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

Phase 1

Completed

• Conditions: Obesity
• Interventions: Drug: PB-718; Drug: Placebo

• Registration Number: NCT06147544
• Lead Sponsor: PegBio Co., Ltd.

Brief Summary

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

Detailed Description

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（for cohort 1 and 2） or 18 weeks(for cohort 3) of treatment after screening and complete 8 weeks of safety follow-up.

Study Timeline

• Study Start: 2023-07-06
• Study First Submitted: 2023-08-09
• Study First Submitted QC: 2023-11-24
• Study First Posted: 2023-11-27
• Status Verified: 2024-04
• Primary Completion: 2024-04-16
• Study Completion: 2024-04-16
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Chinese male or female subjects aged 18-60 years (both inclusive).
2. Body weight ≥70 kg(male) or 60 kg(female), and body mass index (BMI) ≥28.0 kg/m2 at screening.
3. Weight change <5% in the past 3 months before screening.

Exclusion Criteria

1. FPG ≥7.0mmol/L or glycosylated hemoglobin (HbA1c) ≥6.5% or diagnosed diabetes
2. FPG <3.9 mmol/L at screening and/or a history of hypoglycemia.
3. History of Cushing's syndrome, polycystic ovaries, or other hereditary endocrine disorders, or obesity caused by secondary factors such as cortisol hormones.
4. Abnormal Thyroid-Stimulating Hormone(TSH), free triiodothyronine(FT3), Free thyroxine(FT4) or diagnosed thyroid dysfunction
5. History of multiple endocrine neoplasia syndrome type 2 (MEN-2) or medullary thyroid carcinoma (MTC).
6. Diagnosed cardiovascular and cerebrovascular diseases with obvious clinical significance within 6 months before screening
7. Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at screening or randomization.
8. PR intervals > 210 msec and/or QRS wave group time limit > 120 msec and/or Corrected QT interval using Fridericia's formula（QTcF）> 450 msec at screening or randomization.
9. Serum amylase or lipase > 3× upper limit of normal (ULN) at screening or before randomization, or previously diagnosed acute/chronic pancreatitis.
10. Low density lipoprotein cholesterol(LDL-C) ≥4.40 mmol/L or triglyceride (TG) ≥5.65 mmol/L.
11. Use of any approved or unapproved drugs or products that have an effect on body weight within 3 months prior to screening
12. History of bariatric surgery for weight loss 1 year before screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PB-718	PB-718	Low dose level of PB-718 administered on the first day of week 1-12(for cohort 1 and 2) or week 1-18(for cohort 3) according to the dose-escalation design Medium dose level of PB-718 administered on the first day of week 1-12(for cohort 1 and 2) or week 1-18(for cohort 3) according to the dose-escalation design High dose level of PB-718 administered on the first day of week 1-12(for cohort 1 and 2) or week 1-18(for cohort 3) according to the dose-escalation design
Placebo	Placebo	Matched placebo administered on the first day of week 1-12(for cohort 1 and 2) or week 1-18(for cohort 3) according to the dose-escalation design

Primary Outcome Measures

Name	Time	Method
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 weeks for cohort 1 and cohort 2 or 26 weeks for cohort 3)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic profile	From the first dose (Day 1 ) of study drug until week 12(for cohort 1 and cohort 2) or week 18(for cohort3)	t1/2
Proportion of participants with ≥5% weight loss	week 12 (for cohort 1 and cohort2) or week 18(for cohort 3)
Change in body weight from baseline	Week12(for cohort 1 and cohort 2) or week 18(for cohort 3)
Change in Fasting Plasma Glucose(FPG) from baseline	week 12(for cohort 1 and cohort 2) or week 18(for cohort 3)

Trial Locations

Locations (1)

Peking University Third Hospital; 🇨🇳 Beijing, Beijing, China