A Clinical Study of BG136 Injection in Healthy Chinese Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a first-in-human, randomized, double-blind, placebo-controlled trial in healthy subjects. The trial consisted of two parts: part 1: single ascending dose (SAD) study and part 2: multiple ascending dose (MAD) study. Each part had multiple Intravenous infusion administration dose groups. Prior to the formal initiation of the dose-escalation trial, the safety, tolerability, and pharmacokinetics (PK) characteristics of a pretest dose (pilot dose) of 2 mg will be evaluated in 2 subjects (both administered BG136 for injection)

Detailed Description
-----------------
This is a first-in-human, randomized, double-blind, placebo-controlled clinical trial in healthy subjects. The trial consists of two parts: Part 1: a single ascending dose (SAD) study with seven dose groups: 2 mg (exploratory dose), 24 mg, 50 mg, 100 mg, 200 mg, and 300 mg, 400 mg (optional dose groups), with two subjects enrolled in the 2 mg group (all receiving the test drug), and eight subjects enrolled in each of the remaining groups (six test drug and two placebo); Part 2: a multiple ascending dose (MAD) study with seven dose groups: two subjects (six test drug and two placebo); and Part III: a randomized, double-blind, placebo-controlled clinical trial in healthy subjects, with a randomized, double-blind, placebo-controlled clinical trial in healthy subjects. Part II: Multiple ascending dose (MAD) study, divided into 3 dose groups: 100 mg, 200 mg and 300 mg, each including 8 healthy subjects (6 test drug, 2 placebo).

Official Title
-----------------
First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single Dose Escalation and Multiple Dose Escalation Phase I Clinical Trial of BG136 for Injection in Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BG136
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese male or female subjects aged 18-55 years (including the threshold); Weight ≥ 50 kg for men and ≥ 45 kg for women and body mass index (BMI): 19.0-26.0 kg/m2 (including borderline values); Subjects understand and comply with the study process, can communicate well with the investigator, volunteer to participate in the trial and sign an informed consent form. Exclusion Criteria: Diseases to be excluded due to clinical abnormalities within 3 months prior to screening, including but not limited to neurological/psychiatric, cardiovascular, hematological and lymphatic, immune, gastrointestinal, urinary, endocrine, metabolic, and skeletal conditions. History of diseases of the urinary, endocrine, respiratory, metabolic and skeletal systems. History of comorbid gastrointestinal related disorders Those who have had surgery within 3 months prior to screening or plan to have surgery during the study period； Screening subjects whose vital signs, physical examination, routine blood, urine, blood biochemistry, coagulation function, and electrocardiogram are judged by the investigator to be abnormal and clinically significant； Subject's imaging determined by the investigator to be clinically significant for abnormalities； Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody screening, human immunodeficiency virus (HIV) antibody screening, treponema pallidum antibody (TP-Ab) any test positive； History of food or drug allergies or other allergic diseases； History of substance abuse in the 12 months prior to screening, or drug use in the 3 months prior to screening, or a positive urine drug screen； Positive breath test results for alcohol or regular alcohol consumption in the 6 months prior to screening, i.e., an average of more than 14 units of alcohol per week (1 unit ≈ 200 mL of beer at 5% alcohol or 25 mL of spirits at 40% alcohol or 85 mL of wine at 12% alcohol), or inability to abstain from alcohol consumption for 48 hours prior to the first dose of the medication and for the entire study period； Smokers who smoked an average of ≥5 cigarettes per day in the 3 months prior to screening or who could not give up smoking 48 hours prior to the first dose and throughout the study period； Those who have received a blood transfusion or used blood products ≥ 400 mL or 2 units within 3 months prior to screening, or those who have lost ≥ 400 mL of blood within 6 months, or those who have donated blood within 3 months； Participated in another clinical trial within 3 months prior to screening and took the trial drug or used the trial device； Any prescription (including vaccines), over-the-counter medications used within 4 weeks prior to screening； Those who have used herbal medicines or health supplements for the treatment and/or prevention of their own disease within 2 weeks prior to screening； Persons with special dietary requirements who are unable to follow a standardized diet or who are unable to avoid xanthine-rich beverages or foods or fruits or fruit juices that may interfere with metabolism for 48 hours prior to dosing and up to study completion; Those who have difficulty in collecting blood from veins or who suffer from needle; Women who are pregnant, breastfeeding, or who have had unprotected sex within 2 weeks prior to screening, or who have had a positive pre-test pregnancy test; Male subjects (or their partners) or female subjects who are planning a pregnancy, sperm donation, or oocyte donation from the time of signing the Informed Consent Form until 3 months after the end of the administration of the medication; Those who do not wish to use one of the medically approved non-pharmacological contraceptives (e.g., intrauterine device or condom) during the trial period; Subjects deemed unsuitable by the investigator to participate in the study.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single-dose and multi-dose, dose escalation, placebo-controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>A single ascending dose (SAD) study divided into 7 dose groups: 2 mg (exploratory dose), 24 mg, 50 mg, 100 mg, 200 mg, and 300 mg, 400 mg (optional dose group), with 2 mg enrolling 2 subjects (all receiving the test drug) and the remaining 8 subjects in each group (6 test drug, 2 placebo). | Drug: BG136<br>* Subjects injected with BG136 in Part 1 and Part 2<br>Drug: Placebo<br>* Subjects injected with Placebo in Part 1 and Part 2<br>|
| Experimental: Part 2<br>Multiple ascending dose (MAD) study, divided into 3 dose groups: 100 mg, 200 mg and 300 mg, each group included 8 healthy subjects (6 test drug, 2 placebo). | Drug: BG136<br>* Subjects injected with BG136 in Part 1 and Part 2<br>Drug: Placebo<br>* Subjects injected with Placebo in Part 1 and Part 2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | up to 14 days | 
| Peak Plasma Concentration (Cmax) | Evaluation of Peak Plasma Concentration (Cmax) | up to 14 days | 
| Area under the plasma concentration versus time curve (AUC)0-t | Evaluation of Area under the plasma concentration versus time curve (AUC)0-t | up to 14 days | 
| Area under the plasma concentration versus time curve (AUC)0-∞ | Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞ | up to 14 days |