A Research Study to See How Well New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Levels in People With Type 2 Diabetes (T2D), Compared to Daily Insulin Glargine (COMBINE 4) (COMBINE 4)

• ClinicalTrials.gov Identifier: NCT06269107
• Recruitment Status: Recruiting
• First Posted: February 21, 2024
• Last Update Posted: April 18, 2024
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: February 13, 2024
• First Posted Date: February 21, 2024
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: February 15, 2024
• Estimated Primary Completion Date: June 5, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2024)

Change in glycated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to week 40 ]

Measured in percentage (%)-point.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 13, 2024)

• Change in body weight [ Time Frame: From baseline (week 0) to week 40 ]
  Measured in kilogram (kg).
• Time in range 3.9-10.0 millimoles per liter (mmol/L) (70-180 milligram per deciliter [mg/dL]) [ Time Frame: From week 36 to week 40 ]
  Measured in % of readings.
• Time spent less than (<) 3.0 mmol/L (54 mg/dL) [ Time Frame: From week 36 to week 40 ]
  Measured in % of readings.
• Time spent greater than (>) 10.0 mmol/L (180 mg/dL) [ Time Frame: From week 36 to week 40 ]
  Measured in % of readings.
• Weekly basal insulin dose [ Time Frame: From week 38 to week 40 ]
  Measured in units of insulin.
• Change in fasting plasma glucose (FPG) [ Time Frame: From baseline (week 0) to week 40 ]
  Measured in mmol/l.
• Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction [ Time Frame: From baseline (week 0) to week 40 ]
  The DTSQs items are scored on a 7-point graded response scale ranging from 0 to 6. Score ranges from 0 to 36. Higher scores indicate greater the satisfaction with medication.
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by blood glucose meter) or severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline (week 0) to week 45 ]
  Measured in number of episodes.
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) [ Time Frame: From baseline (week 0) to week 45 ]
  Measured in number of episodes.
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline (week 0) to week 45 ]
  Measured in 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 New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Levels in People With Type 2 Diabetes (T2D), Compared to Daily Insulin Glargine (COMBINE 4)
• Official Title: A 40-week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL in Participants With Type 2 Diabetes Inadequately Controlled on Oral Anti Diabetic Drugs COMBINE 4
• 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 (mentioned as insulin glargine in this form) taken daily in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar levels as compared to insulin glargine in people with type 2 diabetes who do not have their blood sugar properly controlled with other oral diabetes medicines. Participant will either get IcoSema or insulin glargine. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine in many countries. The study will last for about 11 months (47 weeks).
• 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: Type 2 Diabetes

Intervention

• Drug: IcoSema
  IcoSema will be administered subcutaneously.
• Drug: Insulin glargine
  Insulin glargine will be administered subcutaneously.

Study Arms

• Experimental: IcoSema
  Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.
  Intervention: Drug: IcoSema
• Experimental: Insulin glargine
  Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.
  Intervention: Drug: Insulin glargine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2024): 474
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 10, 2025
• Estimated Primary Completion Date: June 5, 2025 (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 the informed consent.
• Diagnosed with T2D greater than or equal to (≥) 180 days before screening.
• HbA1c ≥ 8.0% (≥ 64.0 millimoles per mole [mmol/mol]) as assessed by central laboratory on the day of screening.
• Insulin naïve. Short term insulin treatment for a maximum of 14 consecutive days before screening is allowed, as is prior insulin treatment for gestational diabetes.

• Currently treated with 1-3 oral anti diabetic drug (OADs) with stable daily doses ≥ 90 days before screening comprising any of the following anti diabetic drug(s) at effective or maximum tolerated dose.

  • Metformin
  • Sulfonylureas
  • Meglitinides (glinides)
  • Dipeptidyl peptidase (DPP) 4 inhibitors
  • 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 kilogram per square meter (kg/m^2).

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbaring potential and not using 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).
• Any episodes of diabetic ketoacidosis or treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
• 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: Novo Nordisk; (+1) 866-867-7178; clinicaltrials@novonordisk.com

• Listed Location Countries: China, Greece, India, Italy, Japan, Poland, Puerto Rico, South Africa, Turkey, United States

Administrative Information

• NCT Number: NCT06269107
• Other Study ID Numbers: NN1535-4988; U1111-1283-8648 ( Other Identifier: World Health Organization (WHO) ); 2022-502484-38-00 ( Other Identifier: European Medicines Agency (EMA) )
• 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