A Research Study Looking at How Well a Combination of the Medicines Semaglutide and NNC0480-0389 Works in People With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This study is looking at semaglutide in combination with a potential new medicine (NNC0480-0389) in people with type 2 diabetes. The study is being conducted to see how well semaglutide, in combination with different doses of NNC0480-0389, work to lower blood sugar levels. Results from this study will be used to select the doses of the two medicines for other studies. Participants will either get: Semaglutide (a medicine doctors can already prescribe for treatment of type 2 diabetes) in combination with NNC0480-0389 (a potential new medicine) or placebo (a 'dummy' medicine that looks like the medicines but without any medicine). NNC0480-0389 alone, or semaglutide alone which treatment participant get is decided by chance. Participant will need to take 2-3 injections once every week during the study. One injection will be with semaglutide or placebo and 1-2 injections will be with NNC0480-0389 or placebo. Participant must inject the study medicines themself into the stomach, thigh, or upper arm. The study will last for about 41weeks. Participant will have 20 clinic visits. Participant will have blood samples taken at all clinic visits. At 3 clinic visits, participant will also have an electrocardiogram (ECG). This is a test to check participants heart. Participant will have their eyes checked before or at the start of the study and at the end of the study. Women can only take part in the study if they are not able to become pregnant

Official Title
-----------------
Investigation of the Safety and Efficacy of Semaglutide s.c. in Combination With NNC0480-0389 in Participants With Type 2 Diabetes - a Dose Finding Study

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: NNC0480-0389
* Drug: Semaglutide
* Drug: Placebo (NNC080-0389)
* Drug: Placebo (semaglutide)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening Participants treated with diet and exercise as monotherapy or in combination with stable daily dose(s) greater than or equal to 90 days before screening of any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) BMI greater than or equal to 25 and below 40 kg/m^2 Exclusion Criteria: Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days and prior insulin treatment for gestational diabetes are allowed Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 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 Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic cardiovascular, gastrointestinal, or endocrinological conditions (except conditions associated with T2D)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2.4 mg semaglutide + 2.4 mg NNC0480-0389<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide. | Drug: NNC0480-0389<br>* A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.<br>Drug: Semaglutide<br>* A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.<br>|
| Placebo Comparator: Placebo (semaglutide) + placebo ( 2.4 mg NNC0480-0389)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide). | Drug: Placebo (NNC080-0389)<br>* A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.<br>Drug: Placebo (semaglutide)<br>* A weekly dose of placebo (semaglutide). The study will last for about 41weeks.<br>|
| Experimental: 2.4 mg semaglutide + 7.2 mg NNC0480-0389<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide | Drug: NNC0480-0389<br>* A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.<br>Drug: Semaglutide<br>* A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.<br>|
| Experimental: 2.4 mg semaglutide + 12.0 mg NNC0480-0389<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide | Drug: NNC0480-0389<br>* A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.<br>Drug: Semaglutide<br>* A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.<br>|
| Experimental: 2.4 mg semaglutide + 21.6 mg NNC0480-0389<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide | Drug: NNC0480-0389<br>* A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.<br>Drug: Semaglutide<br>* A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.<br>|
| Experimental: NNC0480-0389 + placebo (semaglutide)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. placebo (semaglutide) | Drug: NNC0480-0389<br>* A weekly dose of NNC0480-0389, dose increased in each cohort. The study will last for about 41weeks.<br>Drug: Placebo (semaglutide)<br>* A weekly dose of placebo (semaglutide). The study will last for about 41weeks.<br>|
| Placebo Comparator: Placebo (semaglutide) + placebo ( 7.2 mg NNC0480-0389)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide). | Drug: Placebo (NNC080-0389)<br>* A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.<br>Drug: Placebo (semaglutide)<br>* A weekly dose of placebo (semaglutide). The study will last for about 41weeks.<br>|
| Placebo Comparator: Placebo (semaglutide) + placebo ( 12.0 mg NNC0480-0389)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide). | Drug: Placebo (NNC080-0389)<br>* A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.<br>Drug: Placebo (semaglutide)<br>* A weekly dose of placebo (semaglutide). The study will last for about 41weeks.<br>|
| Placebo Comparator: Placebo (semaglutide) + placebo ( 21.6 mg NNC0480-0389)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. placebo (semaglutide). | Drug: Placebo (NNC080-0389)<br>* A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.<br>Drug: Placebo (semaglutide)<br>* A weekly dose of placebo (semaglutide). The study will last for about 41weeks.<br>|
| Experimental: Semaglutide 2.4 mg + placebo (NNC0480-0389)<br>subjects will receive once weekly subcutaneous (s.c., under the skin) dose of placebo (NNC0480-0389) co-administered with s.c. semaglutide. | Drug: Semaglutide<br>* A weekly dose of semaglutide, same dose in each cohort. The study will last for about 41weeks.<br>Drug: Placebo (NNC080-0389)<br>* A weekly dose of placebo (NNC0480-0389). The study will last for about 41weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | percentage-point | From baseline (week 0) to visit 24 (week 34) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting plasma glucose (FPG) | measured in mmol/L | From baseline (week 0) to visit 24 (week 34) | 
| Change in body weight (kg) | measured in kg | From baseline (week 0) to visit 24 (week 34) | 
| Change in body weight (%) | measured in percent | From baseline (week 0) to visit 24 (week 34) | 
| Change in waist circumference | measured in cm | From baseline (week 0) to visit 24 (week 34) | 
| Change in systolic blood pressure (SBP) | measured in mmHg | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in total cholesterol | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in high-density lipoprotein (HDL) cholesterol | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in low-density lipoprotein (LDL) cholesterol | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in very-low-density lipoprotein (VLDL) cholesterol | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in triglycerides | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in free fatty acids | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in Apolipoprotein B (ApoB) | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Relative change in high sensitivity C-Reactive Protein (hsCRP) | ratio | From baseline (week 0) to visit 24 (week 34) | 
| Number of treatment-emergent adverse events (TEAEs) | Count of events | From baseline (week 0) to visit 25 (week 39) |