A Clinical Study of TQH2929 in Healthy Adult Subjects

Study Overview
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Brief Summary
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This project is divided into a single dose escalation and a multiple dose escalation phase Ia clinical study. This is a single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetic characteristics of TQH2929 injection in healthy adults.

Official Title
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Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Efficacy of TQH2929 in Healthy Adult Subjects

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: TQH2929 injection
* Drug: Placebo injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged between 18 and 55 years old (inclusive), both male and female; The male subject should weigh at least 50 kg, the female subject should weigh at least 45kg. And body mass index (BMI) within 19 26 kg/m2. Good health is defined as having no clinically relevant abnormalities identified by a detailed medical history, clinical signs, vital signs, full physical examination, 12-lead Electrocardiogram (ECG), Chest radiograph, abdominal ultrasound and clinical laboratory tests. Subjects voluntarily joined the study, sign informed consent form before the study and fully understand the study content. Have no pregnancy plan and voluntarily take effective contraception measures from time of screening to at least 6 months after the last dose (subjects and their partners). 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 evaluated the investigator to be not suitable for the trial; People who have abnormal and clinically significant results in vital signs, physical examination, laboratory tests, 12-lead ECG, Chest radiograph and abdominal ultrasound 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) tests; Subjects positive for tuberculoses spot (T-SPOT) result; Clinically significant infection requiring antibiotic or antiviral therapy prior to screening and the entire study period; Had undergone surgery within 4 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 2 months prior to randomization; People who have potential difficulty in blood collection, or have a history of needles or blood sickness； Any clear history of drug or food allergies, particularly those with allergies to similar components to the investigational drugs in this trial; People who have received or are planning to receive inactivated or active vaccines during the 30 days prior to randomization and the entire study period (including the follow-up period); Smoking more than 5 cigarettes per day or using equivalent amounts of nicotine or nicotine-containing products within 6 months prior to randomization, or those who cannot stop using any tobacco-based products during the trial; People who had long-standing alcohol abuse or alcohol consumption of more than 14 units (1 unit = 360 mL of beer or 45 mL of 40% alcohol or 150 mL of wine) of alcohol per week within 3 months prior to screening, or those who cannot refrain from alcohol during the trial, or those 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 biologics within 4 months or 5 half-lives (whichever is longer) prior to randomization; Had taken any prescription drugs, over-the-counter drugs, or herbs within 4 weeks prior to randomization, with the exception of vitamin products; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQH2929 Injection (1 mg/kg)<br>TQH2929 Injection 1 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (3 mg/kg)<br>TQH2929 Injection 3 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (10 mg/kg)<br>TQH2929 Injection 10 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (20 mg/kg)<br>TQH2929 Injection 20 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (30 mg/kg)<br>TQH2929 Injection 30 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (40 mg/kg)<br>TQH2929 Injection 40 mg/kg is administered as a single dose. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Placebo Comparator: Placebo Injection<br>Placebo injection is administered as a single dose or multiple doses (once every two weeks). | Drug: Placebo injection<br>* Placebo comparator<br>|
| Experimental: TQH2929 Injection (900 mg)<br>TQH2929 Injection 900 mg is administered once every two weeks. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (1500 mg)<br>TQH2929 Injection 1500 mg is administered once every two weeks. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|
| Experimental: TQH2929 Injection (1800 mg)<br>TQH2929 Injection 1800 mg is administered once every two weeks. | Drug: TQH2929 injection<br>* TQH2929 injection is a humanized monoclonal antibody that interfering with the signal cascade.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE) rate | The occurrence of all adverse events (AE). | Single administration dose (SAD) group: up to Day 113. Multiple administration dose (SAD) group: up tp Day 141. | 
| Serious adverse events (SAE) rate | The occurrence of all adverse events (SAE). | Single administration dose (SAD) group: up to Day 113. Multiple administration dose (SAD) group: up tp Day 141. | 
| Treatment-related adverse events (TRAE) rate | The occurrence of all treatment-related adverse events (TRAE). | Single administration dose (SAD) group: up to Day 113. Multiple administration dose (SAD) group: up tp Day 141. | 
| Incidence of clinical laboratory abnormalities | Proportion of subjects with clinical laboratory abnormalities | Single administration dose (SAD) group: up to Day 113. Multiple administration dose (SAD) group: up tp Day 141. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach maximum observed serum concentration (Tmax), SAD | Time to reach maximum (peak) serum concentration after administration in SAD group | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Time to reach maximum observed serum concentration (Tmax), multiple administration dose (MAD) | Time to reach maximum (peak) serum concentration after administration in MAD group | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Maximum serum concentration (Cmax), SAD | The maximum observed serum concentration of study drug in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Maximum serum concentration (Cmax), MAD | The maximum observed serum concentration of study drug in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Area under the concentration-time curve from zero to infinity (AUC 0-∞), SAD | Area under the concentration-time curve of the TQH2929 Injection in serum over the time interval from 0 extrapolated to infinity in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Area under the concentration-time curve from zero to infinity (AUC 0-∞), MAD | Area under the concentration-time curve of the TQH2929 Injection in serum over the time interval from 0 extrapolated to infinity in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Area under the concentration-time curve from 0 to last observation (AUC 0-t), SAD | Area under the concentration-time curve of the TQH2929 Injection in serum over the time interval from 0 extrapolated to the last quantifiable data time-point in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Area under the concentration-time curve from 0 to last observation (AUC 0-t), MAD | Area under the concentration-time curve of the TQH2929 Injection in serum over the time interval from 0 extrapolated to the last quantifiable data time-point in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Apparent volume of distribution (Vd/F), SAD | Apparent volume of distribution of the TQH2929 Injection in serum in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Apparent volume of distribution (Vd/F), MAD | Apparent volume of distribution of the TQH2929 Injection in serum in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Apparent clearance (CL/F), SAD | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body, in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Apparent clearance (CL/F), MAD | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body, in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Half-life (t1/2), SAD | The time required for half of the drug to be eliminated from the serum in SAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2353, 2688 hours postdose. | 
| Half-life (t1/2), MAD | The time required for half of the drug to be eliminated from the serum, in MAD group. | 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Time to maximum plasma concentration at steady state (Tmax, ss) | Time to reach the peak plasma concentration at steady state for TQH2929 Injection. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Maximum concentration of drug in plasma at steady state (Cmax, ss) | The peak plasma concentration of TQH2929 Injection during dosing interval at steady state. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Minimum concentration of drug in plasma at steady state (Cmax, ss) | The minimum plasma concentration at steady state. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Average Plasma Concentration at Steady State (Cav,ss) | Cav,ss is the average plasma concentration at steady state. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Area under curve of steady state (AUCss) | Area under the concentration-time curve of TQH2929 at steady state. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Accumulation ratio (Rac) | Rac is a reflection of how much drug is being added to the body relative to how much is being eliminated from the body during a defined period of time. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Degree of fluctuation (DF) | Degree of fluctuation (DF) of repeated using TQH2929 Injection in healthy adults. | MAD group: 1 hour pre-dose, 0, 0.5, 1, 2, 6, 12, 24, 48, 72, 168 hours after injection on Day 1 and Day 29; 1 hour pre-dose on Day 15; 336, 504, 672, 840, 1008, 1344, 1680, 2016, 2352, 2688 hours after dose on Day 29. | 
| Anti-drug antibodies (ADA) | Proportion of subjects with a positive ADA reading at any time point during the study. | SAD group: 1 hour pre-dose, postdose on Day 15, Day 57, Day 85, Day 113. MAD group: 1 hour before the first, second and third dose, post-dose on Day 57, Day 85, Day 113, Day 114. |