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 Weekly Semaglutide (COMBINE 2)

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 semaglutide taken once a week 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 semaglutide. Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries. Participants will get IcoSema or semaglutide, which they must inject once a week 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 have 18 clinic visits, 34 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls. At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. 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 Once Weekly Semaglutide, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With a GLP 1 Receptor Agonist. COMBINE 2

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: IcoSema
* Drug: Semaglutide 1 mg


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% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes. Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above. Body mass index (BMI) below or equal to 40.0 kg/m^2. 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 (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening. 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. 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 get once weekly dose | Drug: IcoSema<br>* IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.<br>|
| Experimental: Semaglutide<br>Participants will get once weekly dose | Drug: Semaglutide 1 mg<br>* Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glycated haemoglobin (HbA1c) | Percentage-point | From baseline week 0 (V2) to week 52 (V54) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting plasma glucose (FPG) | Measured in mmol/L | From baseline week 0 (V2) to week 52 (V54) | 
| Change in body weight | Measured in Kg | From baseline week 0 (V2) to week 52 (V54) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or 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) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) | Number of episodes | From baseline week 0 (V2) to week 57 (V56) | 
| Number of severe hypoglycaemic episodes (level 3) | Number of episodes | From baseline week 0 (V2) to week 57 (V56) |