Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of the Fully Human Anti-tetanus Toxin Monoclonal Antibody A82 / B86 Injection Combination Formulation

Multicenter, Randomized, Blinded, Controlled Phase I / Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of the Fully Human Anti-tetanus Toxin Monoclonal Antibody A82 / B86 Injection Combination

To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of the full human anti-tetanus toxin monoclonal antibody A82 / B86 injection combination formulation

Study Overview

• Status: Not yet recruiting
• Conditions: Clostridium Tetanus
• Intervention / Treatment: Drug: Human anti-tetanus toxin monoclonal antibody A82 / B86 injection combination preparation; Biological: Adsorbed tetanus vaccine (TT); Drug: Tetanus human immunoglobulin (HTIG); Drug: Whole-human anti-tetanus toxin monoclonal antibody A82 / B86 injection placebo

Detailed Description

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
• Enrollment (Estimated): 190
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jianchang HJC He; Phone Number: China：+86-6363-6790; Email: hejc@yn-cprc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Before the trial, I have a detailed understanding of the nature, significance and possible benefits of the trial, possible inconvenience and potential risks and discomfort, and volunteered to participate in this clinical trial, be able to communicate well with researchers, comply with the requirements of the whole study, and signed a written informed consent;
2. Men or women aged 18~59 (including boundary values) at the time of screening;
3. The weight of female volunteers was 45.0 kg, male volunteers were 50.0 kg, and the body mass index (BMI) was between 18.0 and 27.0 kg / m2 (including the boundary value) (BMI= weight kg / height m2);
4. female volunteers from the 14 days before the first dose to 3 months after the end of the test and voluntary use at least one acceptable contraceptive method, male volunteers from the first time to the trial within 3 months no fertility or donate sperm plan and voluntary use of at least one acceptable contraceptive method.

Exclusion Criteria:

1. People who are known to be allergic to experimental drugs (including excipients and similar drugs), or who suffer from severe allergic diseases or allergies (such as allergic to two or more drugs, food or pollen), may damage the safety of the volunteers by the judgment of the investigator (inquiry);
2. Those with a clear history of allergy to essential substances (such as skin disinfectants and alcohol substances that may be exposed to) during the test (inquiry);
3. tetanus vaccine or tetanus toxin antigen component (DPT vaccine, DPT vaccine, meningitis conjugate vaccine, etc.) vaccinated in the previous 10 years (inquiry);
4. Those who received any live attenuated vaccine or inactivated vaccine (including COVID-19 vaccine) within 1 month (30 days) before the first dose, or received the above vaccine within 3 months after the planned dose (inquiry);
5. Previous history of tetanus infection (inquiry);
6. Known or suspected immune deficiency (inquiry), including immunosuppressive therapy (radiation therapy, chemotherapy, corticosteroid hormones, antimetabolism, cytotoxic drugs) (inquiry, inquiry), HIV infection (inquiry) within 3 months before the first dose (90 days);

7. History of active infection or disease with one of the following conditions:

   Systemic systemic anti-infective therapy within 14 days before the first administration (inquiry, inquiry); Recurrent, chronic, or other active infections, as assessed by the investigator, may increase the volunteer risk (inquiry).

8. Patients with chronic diseases (including hypertension, diabetes, hyperlipidemia, hyperuricemia, etc.) (phase I only); chronic diseases (including hypertension, diabetes, hyperlipidemia, hyperuricemia, etc.) and unstable control (phase II only) (inquiry);
9. People with a history of tuberculosis who are not cured or have active tuberculosis infection during screening (inquiry);
10. has a history of malignancy (active or has been treated but not clearly clinically cured, or may recur during the trial) (inquiry);
11. Patients with a previous history of convulsions, epilepsy, mental or neurological system, or a family history of convulsions or epilepsy (inquiry);
12. Those who have a history of clinically serious disease within 6 months before the first dose (180 days) and are not cured, or those who have acute or chronic diseases that may significantly affect the in vivo process or safety evaluation of the investigational drug (inquiry, inquiry);
13. Those who had received major surgery within 3 months (90 days) prior to the first dose, or who may have significantly affected the process or safety evaluation of the study drug, or who planned to undergo surgery during the study (inquiry, inquiry);
14. Those who have been used or are in significant impact on the in vivo process or safety evaluation of the investigational drug (inquiry, inquiry);
15. Use of other clinical trial drugs / devices within 3 months (90 days) prior to the first dose, or <5 clearance half-lives since the last dose of previous experimental drugs (whichever is older), or participation in other clinical trial planners during the trial (inquiry, inquiry);
16. Drinking more than 28 units of alcohol per week (1 unit =285 ml beer or 25 ml spirits or 40% alcohol) for 3 months (90 days) before the first dose (inquiry);
17. Smoking more than 10 cigarettes or equal amounts of tobacco per day for 1 month (30 days) prior to the first dose (inquiry);
18. Blood loss / blood donation over 400 ml (except female physiologic blood loss) within 3 months (90 days) before the first dose, or receiving blood transfusion or using blood products, or planned to donate during the trial or within 1 month (30 days) after the end of the trial (inquiry);
19. Patients with positive rapid IgG during the screening period (examination);
20. Those with a history of substance abuse (inquiry) or those positive for substance abuse screening during the screening period (examination);
21. Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCV-Ab) antibody, Treponema syphilis antibody (TPPA) or antibody to human immunodeficiency virus (Anti-HIV);
22. Ear temperature during the screening period is> 37.5℃ (examination);
23. Physical examination, vital signs (blood pressure, pulse rate), electrocardiogram, other laboratory tests (laboratory tests not listed separately) or other auxiliary test results during the screening period are judged as abnormal and clinically significant by the study doctor (examination);
24. Women in pregnancy or lactation (inquiry) or those with a positive pregnancy test (examination);
25. Patients with a history of needle acupuncture, blood halo (inquiry), unable to tolerate or without adequate venous access to allow regular venipuncture (inquiry, examination);
26. The volunteers may be unable to cooperate with the study for other reasons or the investigators is not unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Each dose (1.0 ml) contained 1.25 mg of fully human anti-tetanus toxin monoclonal antibody A82 and 1.25 mg of fully human anti-tetanus toxin monoclonal antibody B86,2.5 mg (1.0 ml) / vial	Drug: Human anti-tetanus toxin monoclonal antibody A82 / B86 injection combination preparation; 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.; Biological: Adsorbed tetanus vaccine (TT); containing tetanus toxoid titer not less than 40 IU
Active Comparator: Positive control group; Tetanus with human immunoglobulin	Biological: Adsorbed tetanus vaccine (TT); containing tetanus toxoid titer not less than 40 IU; Drug: Tetanus human immunoglobulin (HTIG); Tetanus human immunoglobulin (HTIG)
Placebo Comparator: Placebo group; There were no active ingredients, and other ingredients were the same	Biological: Adsorbed tetanus vaccine (TT); containing tetanus toxoid titer not less than 40 IU; Drug: Whole-human anti-tetanus toxin monoclonal antibody A82 / B86 injection placebo; There were no active ingredients, and other ingredients were the same

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Twelve months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK evaluation index	Peak Plasma Concentration (Cmax)	Twelve months
PK evaluation index	Area under the plasma concentration versus time curve (AUC)	Twelve months
PK evaluation index	Maximum peak time (Tmax)	Twelve months
PK evaluation index	Half-life period(T1/2)	Twelve months
PK evaluation index	MeanResidenceTime（MRT）	Twelve months
PK evaluation index	Apparent clearance rate (CL / F)	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	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])	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	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).	Twelve months

Collaborators and Investigators

• Sponsor: Changchun BCHT Biotechnology Co.
• Collaborators: The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine; Anning City First People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2024
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Safety; tolerability; pharmacokinetics; immunogenicity; pharmacodynamics; Monoclonal antibody to tetanus
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Infections; Neurologic Manifestations; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Clostridium Infections; Hypocalcemia; Calcium Metabolism Disorders; Tetanus; Tetany; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: B2001-F20220601

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No