Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Healthy Adults

Trinomab

Status and phase: Completed; Phase 1

Conditions: Healthy Adult Subjects

Treatments: Biological: TNM002 Dosage 1 (10 μg/kg); Biological: Placebo; Biological: TNM002 Dosage 3 (100 μg/kg); Biological: TNM002 Dosage 2 (35 μg/kg); Biological: TNM002 Dosage 4 (250 μg/kg)

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04629131

TNM002-P1-AU01

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics properties of TNM002 following a single intramuscular dose in healthy adult subjects.

Full description

The study a randomized, double-blinded, placebo-controlled, dose-escalation phase I trial. A total of 32 healthy adult subjects will be enrolled into 4 cohorts sequentially. Each participant will receive a single IM dose of TNM002 or placebo according to the cohort in which they were enrolled. After injection (Day 1), participants remain in the study site for observation up to 5 days. Following completion of the safety assessments and sampling for PK/PD analyses on Day 4, participants will be discharged from the study site. On Day 8, 15, 29, 43, 64 and 85, participants will return for safety assessments.

Enrollment: 32 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Each subject must meet the following criteria to be enrolled in this study:

1. Healthy male or female, 18-55 years of age (both inclusive);

2. Able to give signed written informed consent form;

3. Able to well communicate with investigators as well as understand and adhere to the requirements of this study.

4. Body mass index (BMI, weight [kg]/height [m]2) within 18.0-32.0 kg/m2 (both inclusive);

5. Blood Pressure (BP) and 12-lead ECG showing no clinically significant abnormalities at the discretion of the Principal Investigator during screening;

6. Subjects having no clinically significant abnormality on physical examination, clinical laboratory tests, liver function or kidney function as determined by Principal Investigator (PI);

7. Females must be either under surgical sterile (i.e. had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months before the first dose of study drug) or under postmenopausal for at least 1 year before the first dose of study drug or agree to use an acceptable method of contraception from screening until 90 days after last study drug administration. Males who are sexually active and who are partners of women of childbearing potential must agree to use effective contraception from screening until 90 days after last drug administration.

   • acceptable method of contraception

     • Use of intrauterine device
     • Use of oral, injected or implanted hormonal methods of contraception
     • Concomitant use of barrier contraception method
     • Surgical contraception methods (e.g., vasectomy, salpingectomy, hysterectomy, etc.)

Exclusion criteria

Subjects who meet any of the following criteria will be excluded from the study:

1. History or evidence of severe drug or excipient allergy, or hypersensitivity to other therapeutic mAbs;
2. History or evidence of autoimmune disease or possible immunodeficiency state, including positive screening test for HIV;
3. History or evidence of chronic hepatitis, including positive screening test for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody;
4. History or evidence of tetanus infection, or exposure to tetanus vaccine within 6 months prior to the fist drug administration;
5. Exposure to any live attenuated vaccine within 4 weeks prior to the fist drug administration;
6. Exposure to any inactivated vaccine within 2 weeks prior to the fist drug administration;
7. History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may have interfered with the evaluation of the safety or immunogenicity of the drug or compromised the safety of the subject; for example, a clinically relevant history of respiratory, thyroid, gastrointestinal, renal, hepatic, hematological, lymphatic, oncologic, cardiovascular, psychiatric, neurological, musculoskeletal, genitourinary, infective, inflammatory, immunological, dermatological, or connective tissue disease
8. Subjects with surgery (except for minor outpatient surgery) within past 3 months prior to screening, or planned surgery during study;
9. Subjects with intolerance or insufficient venous access to permit regular venepuncture;
10. Known or suspected history of drug abuse within the past 5 years or with positive urine drug test at the screening;
11. Donated blood >400 mL or significant blood loss equivalent to 400 mL or received blood transfusion within 3months of screening; or donated blood >200 mL or significant blood loss equivalent to 200 mL within 1 month prior to the screening;
12. Participation in any other clinical studies with chemical or biological drugs or device within 4 weeks or 5 times the half-life of the specific drug/biologics (whichever is longer), prior to the first drug administration;
13. Use of any other drug, including over-the-counter medications, herb medicines within 14 days prior to the first drug administration (except for contraceptive medication in WOCBP, or concomitant medications that are considered necessary for the subject's welfare and unlikely to interfere with the study);
14. Receipt of an Ig or blood product within 90 days prior to the first drug administration;
15. Receipt of immunosuppressive medications, other than inhaled or topical immunosuppressant drugs, within 45 days prior to the first drug administration;
16. Habitual use of nicotine products or smoking within 3 months (more than 5 cigarettes per day) prior to screening or unwilling to refrain from nicotine products during study participation;
17. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week (1 Unit=360 mL of beer or 45 mL of alcohol 40% or 150 mL of wine) or taking a product containing alcohol 2 days prior to dosing, or having a positive alcohol breath test during the screen period.;
18. Malignancy within 5 years of screening visit (except basal cell skin carcinoma);
19. Subject who is considered unsuitable for participating in the study in the opinion of investigator;
20. Nursing mothers or pregnant women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 4 patient groups

Cohort 1 TNM002 10 μg/kg/Placebo

Experimental group

Description:

Sentinel dosing will be conducted for Cohort 1. Two participants will be dosed (1 with TNM002, 1 with placebo) at least 72 hours prior to subsequent dosing. The remaining participants will only be dosed if no significant safety signals are identified in the sentinel participants. In total, eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).

Treatment:

Biological: Placebo

Biological: Placebo

Biological: Placebo

Biological: TNM002 Dosage 1 (10 μg/kg)

Biological: Placebo

Cohort 2 TNM002 35 μg/kg/Placebo

Experimental group

Description:

Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).

Treatment:

Biological: Placebo

Biological: Placebo

Biological: Placebo

Biological: TNM002 Dosage 2 (35 μg/kg)

Biological: Placebo

Cohort 3 TNM002 100 μg/kg/Placebo

Experimental group

Description:

Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).

Treatment:

Biological: Placebo

Biological: Placebo

Biological: Placebo

Biological: TNM002 Dosage 3 (100 μg/kg)

Biological: Placebo

Cohort 4 TNM002 250 μg/kg/Placebo

Experimental group

Description:

Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).

Treatment:

Biological: TNM002 Dosage 4 (250 μg/kg)

Biological: Placebo

Biological: Placebo

Biological: Placebo

Biological: Placebo