A Research Study to Investigate How Well NNC0165-1875 in Combination With Semaglutide Works in People With Obesity

Study Overview
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Brief Summary
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The study is looking at a new medicine to help people lose weight. In this study participants will either get semaglutide and NNC0165-1875 or semaglutide and a dummy medicine (placebo). Which treatment participants get is decided by chance. Participants will get 2 injections per week, on the same day. Participants will have to take the study medicine by use of a pre-filled pen. A pen is a medical tool with a needle used for injections under the skin. The study doctor or staff will show participants how. The study will last for about 26 weeks. Participants will have 17 visits at the clinic with the study doctor. At 4 of the clinic visits participants cannot eat and drink (water is allowed until 2 hours prior to the visit) for 8 hours before the visit.Women: Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period. Women who are able to become pregnant can participate if they agree to use contraception during the study.

Official Title
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Investigation of Efficacy and Safety of NNC0165-1875 as add-on to Semaglutide for Weight Management in Subjects With Obesity

Conditions
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Obesity

Intervention / Treatment
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* Drug: Semaglutide 2.4 mg and NNC0165-1875 2.0 mg
* Drug: Semaglutide 2.4 mg and placebo 2.0 mg
* Drug: Semaglutide 2.4 mg and NNC0165-1875 1.0 mg
* Drug: Semaglutide 2.4 mg and placebo 1.0 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Male or female, age above or equal to 18 years at the time of signing informed consent. BMI 30.0-45.0 kg/m^2 (both inclusive) at the screening visit. Exclusion Criteria: HbA1c greater than or equal to 48 mmol/mol (6.5%) as measured by a central laboratory at screening. History of type 1 or type 2 diabetes mellitus. Treatment with glucose-lowering agent(s) within 90 days before screening.

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
Interventional Model Description: Part 1: is a 16-week study were one group of participants will receive two doses of NNC0165-1875 a week, in combination with one injection dose of semaglutide a week. The other group will receive a placebo. Part 2: is a 40-week study were one group of participants will receive one dose of NNC0165 a week, in combination with one injection dose of semaglutide a week. The other group will receive a placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 2.4 mg and NNC0165-1875 2.0 mg<br>Participants will receive two doses of NNC0165-1875 as an add on to semaglutide s.c. 2.4 mg | Drug: Semaglutide 2.4 mg and NNC0165-1875 2.0 mg<br>* NNC0165-1875 will be co-escalated once-weekly subcutaneously with semaglutide every 2 weeks for the first 4 weeks, and every 4 weeks for the next 8 weeks until final target dose levels are reached.<br>|
| Placebo Comparator: Semaglutide 2.4 mg and placebo 2.0 mg(NNC0165-1875 2.0 mg)<br>Participants will receive placebo as an add on to semaglutide 2.4 mg. | Drug: Semaglutide 2.4 mg and placebo 2.0 mg<br>* NNC0165-1875 placebo will be co-escalated subcutaneously once-weekly with semaglutide every 2 weeks for the first 4 weeks, and every 4 weeks for the next 8 weeks until final target dose levels are reached.<br>|
| Experimental: Semaglutide 2.4 mg and NNC0165-1875 1.0 mg<br>Participants will receive two doses of NNC0165-1875 as an add on to semaglutide s.c. 2.4 mg | Drug: Semaglutide 2.4 mg and NNC0165-1875 1.0 mg<br>* NNC0165-1875 will be co-escalated subcutaneously once-weekly with semaglutide every 2 weeks for the first 4 weeks, and every 4 weeks for the next 8 weeks until final target dose levels are reached.<br>|
| Placebo Comparator: Semaglutide 2.4 mg and placebo 1.0 mg(NNC0165-1875 1.0 mg)<br>Participants will receive placebo as an add on to semaglutide 2.4 mg. | Drug: Semaglutide 2.4 mg and placebo 1.0 mg<br>* NNC0165-1875 placebo will be co-escalated subcutaneously once-weekly with semaglutide every 2 weeks for the first 4 weeks, and every 4 weeks for the next 8 weeks until final target dose levels are reached.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of treatment-emergent adverse events (TEAEs) | Number of events | From time of dosing (day 1) to follow-up (week 24) | 
| Part 2: Change in body weight | Percentage | From randomisation (week 24) to end of treatment (week 40) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Change in body weight | kg | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Change in HbA1c | Percentage point | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Change in fasting plasma glucose | mmol/l | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Change in fasting insulin | pmol/l | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Change in waist circumference | cm | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in total cholesterol | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in HDL cholesterol | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in LDL cholesterol | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in VLDL cholesterol | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in Triglycerides | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Relative change in Free fatty acids | ratio to baseline | From randomisation (week 24) to end of treatment (week 40) | 
| Part 2: Number of emergent adverse events (TEAEs) | Count of events | From baseline at (week 0) to end of trial (week 48) | 
| Part 2: Number of serious treatment emergent adverse events (SAEs) | Count of events | From baseline at (week 0) to end of trial (week 48) |