A Clinical Trial of TQC2938 Injection in Healthy Adult Subjects

Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.84 enrolled

Overview

The study is designed in two phases: single-dose administration and multiple-dose administration. A randomized, double-blind, placebo-controlled trial design was used to evaluate the safety, tolerability, pharmacokinetic characteristics and immunogenicity of TQC2938 injection in healthy adults.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Asthma

Interventions

TQC2938 InjectionDRUG

TQC2938 injection is a humanized monoclonal antibody that interfering with the signal cascade.

TQC2938 PlaceboDRUG

TQC2938 Placebo is a placebo comparator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Sign informed consent before the study to fully understand the purpose, process and possible adverse reactions of the test. * Adults aged between 18 and 60 years (inclusive)，both male and female; * The male subject should weigh at least 50kg, the female subject should weigh at least 45kg. And body mass index (BMI) within 18\~28 kg/m2 (inclusive); * The subjects were able to communicate well with the investigators, voluntarily and were able to understand and follow the protocol to complete the study; * Female patient had no plans to become pregnant for 6 months from the date of signing the informed consent to the last dose, and must use effective non-drug contraception with their sexual partners of childbearing age。 Exclusion Criteria: * Pregnant or lactating women; * Past medical history or current cardiac, endocrine, metabolic, renal, hepatic, gastrointestinal, skin, infection, hematological, neurological or psychiatric diseases/abnormalities, or related chronic abnormalities, or related chronic diseases, or acute diseases, and the investigator evaluated that the subject was not suitable for the trial; * People who have abnormal and clinically significant results in vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG) and Chest radiograph during screening period; * Subjects Positive for Any of Hepatitis B Virus Surface Antigen (HBsAg), Hepatitis C Virus Antibody (Anti-HCV), Human Immunodeficiency Virus Antibody (Anti-HIV), and Treponema Pallidum Antibody (Anti-TP); * A history of clinically significant infections, including upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI), occurred within 30 days prior to and during screening and required antibiotic or antiviral treatment; * Had undergone surgery within 8 weeks prior to screening period or expected to undergo surgery during the study period; * Participated in any clinical trial within 3 months prior to the screening period; * Received immunoglobulins or blood products within 30 days prior to randomization; * Blood donation or significant blood loss of more than 400 mL within 3 months prior to randomization, or plan to donate blood within 3 months; * Potential blood collection difficulties, can not tolerate venipuncture or have a history of fainting needles and fainting blood; * A history of allergic reaction to treatment with another therapeutic monoclonal antibody or biologics, a history of any well-defined drug or food allergy, especially to ingredients similar to the drug in this trial; * Those who received or planned to receive inactivated or active vaccines within 30 days prior to randomization or throughout the study period, including the follow-up period； * Those who smoked more than 5 cigarettes/day or used a comparable amount of nicotine or nicotine-containing products in the 6 months prior to randomization, or could not stop using any tobacco products during the trial period； * People with chronic alcohol abuse or who drank more than 14 units of alcohol per week in the 3 months prior to screening (1 unit =360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine), or who could not abstain during the test period, or who tested positive for alcohol breath； * History of drug abuse or a positive result of urine drug test at screening; * Received any marketed or investigational biological agent (other than vaccines) within 4 months or 5 half-lives (whichever is older) prior to randomization； * Any prescription, over-the-counter, and herbal medicines, except vitamin products, were taken in the 4 weeks prior to randomization； * Use of any systemic cytotoxicity or systemic immunosuppressants within 6 months prior to randomization or during the study period, or any local cytotoxin or local immunosuppressive drug within 30 days or 5 half-life periods (whichever is longer) prior to randomization or during the study period； * Any situation in which the investigator believes that this poses a safety risk to the subject in the trial or may interfere with the conduct of the study, or that the investigator believes that the subject may not be able to complete the study or may not be able to comply with the requirements of the study.

Locations (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Outcomes

Primary Outcomes

Adverse events (AEs)

The occurrence of all adverse events (AEs).

Time frame: Single dose: Up to Day 113. Multiple doses: Up to Day 169

Serious adverse events (SAEs)

The occurrence and incidence of all serious adverse events (SAEs).

Time frame: Single dose: Up to Day 113. Multiple doses: Up to Day 169

Clinical laboratory abnormalities

Incidence of abnormal clinical laboratory examination, vital signs, physical examination, 12-lead electrocardiogram, etc.

Time frame: Single dose: Up to Day 113. Multiple doses: Up to Day 169

Secondary Outcomes

Maximum serum concentration (Cmax) of subcutaneous injection for single dose

The Cmax is the maximum observed serum concentration of study drug.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Maximum serum concentration (Cmax) of intravenous injection for single dose

The Cmax is the maximum observed serum concentration of study drug.

Time frame: Single dose: pre-dose (-1 to 0 hour), 0.5hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Maximum serum concentration (Cmax) of subcutaneous injection for multiple doses

The Cmax is the maximum observed serum concentration of study drug.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of days 1, 29, 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose on multiple dose of days 1 and 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Data from ClinicalTrials.gov

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Time to reach maximum observed serum concentration (Tmax) of subcutaneous injection for single dose

Time to reach maximum (peak) serum concentration following drug administration.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Time to reach maximum observed serum concentration (Tmax) of intravenous injection for single dose

Time to reach maximum (peak) serum concentration following drug administration.

Time frame: Single dose: pre-dose (-1 to 0hour), 0.5hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Time to reach maximum observed serum concentration (Tmax) of subcutaneous injection for multiple doses

Time to reach maximum (peak) serum concentration following drug administration.

Time frame: Multiple doses: pre-dose (-1 to 0hour) of days 1, 29, 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504hours post-dose of days 1 and 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Minimum concentration of drug in serum at steady state (Cmin, ss) of subcutaneous injection for multiple doses

Cmin,ss is the minimum serum concentration at steady state.

Time frame: Multiple doses: Pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Area under the concentration-time curve from 0 to last observation (AUC [0-t]) of subcutaneous injection for single dose

Area under the concentration-time curve of the TQC2938 Injection in serum over the time interval from 0 extrapolated to the last quantifiable data point.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Area under the concentration-time curve from 0 to last observation (AUC [0-t]) of intravenous injection for single dose

Area under the concentration-time curve of the TQC2938 Injection in serum over the time interval from 0 extrapolated to the last quantifiable data point.

Time frame: Single dose: pre-dose (-1 to 0 hour), 0.5 hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Area under the concentration-time curve from 0 to last observation (AUC [0-t]) of of subcutaneous injection for multiple dose

Area under the concentration-time curve of the TQC2938 Injection in serum over the time interval from 0 extrapolated to the last quantifiable data point.

Time frame: Multiple doses: pre-dose(-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Maximum concentration of drug in serum at steady state (Cmax, ss) of subcutaneous injection for multiple doses

Cmax, ss is the peak serum concentration of TQC2938 Injection during dosing interval at steady state.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Time to maximum serum concentration at steady state (Tmax, ss) of subcutaneous injection

Tmax,ss is defined as time to reach the peak serum concentration at steady state for TQC2938 Injection.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Area under curve of steady state (AUCss) of subcutaneous injection

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of TQC2938 Injection in serum.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Half-life (t1/2) of subcutaneous injection for single dose

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Half-life (t1/2) of intravenous injection for single dose

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.

Time frame: Single dose: pre-dose (-1 to 0 hour), 0.5 hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Half-life (t1/2) of intravenous injection for multiple dose

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Apparent volume of distribution (Vd/F) of subcutaneous injection for single dose

Apparent volume of distribution of the TQC2938 Injection in serum.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Apparent volume of distribution (Vd/F) of intravenous injection for single dose

Apparent volume of distribution of the TQC2938 Injection in serum.

Time frame: Single dose: pre-dose (-1 to 0 hour), 0.5 hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Apparent volume of distribution (Vd/F) of subcutaneous injection for multiple dose

Apparent volume of distribution of the TQC2938 Injection in serum.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Apparent clearance (CL/F) of subcutaneous injection for single dose

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: Single dose: pre-dose (-1 to 0 hour),1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352 and 2688 hours post-dose

Apparent clearance (CL/F) of intravenous injection for single dose

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: Single dose: pre-dose (-1 to 0 hour), 0.5 hours after the start of administration, and 0,0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504, 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose

Apparent clearance (CL/F) of subcutaneous injection for multiple dose

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Accumulation ratio (Rac) of subcutaneous injection for multiple dose

To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of TQC2938 Injection in serum.

Time frame: Multiple doses: pre-dose (-1 to 0 hour) of day 1, day 29, day 57, and 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 264, 336, 504 hours post-dose of day 1 and day 57, and 672, 1008, 1344, 1680, 2016, 2352, 2688 hours post-dose of day 57

Anti-drug antibodies (ADA)

Incidence of ADA, a participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.

Time frame: Single dose: (-1 to 0 hour) (pre-dose), 672, 1344, 2016 and 2688 hours postdose. Multiple doses: (-1 to 0 hour) before the first,second and third administration, 1344 and 2688 hours after intravenous injection of Day 57