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 Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

• ClinicalTrials.gov Identifier: NCT05013229
• Recruitment Status: Completed
• First Posted: August 19, 2021
• Last Update Posted: February 23, 2024
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: August 13, 2021
• First Posted Date: August 19, 2021
• Last Update Posted Date: February 23, 2024
• Actual Study Start Date: November 30, 2021
• Actual Primary Completion Date: November 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2021)

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

Percent-points

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 13, 2021)

• Change in body weight [ Time Frame: From baseline week 0 (V2) to week 52 (V54) ]
  Kg
• Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) [ Time Frame: From week 0 (V52) to week 52 (V54) ]
  Number of episodes
• Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V50) to week 52 (V54) ]
  Percentage of readings
• Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V50) to week 52 (V54) ]
  Percentage of readings
• Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V50) to week 52 (V54) ]
  Percentage of readings
• Change in fasting plasma glucose (FPG) [ Time Frame: From baseline week 0 (V2) to week 52 (V54) ]
  mmol/L
• Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction [ Time Frame: From baseline week 0 (V2) to week 52 (V54) ]
  Score 0-36. The higher the score the greater the satisfaction with treatment.
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 57 (V56) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) [ Time Frame: From baseline week 0 (V2) to week 57 (V56) ]
  Number of episodes
• Weekly insulin dose (total) [ Time Frame: From week 50 (V52) to week 52 (V54) ]
  Units

• 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 Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)
• Official Title: A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL Combined With Insulin Aspart, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin. COMBINE 3

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 glargine taken daily with insulin aspart 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 glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries.

Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines 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 be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study.

Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

• 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 a once weekly subcutanous (s.c.) injection of IcoSema, on the same day every week for 52 weeks.
• Drug: Insulin glargine
  Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.
• Drug: insulin aspart
  Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.

Study Arms

• Experimental: IcoSema
  Participants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period.
  Intervention: Drug: IcoSema
• Active Comparator: Insuling glargine/insulin aspart
  Participants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.
  Interventions:

  • Drug: Insulin glargine
  • Drug: insulin aspart

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 29, 2023): 679
• Original Estimated Enrollment (submitted: August 13, 2021): 680
• Actual Study Completion Date: November 14, 2023
• Actual Primary Completion Date: November 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female and age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
• HbA1c of 7.0-10.0 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

• 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 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 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.

• Body mass index (BMI) less than or equal to 40.0 kg/m^2.

  1. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.

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.
• 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).
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
• Any episodes of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records.
• Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
• Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at screening.
• Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
• 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: Czechia, France, Germany, Hungary, India, Italy, Japan, Malaysia, Poland, Slovenia, South Africa, Thailand, Turkey, United States

Administrative Information

• NCT Number: NCT05013229
• Other Study ID Numbers: NN1535-4593; U1111-1260-8295 ( Other Identifier: WHO ); 2020-005309-18 ( EudraCT Number ); jRCT2051210127 ( Registry Identifier: JAPIC )
• 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: Not Provided
• 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. 1452); Novo Nordisk A/S

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