A Trial of INS068 in Patients With Type 2 Diabetes Not Adequately Controlled With One or Two Oral Antidiabetics

Evaluation of the Efficacy and Safety of INS068 Injection and Insulin Degludec Subcutaneous Injection Once Daily in Subjects With Type 2 Diabetes Mellitus Not Adequately Controlled With One or Two Oral Antidiabetics (A Randomized, Open-Label, Two-Arm, Treat-to-Target, Parallel Controlled Trial)

The study is being conducted to evaluate the efficacy and safety of IND068 once daily (QD) in subjects with type 2 diabetes not adequately controlled with one or two oral antidiabetics compared to insulin degludec QD for 16 weeks.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: INS068 injection; Drug: Insulin Degludec

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4064
      • Core Research Group Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3081
      • Austin Health (Heidelberg Repatriation Hospital)
• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 404100
      • Chongqing University Three Gorges Hospital
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College, Huazhong University of Scince and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Affiliated to Southeast University
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital Of China Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710004
      • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Shanghai Xuhui District Central Hospital
    • Shanghai, Shanghai, China, 200062
      • Shanghai Putuo District Central Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • First Hospital of Shanxi Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital,Sichuan University
    • Yibin, Sichuan, China, 644000
      • Yibin Second People's Hospital
• United States
  • California
    • Huntington Park, California, United States, 90255
      • National Research Institute - Huntington Park
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute Inc
    • Los Angeles, California, United States, 90057
      • National Research Institute - Wilshire
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Hialeah, Florida, United States, 33016
      • New Generation of Medical Research
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Ohio
    • Columbus, Ohio, United States, 43201
      • Endocrinology Associates, Inc
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
  • Texas
    • Houston, Texas, United States, 77040
      • Juno Research, LL
    • Houston, Texas, United States, 77074
      • Juno Research, LLC - Southwest Houston Site
    • Houston, Texas, United States, 77054
      • Juno Research, LLC - Medical Center Office
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials

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

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that will not have been performed during normal management of the subject.)
• Age is 18-75 years
• Diagnosed with Type 2 diabetes (according to the diagnosis criteria applicable locally) for at least 3 months
• Treatment with one or two oral anti-diabetic drug (OADs): metformin at astable daily dose of ≥ 1500 mg or maximum tolerated dose (at least 1000mg daily), with or without insulin secretagogue (SU or glinides) or DPP-4 inhibitors or SGLT-2 inhibitors or alpha-glucosidase inhibitors for at least 8 weeks at a stable dose. The dose(s) of OAD other than metformin should be minimum half of the daily maximal dose according to local labelling or maximum tolerated dose.
• Insulin naïve. short-term insulin treatment (consecutive or cumulative treatment of ≤14 days) and insulin treatment for gestational diabetes are allowed.
• HbA1c 7.0-10.0 % (53-85 mmol/mol) (both inclusive)
• BMI 19-40 kg/m2 (both inclusive)

Exclusion Criteria:

• Known or suspected allergy or intolerance to the active substance or to any of the excipients of the investigational medical products
• Severe hypoglycemia during the previous 6 months.
• Hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome during the previous 6 months.
• Cardiovascular disease within the last 12 months, defined as: stroke, decompensated heart failure (New York Heart Association [NYHA] class III or IV), myocardial infarction, or hospitalization for unstable angina pectoris or transient ischemic attack.
• Diagnosis of malignant neoplasms (except basal cell or squamous cell skin cancer, polyps and in-situ carcinomas) within the last 5 years or increased risk of cancer or relapse of cancer.
• Any antidiabetic medication other than permitted in the inclusion criteria or any weight-loss drug within the last 8 weeks..
• Systemic or intra-articular corticosteroids treatment within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INS068; Intervention: Drug: INS068 injection	Drug: INS068 injection; INS068 injected subcutaneously once daily. Treat-to-target dose titration during the trial
Active Comparator: IDeg; Intervention: Drug: insulin Degludec	Drug: Insulin Degludec; Insulin Degludec injected subcutaneously once daily. Treat-to-target dose titration during the trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change from baseline in Glycosylated Haemoglobin after 16 weeks of treatment	Week 0 to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects reaching HbA1c targets	HbA1c <7% or HbA1c ≤6.5%	Week 0 to Week 16
Change in FPG	Change from baseline in FPG after 16 weeks of treatment	Week 0 to Week 16
9-point SMPG profiles	Mean plasma glucose, Postprandial and nocturnal increments, Fluctuation of 9-point SMPG. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner,120 minutes after start of dinner, before bedtime, at 4 am and before breakfast.	Week 0 to Week 16
Pre-breakfast SMPG	Mean plasma glucose, Within-subject variability of pre-breakfast SMPG.	Week 0 to Week 16
Titration target	Proportion of subjects and time reaching titration targets	Week 0 to Week 16
Numbers of hypoglycaemic episodes according to 2017 ADA/EASD classfication	Classification of hypoglycaemia: Level 1(glucose level below 3.9 mmol/L), Level 2(glucose level below 3.0 mmol/L) and Level 3(Severe hypoglycemia, denotes severe cognitive impairment requiring external assistance for recovery).	Week 0 to Week 16
Numbers of injection site reactions	The injection site reactions was assessed during the treatment period of 16 weeks.	Week 0 to Week 16
Frequency and severity of adverse events	Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities, no or minimal medical treatment. Moderate: marked symptoms, interference with subject's daily activities，and medical treatment for alleviation without grave or permanent injury to the subject. . Severe: considerable interference with subject's daily activities， and intensive treatment and intervention needed.	Week 0 to Week 16 + 14 days follow-up
Anti-drug Antibodies: Anti-INS068 Antibodies	Number of Participants Positive or Negative for Anti-INS068 Antibodies were reported.	Week 0 to Week 16+14 days follow-up
Changes in Body Weight	Change of body weight was evaluated from Week 0 to Week 16	Week 0 to Week 16
Changes in Body Mass Index	Change of Body Mass Index was evaluated from Week 0 to Week 16	Week 0 to Week 16
Change in Health Related Quality of Life Questionnaire (SF -36)	Change from baseline in scores of Health-Related Quality of Life Questionnaire after 16 weeks of treatment. The questionnaire contains 36 items across 8 domains and 2 summary scores. Score range: 0 (worst score) to 100 (best score)	Week 0 to Week 16
Serum INS068 concentration	To evaluate PK of INS068	Week 0 to Week 16

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): May 28, 2022
• Study Completion (Actual): May 28, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: January 1, 2022

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; Insulin
• Other Study ID Numbers: INS068-201

Drug and device information, study documents

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