A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

Study Overview
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Brief Summary
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This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine taken daily with insulin aspart in people with type 2 diabetes.The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries. Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach. The study will last for about 1 year and 1 month. Participants will be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Official Title
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A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL Combined With Insulin Aspart, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin. COMBINE 3

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: IcoSema
* Drug: Insulin glargine
* Drug: insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female and age above or equal to 18 years at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus 180 days or more before screening. HbA1c of 7.0-10.0 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses 90 days or more before screening: Metformin Sulfonylureas(a) Meglitinides (glinides)(a) DPP-4 inhibitors(a) Sodium-glucose co-transporter 2 inhibitors Alpha-glucosidase-inhibitors Thiazolidinediones Marketed oral combination products only including the products listed above. Body mass index (BMI) less than or equal to 40.0 kg/m^2. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation. Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method. Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid, hormones, or systemic corticosteroids). Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. Any episodes of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records. Presence or history of pancreatitis (acute or chronic) within 180 days before screening. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. Chronic heart failure classified as being in New York Heart Association Class IV at screening. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non dilated examination.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IcoSema<br>Participants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period. | Drug: IcoSema<br>* Participants will receive a once weekly subcutanous (s.c.) injection of IcoSema, on the same day every week for 52 weeks.<br>|
| Active Comparator: Insuling glargine/insulin aspart<br>Participants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart. | Drug: Insulin glargine<br>* Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.<br>Drug: insulin aspart<br>* Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Percent-points | From baseline week 0 (V2) to week 52 (V54) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Kg | From baseline week 0 (V2) to week 52 (V54) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) | Number of episodes | From week 0 (V52) to week 52 (V54) | 
| Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 | Percentage of readings | From week 48 (V50) to week 52 (V54) | 
| Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 | Percentage of readings | From week 48 (V50) to week 52 (V54) | 
| Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 | Percentage of readings | From week 48 (V50) to week 52 (V54) | 
| Change in fasting plasma glucose (FPG) | mmol/L | From baseline week 0 (V2) to week 52 (V54) | 
| Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction | Score 0-36. The higher the score the greater the satisfaction with treatment. | From baseline week 0 (V2) to week 52 (V54) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From baseline week 0 (V2) to week 57 (V56) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) | Number of episodes | From baseline week 0 (V2) to week 57 (V56) | 
| Weekly insulin dose (total) | Units | From week 50 (V52) to week 52 (V54) |