A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight

Study Overview
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Brief Summary
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This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight. Participants will either get CagriSema or a dummy medicine. Which treatment they get is decided by chance. The study will last for about 1½ years. Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period.

Official Title
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Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema s.c. 2.4 mg/2.4 mg) Once-weekly in Participants With Overweight or Obesity and Type 2 Diabetes

Conditions
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Overweight, Obesity, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Cagrilintide
* Drug: Semaglutide
* Drug: Placebo cagrilintide
* Drug: Placebo semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age above or equal to 18 years at the time of signing informed consent BMI greather than or equal to 27.0 kg/m^2 Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening Treatment with either lifestyle intervention, or treatment with 1-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), thiazolidinediones, or sulphonylureas (SU)s as a single agent or in combination) according to local label Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and dosing frequency) for at least 90 days before screening HbA1c 7%-10% (53-86 mmol/mol) (both inclusive) as measured by the central laboratory at screening Exclusion Criteria: Clinically significant or severe hypoglycaemia within 6 months before screening or history of hypoglycaemia unawareness Renal impairment with estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2, as measured by the central laboratory at 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.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CagriSema<br>Cagrilintide + semaglutide once weekly | Drug: Cagrilintide<br>* Cagrilintide administered subcutaneously (s.c., under the skin) once-weekly<br>Drug: Semaglutide<br>* Semaglutide administered subcutaneously (s.c., under the skin) once-weekly<br>|
| Placebo Comparator: Placebo<br>Placebo cagrilintide + semaglutide once weekly | Drug: Placebo cagrilintide<br>* Placebo cagrilintide administered subcutaneously (s.c., under the skin) once-weekly<br>Drug: Placebo semaglutide<br>* Placebo semaglutide administered subcutaneously (s.c., under the skin) once-weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of greater than or equal to (≥) 5% weight reduction | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of ≥ 20% weight reduction | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 
| Relative change in body weight | Measured in %. | From baseline (week 0) to week 20 | 
| Change in waist circumference | Measured in centimeter (cm). | From baseline (week 0) to end of treatment (week 68) | 
| Change in Glycated Haemoglobin (HbA1c) | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) | 
| Change in Systolic Blood Pressure (SBP) | Measured in millimeter of mercury (mmHg). | From baseline (week 0) to end of treatment (week 68) | 
| Change in Impact of Weight on Quality Of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score | Measured in score points. | From baseline (week 0) to end of treatment (week 68) | 
| Change in Short Form-36 Version 2.0 Health Survey Acute (SF-36v2 Acute) Physical Functioning score | Measured in score points. | From baseline (week 0) to end of treatment (week 68) | 
| Change in body weight | Measured in kilogram (kg). | From baseline (week 0) to end of treatment (week 68) | 
| Change in body mass index (BMI) | Measured in kilogram per meter square (kg/m^2). | From baseline (week 0) to end of treatment (week 68) | 
| Improvement in weight category (BMI, underweight below 18.5, normal weight 18.5 to below 25, overweight 25.0 to below 30, obesity class I 30 to below 35, obesity class II 35 to below 40, obesity class III above 40) | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of HbA1c less than or equal to (≤) 6.5% | Count of participant. | At end of treatment (week 68) | 
| Change in Fasting Plasma Glucose (mmol/L) | Measured in millimoles per liter (mmol/L). | From baseline (week 0) to end of treatment (week 68) | 
| Change in Fasting Plasma Glucose (mg/dL) | Measured in milligram per deciliter (mg/dL) | From baseline (week 0) to end of treatment (week 68) | 
| Ratio to baseline in fasting serum insulin | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) | 
| Change in Diastolic Blood Pressure (DBP) | Measured in mmHg. | From baseline (week 0) to end of treatment (week 68) | 
| Ratio to baseline in C-reactive protein (CRP) | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) | 
| Ratio to baseline in lipids: Total cholesterol, High-density lipoprotein (HDL) cholesterol, Low-density lipoprotein (LDL) cholesterol, Very low-density lipoprotein (VLDL) cholesterol, Triglycerides and Free fatty acids | Measured in ratio. | From baseline (week 0) to end of treatment (week 68) | 
| Change in IWQOL-Lite-CT: Total score, Physical and Psycosocial score | IWQOL-Lite-CT is a 20-item clinical outcomes assessment (COA) instrument used to assess the impact of body weight changes in obesity studies on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. Score ranges for composite score (physical composite, psychosocial composite and physical function composite) and Total score is 0-100. Higher scores indicate better level of functioning. | From baseline (week 0) to end of treatment (week 68) | 
| Change in Control of Eating Questionnaire (CoEQ): Craving Control score, Positive Mood score, Craving for Sweet score, Craving for Savoury food score, Hunger score and Satiety score | CoEQ is a 19-item multidimensional patient-reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), and craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). Higher score represents a greater level of Craving Control. | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite-CT Physical Function score | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of at least 3.7-point increase (yes/no) in SF-36v2 Acute Physical Functioning score | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 
| Change in IWQOL-Lite-CT Physical Function score |  | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite -CT Physical Function score for subgroup | Count of participant. | From baseline (week 0) to end of treatment (week 68) | 
| Continuous glucose monitoring: Change in mean glucose (mmol/L) | Measured in mmol/L. | From baseline (week 0) to end of treatment (week 68) | 
| Continuous glucose monitoring: Change in mean glucose (mg/L) | Measured in mg/L. | From baseline (week 0) to end of treatment (week 68) | 
| CGM: Change in time above range (TAR) >10.0 mmol/L (>180 mg/dL) | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) | 
| CGM: Change in time in range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) | 
| CGM: Change in time above high range (TAHR) >13.9 mmol/L (>250 mg/dL) | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) | 
| CGM: Change in time in tight range (TITR) 3.9-7.8 mmol/L (71-140 mg/dL) | Measured in %-points. | From baseline (week 0) to end of treatment (week 68) | 
| CGM: Within-day glycaemic variability (% CV) | Measured in %. | At end of treatment (week 68) | 
| Number of Treatment Emergent Adverse Events (TEAEs) | Count of events. | From baseline (week 0) to end of study (week 75) | 
| Number of Treatment Emergent Serious adverse events (TESAEs) | Count of events. | From baseline (week 0) to end of study (week 75) | 
| Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) | Count of episodes. | From baseline (week 0) to end of study (week 75) | 
| 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 75) |