A Research Study to See if Kidney Damage in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity Can be Reduced by CagriSema Compared to Semaglutide, Cagrilintide and Placebo

Study Overview
=================
Brief Summary
-----------------
This study will look if CagriSema can lower kidney damage in people with chronic kidney disease (CKD), type 2 diabetes (T2D) and overweight or obesity. CagriSema is a new investigational medicine. CagriSema cannot yet be prescribed by doctors. The study will compare CagriSema to the 2 medicines semaglutide and cagrilintide, when they are taken alone. It will also compare CagriSema to a dummy medicine (also called placebo) without any active ingredient. Participant will either get CagriSema 2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg or placebo. Which treatment participant will get is decided by chance (like flipping a coin). Study doctor will not know which of the study medicines participant will get. For each participant, the study will last for about 35 weeks.

Official Title
-----------------
Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema 2.4 mg/2.4 mg) Once Weekly Versus Semaglutide 2.4 mg, Cagrilintide 2.4 mg and Placebo in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity

Conditions
-----------------
Chronic Kidney Disease, Type 2 Diabetes, Obesity

Intervention / Treatment
-----------------
* Drug: Cagrilintide
* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female. Age 18 years or above at the time of signing the informed consent. Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening. Body mass index (BMI) ≥ 27.0 kilograms per meter square (kg/m^2) at screening. BMI will be calculated in the eCRF (electronic case report form) based on height and body weight at screening. HbA1c less than or equal to (≤) 10.5% (91 millimoles per mole [mmol/mol]) as assessed by central laboratory at screening. Kidney impairment defined by serum creatinine and cystatin C-based eGFR ≥ 15 and < 90 milliliters per minutes per 1.73^m^2 (mL/min/1.73 m^2) (CKD-EPI 2021) as assessed by central laboratory at screening. Albuminuria defined by UACR ≥ 100 and < 5000 milligram per gram (mg/g) as assessed by central laboratory at screening. Treatment with maximum labelled or tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated, in the opinion of the investigator. Treatment dose must be stable for at least 30 days prior to screening. 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. Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations. Use of any glucagon-like peptide-1 receptor agonist (GLP-1RA) (including medication with GLP-1RA activity, e.g., GIP/GLP-1RA) or amylin analogue within 60 days prior to screening. Myocardial infarction, stroke, transient ischaemic attack, or hospitalization for unstable angina pectoris within 60 days before screening. Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening. 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 malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in-situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN) within 5 years before screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: CagriSema 2.4 mg/2.4 mg<br>Participants will receive 2.4 milligram (mg) cagrilintide and 2.4 mg semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks. | Drug: Cagrilintide<br>* Participants will receive Cagrilintide subcutaneously.<br>Drug: Semaglutide<br>* Participants will receive semaglutide subcutaneously.<br>|
| Experimental: Semaglutide 2.4 mg<br>Participants will receive semaglutide 2.4 mg and placebo matched to cagrilintide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks. | Drug: Semaglutide<br>* Participants will receive semaglutide subcutaneously.<br>Drug: Placebo<br>* Participants will receive placebo matched to cagrilintide or placebo matched to semaglutide subcutaneously.<br>|
| Experimental: Cagrilintide 2.4 mg<br>Participants will receive cagrilintide 2.4 mg and placebo matching to semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks. | Drug: Cagrilintide<br>* Participants will receive Cagrilintide subcutaneously.<br>Drug: Placebo<br>* Participants will receive placebo matched to cagrilintide or placebo matched to semaglutide subcutaneously.<br>|
| Placebo Comparator: Placebo<br>Participants will receive 2.4 mg placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously once weekly for 26 weeks. | Drug: Placebo<br>* Participants will receive placebo matched to cagrilintide or placebo matched to semaglutide subcutaneously.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary albumin-to-creatinine ratio (UACR) | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 26) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in estimated glomerular filtration rate (eGFR) (creatinine and cystatin C-based chronic kidney disease (CKD)-Epidemiology Collaboration equation (EPI) 2021) | Measured in milliliters per minute per 1.73 meters square (mL/min/1.73 m^2). | From baseline (week 0) to end of treatment (week 26) | 
| Change in eGFR (creatinine-based CKD-EPI 2021) | Measured in mL/min/1.73 m^2. | From baseline (week 0) to end of treatment (week 26) | 
| Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 26) | 
| Achievement of greater than or equal to (≥) 5 % weight reduction | Count of participants. | From baseline (week 0) to end of treatment (week 26) | 
| Achievement of ≥ 10 % weight reduction | Count of participants. | From baseline (week 0) to end of treatment (week 26) | 
| Change in waist circumference | Measured in centimeter (cm). | From baseline (week 0) to end of treatment (week 26) | 
| Change in glycated haemoglobin (HbA1c) | Measured in %-points. | From baseline (week 0) to end of treatment (week 26) | 
| Change in systolic blood pressure | Measured in millimeters of mercury (mmHg). | From baseline (week 0) to end of treatment (week 26) | 
| Change in diastolic blood pressure | Measured in mmHg. | From baseline (week 0) to end of treatment (week 26) | 
| Number of treatment emergent adverse events (TEAEs) | count of events. | From baseline (week 0) to end of study (week 32) | 
| Number of treatment emergent serious adverse events (SAEs) | count of events. | From baseline (week 0) to end of study (week 32) | 
| Number of clinically significant hypoglycaemic episodes (level 2) ( blood glucose less than [<] 3.0 millimoles per liter [mmol/L] (54 milligram per deciliter [mg/dL])) | Count of episodes. | From baseline (week 0) to end of study (week 32) | 
| Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold | Count of episodes. | From baseline (week 0) to end of study (week 32) |