A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PB-718 Injection in Chinese Obese Subjects.

Study Overview
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Brief Summary
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The trial is conducted in a single-center, randomized, double-blind, placebo-controlled, dose-increasing design. To evaluate the safety, tolerability, PK characteristics, efficacy and immunogenicity of PB-718 injection in Chinese obese subjects.

Detailed Description
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The trial is conducted in a single-center, randomized, double-blind, placebo-controlled, dose-increasing design. To evaluate the safety, tolerability, PK characteristics, efficacy and immunogenicity of PB-718 injection in Chinese obese subjects. The study consists of three dose groups, each of which is planned to include 12 subjects (9 receiving the study drug and 3 receiving placebo), for a total of 36 patients. Subjects will receive 12 weeks of treatment after screening and complete 8 weeks of safety follow-up.

Official Title
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A Phase Ib_IIa, Single-center, Randomized, Double-blind, Placebo-controlled, Multiple Dose Escalating Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PB-718 Injection in Chinese Obese Subjects.

Conditions
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Obesity

Intervention / Treatment
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* Drug: PB-718
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese male or female subjects aged 18-60 years (both inclusive). Body weight ≥70 kg(male) or 60 kg(femle), and body mass index (BMI) ≥28.0 kg/m2 at screening. Weight change <5% in the past 3 months before screening. Exclusion Criteria: FPG ≥7.0mmol/L or glycosylated hemoglobin (HbA1c) ≥6.5% or diagnosed diabetes FPG <3.9 mmol/L at screening and/or a history of hypoglycemia. History of Cushing's syndrome, polycystic ovaries, or other hereditary endocrine disorders, or obesity caused by secondary factors such as cortisol hormones. Abnormal TSH, FT3, FT4 or diagnosed thyroid dysfunction History of multiple endocrine neoplasia syndrome type 2 (MEN-2) or medullary thyroid carcinoma (MTC). Diagnosed cardiovascular and cerebrovascular diseases with obvious clinical significance within 6 months before screening Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at screening or randomization. PR intervals > 210 msec and/or QRS > 120 msec and/or QTcF > 450 msec at screening or randomization. Serum amylase or lipase > 3× upper limit of normal (ULN) at screening or before randomization, or previously diagnosed acute/chronic pancreatitis. Low density lipoprotein cholesterol(LDL-C) ≥4.40 mmol/L or triglyceride (TG) ≥5.65 mmol/L. Use of any approved or unapproved drugs or products that have an effect on body weight within 3 months prior to screening History of bariatric surgery for weight loss 1 year before screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PB-718<br>Low dose level of PB-718 administered on the first day of week 1-12 according to the dose-escalation design Medium dose level of PB-718 administered on the first day of week 1-12 according to the dose-escalation design High dose level of PB-718 administered on the first day of week 1-12 according to the dose-escalation design | Drug: PB-718<br>* Administered subcutaneously once a week<br>|
| Placebo Comparator: Placebo<br>Matched placebo administered on the first day of week 1-12 according to the dose-escalation design | Drug: Placebo<br>* Administered subcutaneously once a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events |  | From the first dosing (Day 1 ) of study drug until completion of the post treatment follow-up visit (20 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile | Cmax | From the first dose (Day 1 ) of study drug until 12 week | 
| Pharmacokinetic profile | Tmax | From the first dose (Day 1 ) of study drug until 12 week | 
| Pharmacokinetic profile | AUC0-tau | From the first dose (Day 1 ) of study drug until 12 week | 
| Pharmacokinetic profile | AUC0-last | From the first dose (Day 1 ) of study drug until 12 week | 
| Pharmacokinetic profile | t1/2 | From the first dose (Day 1 ) of study drug until 12 week | 
| Proportion of participants with ≥5% weight loss |  | week 12 | 
| Change in body weight from baseline |  | Week12 | 
| Change in FPG from baseline |  | week 12 |