Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JY09

Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JY09, a Long-acting Glucagon-like Peptide-1 Mimetic, in Healthy Subjects

JY09 is a glucagon-like peptide-1 (GLP-1) mimetic generated by genetic fusion of a Exendin-4 dimer to human immunoglobulin Fc.

In this Double-blind, randomized, placebo-controlled trial, 41 healthy subjects received placebo or escalating doses of JY09 on day 1 in the first cohort, and on days 1 and 22 in the following sequential cohort 2-4, and on days 1, 15, and 30 in the cohort 5: cohort 1: 0.3 mg; cohort 2: 0.3 + 0.7 mg; cohort 3: 0.7+1.5 mg; cohort 4: 0.7+3.0 mg; and cohort 5: 0.7 + 1.5 + 6.0 mg. The primary endpoints were the incidence of adverse events and serious adverse events related to JY09. Secondary endpoints included pharmacodynamics and pharmacokinetics parameters, as well as anti-JY09 antibody incidence and titers.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: JY09

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects
• Male's mass is ≥50 kg, female's mass is ≥45 kg, have a body mass index between 18 and 26 kg/m^2
• Subjects or their legal representative signed informed consent
• agree to use instruments of contraception from the time of the first dose until 6 months after the last dose of investigational drug, avoid pregnancy make yourself or your mate
• Able to keep good communication with investigator and comply with the requirements of the clinical trials

Exclusion Criteria:

• Smokers,quitting time less than 3 months , or can't quit smoking during the trial
• Use of any prescription drugs within 4 weeks prior dosing, or over-the-counter medication (vitamins, herbal supplements, dietary supplements) within 2 weeks prior to dosing,or being treated for a direct lower gastrointestinal or using steroids
• Participation in any clinical investigation within 3 months prior to dosing
• Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing
• Significant illness within 2 weeks prior to dosing,and investigator judge doesn't fit to participate in this trial
• A history of clinical significance of abnormal ECG
• A history of diabetes, hyperuricemia and hyperlipidemia
• A history of acute or chronic bronchial spasms
• Have clinical significant gastrointestinal diseases
• Have serious, progressive, or uncontrolled organ or system diseases
• Abuse of drug or alcohol within 12 months before first dosing
• People who are pregnant, nursing mothers, or in the near future plan to be pregnant,or show pregnancy test positive before into group
• Subjects who, in the opinion of the investigator, are in any way unsuitable to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 0.3-mg; Eligible subjects received 0.3 mg placebo or JY09 on day 1 in this cohort	Drug: JY09; Subcutaneous injection; Other Names: Placebo
EXPERIMENTAL: Cohort 0.7-mg; Eligible subjects received 0.3 mg placebo or JY09 on days 1, and 0.7 mg placebo or JY09 on days 22	Drug: JY09; Subcutaneous injection; Other Names: Placebo
EXPERIMENTAL: Cohort 1.5-mg; Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 1.5 mg placebo or JY09 on days 22	Drug: JY09; Subcutaneous injection; Other Names: Placebo
EXPERIMENTAL: Cohort 3.0-mg; Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 3.0 mg placebo or JY09 on days 22	Drug: JY09; Subcutaneous injection; Other Names: Placebo
EXPERIMENTAL: Cohort 6.0-mg; Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 1.0 mg placebo or JY09 on days 15, and 6.0 mg placebo or JY09 on days 30	Drug: JY09; Subcutaneous injection; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events related to JY09	Up to day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics parameters: Cmax	Average Cmax of each dose level	Up To day 42
Pharmacodynamics parameters: AUC	Average AUC follewing single dose of each doase level	Up to day 42
Pharmacodynamics parameters: Half-life	Average Half-life of each dose level	Up to day 42
Pharmacokinetics parameters	OGTT test was conducter predose and 5 days after the target dose in each cohorts	Day 5
Immunogenicity	Anti-JY09 antibody incidence at each dose level	Up To day 42

Collaborators and Investigators

• Sponsor: Beijing Dongfang Biotech Co., Ltd.
• Investigators: Principal Investigator: Juan Li, M.D., The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 26, 2018
• Primary Completion (ACTUAL): December 27, 2018
• Study Completion (ACTUAL): June 22, 2019

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (ACTUAL): April 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: DFBT-JY09-101a

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