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 Insulin Icodec (COMBINE 1)

• ClinicalTrials.gov Identifier: NCT05352815
• Recruitment Status: Completed
• First Posted: April 29, 2022
• Last Update Posted: May 1, 2024
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: April 24, 2022
• First Posted Date: April 29, 2022
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: June 1, 2022
• Actual Primary Completion Date: March 18, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2022)

Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline week 0 (V2) to week 52 (V54) ]

% point

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2022)

• Change in body weight [ Time Frame: From baseline week 0 (V2) to week 52 (V54) ]
  Kg
• 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) [ Time Frame: From baseline week 0 (V2) to week 57 (V56) ]
  Number of episodes

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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 Insulin Icodec
• Official Title: A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Insulin Icodec, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin.

Brief Summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin icodec 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 insulin icodec.

Participants will either get IcoSema or insulin icodec. Which treatment participants get is decided by chance. IcoSema and insulin icodec are both new medicines that doctors cannot prescribe.

Participants will get IcoSema or insulin icodec, which participants 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 21 clinic visits, 31 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.

Not applicable for China: Participants will be asked to wear a sensor that measures their blood sugar level all the time during a 5 week period at the end of the study.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: IcoSema
  Participants will receive once weekly IcoSema subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.
• Drug: Insulin icodec
  Participants will receive once weekly Insulin icodec subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.

Study Arms

• Experimental: IcoSema
  Intervention: Drug: IcoSema
• Active Comparator: Insulin icodec
  Intervention: Drug: Insulin icodec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 30, 2024): 1291
• Original Estimated Enrollment (submitted: April 24, 2022): 1290
• Actual Study Completion Date: April 23, 2024
• Actual Primary Completion Date: March 18, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key inclusion criteria

1. Male or female and age above or equal to 18 years at the time of signing informed consent.
2. Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
3. HbA1c of 7.0 10.0% (53.0 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

4. Treated with once daily or twice daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20- 80 units/day for 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. 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 (a)
   • Meglitinides (glinides) (a)
   • DPP 4 inhibitors (a)
   • Sodium glucose co transporter 2 inhibitors
   • Alpha glucosidase inhibitors
   • Thiazolidinediones
   • Marketed oral combination products only including the products listed above.
5. Body mass index (BMI) below or equal to 40.0 kg/m^2. (a) Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation.

Key exclusion criteria

1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
2. 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).
3. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
4. Any episodes (as declared by the participant or in the medical records.) of diabetic ketoacidosis within 90 days before screening.
5. Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
6. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
7. Chronic heart failure classified as being in New York Heart Association Class IV at screening.
8. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
9. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Bulgaria, China, Croatia, Finland, India, Italy, Japan, Korea, Republic of, Mexico, Norway, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, South Africa, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT05352815
• Other Study ID Numbers: NN1535-4591; U1111 1260 8259 ( Other Identifier: World Health Organization (WHO) ); 2020 005281 34 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Transparency (dept. 2834); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: April 2024