
placebo.
After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the study advanced to the next phase.
干预措施: Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection (Drug)
Group 4 (10 mg dose group)
A single dose was administered to 27 enrolled participants, who were randomized in a 4:4:1 ratio to receive either:
the recombinant human anti-tetanus toxin monoclonal antibody injection,
human tetanus immunoglobulin (HTIG) injection, or
placebo.
After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the study advanced to the next phase.
干预措施: Human Tetanus Immunoglobulin (Drug)
Group 4 (10 mg dose group)
A single dose was administered to 27 enrolled participants, who were randomized in a 4:4:1 ratio to receive either:
the recombinant human anti-tetanus toxin monoclonal antibody injection,
human tetanus immunoglobulin (HTIG) injection, or
placebo.
After all participants completed the 14-day safety observation period for the current dose group and were evaluated as safe and tolerable, the study advanced to the next phase.
干预措施: Placebo (Drug)
Group 5 (15 mg dose group)
A single dose was administered to 15 enrolled participants who were randomized in a 4:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo.
As this represented the highest planned dose level, the sponsor and investigators jointly determined whether to continue dose escalation based on the absence of tolerability concerns.
干预措施: Recombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection (Drug)
Group 5 (15 mg dose group)
A single dose was administered to 15 enrolled participants who were randomized in a 4:1 ratio to receive either the recombinant human anti-tetanus toxin monoclonal antibody injection or placebo.
As this represented the highest planned dose level, the sponsor and investigators jointly determined whether to continue dose escalation based on the absence of tolerability concerns.
干预措施: Placebo (Drug)
结局指标
主要结局
The occurrence of adverse events (AEs)/serious adverse events (SAEs) (including injection site reactions) from administration to the last visit
时间窗: 105 days
Types of Adverse Events / Serious Adverse Reactions
The occurrence of adverse events (AEs)/serious adverse events (SAEs) (including injection site reactions) from administration to the last visit
时间窗: 105Days
Relationship of Adverse Events (AEs)/Serious Adverse Reactions (SARs) to the Investigational Product
The clinical significance of changes in observation indicators at different time points after drug injection compared to pre-administration.
时间窗: 105Days
12-lead electrocardiogram examination：ST Segment
Clinically significant changes in laboratory parameters from baseline at specified timepoints post-dosing
时间窗: 105Days
Complete Blood Count (CBC)
次要结局
- Pharmacodynamic Endpoints(0 to 12 hours)
- Pharmacokinetic Endpoints(105Days)
- Pharmacodynamic Endpoints(105Days)
- Immunogenicity Endpoints(105Days)
- Exposure-Response Analysis, E-R Analysis(105Days)