a Study of JY09 in Chinese Healthy Subjects

Randomized,Double-blind,Placebo-controlled,Dose-escalating Phase I,Healthy Subjects Study of JY09,a Recombinant GLP-1 Receptor Agonist

JY09，is a recombinant glucagon-like peptide-1 (GLP-1) receptor agonist,constructed with Exendin-4 and human Immunoglobulin G2 (IgG2) Fc fragment.Preclinical studies show that JY09 exhibit the expected GLP-1-mediated pharmacological effects on insulin secretion,glucose covering and islet cell recovering,as well as good tolerance and safety.JY09 has been approved by China food and drug administration(CFDA) to enter the clinical research stage(Grant number 2016L04254).This study is designed to assess the safety,tolerability,pharmacokinetics,pharmacodynamics and potential immunogenicity of JY09 in healthy Chinese volunteers.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: JY09; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 1

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 equal or greater than 50 kg, female's mass is equal or greater than 45 kg,have a body mass index (BMI) between 18 and 28 kilograms per square meter (kg/m^2), inclusive.
• The subjects sign informed consent form voluntarily.
• The subjects 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.
• Participants will be 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 or family history of long QT syndrome (grandparents, parents and siblings)
• Have a family history of diabetes (grandparents, parents and siblings).
• Have a history of acute or chronic bronchial spasms(including after treatment or no treatment of asthma and chronic obstructive pulmonary disease )
• Have a history of drug allergy or atopic disease allergy(asthma, urticaria, eczema, dermatitis),or allergy history of trail drugs or similar drugs.
• Have gastrointestinal diseases,such as history of liver disease, gastrointestinal disease,gastrointestinal surgery (appendix removed except) or chronic pancreatitis, or history of idiopathic acute pancreatitis that,in the opinion of the investigator,is clinical significant.
• Have personal or family history of medullary thyroid cancer (MTC) or a hereditary disease that induce MTC .
• Have a history of immunodeficiency disease,including human immunodeficiency virus (HIV) antibody positive.
• Have a history of needlesickness that,in the opinion of the investigator,is clinical significant.
• Have an unknown cause of infection.
• In screening,any abnormal results of physical examination, vital signs,electrocardiogram (ECG) and clinical laboratory that,in the opinion of the investigator,is clinical significant.
• Hepatitis b surface antigen or hepatitis c antibody positive, or treponema pallidum antibody positive.
• Abuse of drug or alcohol within 12 months before first dosing,or in screening found evidence of abuse in laboratory tests.
• People who are pregnant, nursing mothers, or in the near future plan to be pregnant,or show pregnancy test positive before into group.
• In screening,lying position (after 3 minutes rest) systolic blood pressure outside the range 90 ~ 140 MMHG, or diastolic blood pressure outside the range 50-90 MMHG, or pulse (HR) outside the range 40 ~ 100 bpm, boundary value into the group.
• Have chang of weight > 3 kg within 3 months by self-report.
• 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: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3mg JY09(cohort 1); 0.3mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Experimental: 1.5mg JY09(cohort 1); 1.5mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Experimental: 6.0mg JY09(cohort 1); 6.0mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Placebo Comparator: Placebo(cohort 1); Placebo administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: Placebo; 1ml/bottle
Experimental: 0.7mg JY09(cohort2); 0.7mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Experimental: 3.0mg JY09(cohort2); 3.0mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Experimental: 12.0mg JY09(cohort2); 12.0mg JY09 administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: JY09; 2mg/1ml/bottle
Placebo Comparator: Placebo(cohort 2); Placebo administered once subcutaneous injection to healthy participants in 1 of 3 treatment periods	Drug: Placebo; 1ml/bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK)	Area Under the Concentration Versus Time Curve (AUC) of JY09	Baseline through day29 of period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunogenicity	A measure of the body's immune response to JY09	Baseline through day29 of period
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	Weight loss of subject is greater than 3 kg will be recorded as adverse events in a month	baseline to 3 months(cohort1 and cohort 2)
Pharmacodynamics (PD）	Area Under the Concentration Versus Time Curve (AUC) of Glucose	Baseline through day29 of period

Collaborators and Investigators

• Sponsor: Beijing Dongfang Biotech Co., Ltd.

Publications and helpful links

General Publications

• Thorkildsen C, Neve S, Larsen BD, Meier E, Petersen JS. Glucagon-like peptide 1 receptor agonist ZP10A increases insulin mRNA expression and prevents diabetic progression in db/db mice. J Pharmacol Exp Ther. 2003 Nov;307(2):490-6. doi: 10.1124/jpet.103.051987. Epub 2003 Sep 15.
• Bradley DP, Kulstad R, Schoeller DA. Exenatide and weight loss. Nutrition. 2010 Mar;26(3):243-9. doi: 10.1016/j.nut.2009.07.008.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 20, 2016
• First Posted (Estimate): November 23, 2016

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: GLP-1 receptor agonist
• Other Study ID Numbers: DFBT-JY09-1

Plan for Individual participant data (IPD)

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