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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: INS068 injection
* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: INS068 campared with Insulin degludec, both in Combination with One or Two Oral Antidiabetics
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |