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

A 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.

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: PB-718; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liting Sun, Master; Phone Number: 0512 62956128; Email: liting.sun@pegbio.com
• Study Contact Backup: Name: Michael Xu, PhD; Phone Number: 0512 62956129; Email: michael.xu@pegbio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: PB-718; Administered subcutaneously once a week
Placebo Comparator: 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	Drug: Placebo; Administered subcutaneously once a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 weeks for cohort 1 and cohort 2 or 26 weeks for cohort 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile	Cmax	From the first dose (Day 1 ) of study drug until week 12 (for cohort 1 and cohort 2) or week 18(for cohort 3)
Pharmacokinetic profile	Tmax	From the first dose (Day 1 ) of study drug until week 12(for cohort 1 and cohort 2) or week 18(for cohort 3)
Pharmacokinetic profile	Area under the concentration-time curve over dosing interval(AUC0-tau）	From the first dose (Day 1 ) of study drug until week 12(for cohort 1 and cohort 2) or week 18(for cohort 3)
Pharmacokinetic profile	Area under the concentration-time curve from time zero to the time of the last quantifiable concentration（AUC0-last）	From the first dose (Day 1 ) of study drug until week 12(for cohort 1 and cohort2) or week 18(for cohort 3)
Pharmacokinetic profile	t1/2	From the first dose (Day 1 ) of study drug until week 12(for cohort 1 and cohort 2) or week 18(for cohort3)
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)

Collaborators and Investigators

• Sponsor: PegBio Co., Ltd.
• Investigators: Principal Investigator: Dongyang liu, PhD, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Actual): April 16, 2024
• Study Completion (Actual): April 16, 2024

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: November 24, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PB718101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No