Multiple-dose Tolerability and Pharmacokinetic of IBI362 in Chinese Patients With T2DM

A Multiple Dose Human Tolerability and Pharmacokinetic Study of IBI362 in Chinese Patients With Type 2 Diabetes Mellitus and Poor Glycemic Control

This trial is aimed to investigate the safety, tolerability, PK and PD of multiple subcutaneous injections of IBI362 in Chinese patients with type 2 diabetes who have poor glycemic control after lifestyle or metformin intervention

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: IBI362; Drug: Placebo; Drug: Dulaglutide

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled trial, the first trial to assess the safety, tolerability, and PK/PD of IBI362 administered as multiple injections in Chinese patients with type 2 diabetes. The investigators and subjects will be blinded to the study drug IBI362 and placebo. Dulaglutide will be used as an open-label active control group. In this trial, 42 eligible patients will be recruited and randomly allocated to three cohorts. Each corhot will be randomized as an 8:4:2 ratio to IBI362 (n = 8), placebo (n = 4), and Dulaglutide 1.5 mg (n = 2).

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • China Japan Friendship Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

* Eligibility Criteria： Inclusion Criiteria:

1. Male or female 18 to 75 years of age at the time of consent.
2. T2D patients with poorly controlled blood glucose treated with lifestyle intervention or stable dose of metformin (≥ 1000mg/day or maximum tolerated dose) within 2 months prior to screening.
3. HbA1c 7.5% ≤ 11.0% by local laboratory at screening.
4. Body mass index 20 ≤ BMI ≤ 35 kg/m2.

Exclusion Criteria:

1. Type 1 diabetes, special types of diabetes, or gestational diabetes.
2. Ketoacidosis or lactic acidosis within 6 months prior to screening.
3. History of severe hypoglycaemic episodes within 6 months prior to screening.
4. Acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, coronary intervention (except diagnostic angiography), transient ischemic attack (TIA), cerebrovascular accident, acute and chronic heart failure within 6 months before screening.
5. Clinically symptomatic liver disease, acute or chronic hepatitis, or transaminases (ALT and AST) and alkaline phosphatase (ALP) > 2 times the upper limit of normal and total bilirubin above the upper limit of normal at screening.
6. The patient was previously diagnosed with autonomic neuropathy, manifested as urinary retention, resting tachycardia, orthostatic hypotension and diabetic diarrhea.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IBI362 low dose cohort; Participants receive low dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection.	Drug: IBI362; Administrated by subcutaneous injection; Drug: Placebo; Administrated by subcutaneous injection; Drug: Dulaglutide; Administrated by subcutaneous injection
Experimental: IBI362 medium dose cohort; Participants receive medium dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection	Drug: IBI362; Administrated by subcutaneous injection; Drug: Placebo; Administrated by subcutaneous injection; Drug: Dulaglutide; Administrated by subcutaneous injection
Experimental: IBI362 high dose cohort; Participants receive high dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection	Drug: IBI362; Administrated by subcutaneous injection; Drug: Placebo; Administrated by subcutaneous injection; Drug: Dulaglutide; Administrated by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the number and incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of IBI362 compared with placebo	Number of subjects with treatment emergent adverse events and serious adverse events through the end of the follow-up period	From the first dose of study drug to week 19

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The PK/PD parameters of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the Peak Plasma Concentration (Cmax) of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the Area under the plasma concentration versus time curve (AUC) of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the Fasting Blood Glucose (FBG ) of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the Glucagon of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the Insulin of IBI362 in patients with T2DM		From Baseline to week 12
Evaluate the C-peptide of IBI362 in patients with T2DM		From Baseline to week 12
Number of Participants With Anti-IBI362 Antibodies	Serum samples will be analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-IBI362 binding antibodies. Positive samples will be subsequently tested in a receptor-ligand binding bioassay for anti-IBI362 neutralizing antibodies.	From the first dose of study drug to week 19

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Publications and helpful links

General Publications

• Jiang H, Pang S, Zhang Y, Yu T, Liu M, Deng H, Li L, Feng L, Song B, Han-Zhang H, Ma Q, Qian L, Yang W. A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes. Nat Commun. 2022 Jun 24;13(1):3613. doi: 10.1038/s41467-022-31328-x.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2020
• Primary Completion (Actual): May 28, 2021
• Study Completion (Actual): May 28, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 7, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

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; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: CIBI362A101

Drug and device information, study documents

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