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)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: IcoSema; Drug: Insulin glargine

• Study Type: Interventional
• Enrollment (Estimated): 474
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• China
  • Hengshui, China, 053000
    • Withdrawn
    • Harrison International Peace Hospital
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 404000
      • Recruiting
      • Chongqing University Three Gorges Hospital
  • Guangdong
    • Huizhou, Guangdong, China, 516001
      • Recruiting
      • Huizhou Central People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210011
      • Recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
    • Zhenjiang, Jiangsu, China, 212001
      • Recruiting
      • The Affiliated Hospital of Jiangsu University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Not yet recruiting
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250013
      • Recruiting
      • Jinan Central Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 201200
      • Recruiting
      • Shanghai Pudong New Area People's Hospital
• Greece
  • Athens, Greece, GR-11527
    • Recruiting
    • "Laiko" General Hospital of Athens
  • Athens, Greece, GR-10676
    • Recruiting
    • Evangelismos Hospital
  • Athens, Greece, GR-115 27
    • Recruiting
    • 'G. Gennimatas' General Hospital of Athens
  • Kalamata, Greece, 24100
    • Recruiting
    • General Hospital of Kalamata
  • Larissa, Greece, GR-41110
    • Recruiting
    • Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease
  • Thessaloniki, Greece, GR-57001
    • Recruiting
    • "Thermi" Private Hosital
• India
  • Chandigarh, India, 160012
    • Not yet recruiting
    • Post Graduate Institute of Medical Education & Research
  • Kolkata, India, 700020
    • Not yet recruiting
    • IPGME&R and SSKM Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Not yet recruiting
      • Ramaiah Memorial Hospital
    • Bangalore, Karnataka, India, 560054
      • Recruiting
      • Ramaiah Memorial Hospital
    • Mysore, Karnataka, India, 570001
      • Not yet recruiting
      • Mysore Medical College and Research Institute
  • Maharashtra
    • Mumbai, Maharashtra, India, 400058
      • Not yet recruiting
      • BSES MG hospital
    • Mumbai, Maharashtra, India, 400058
      • Recruiting
      • BSES MG hospital
    • Mumbai, Maharashtra, India, 400012
      • Not yet recruiting
      • Seth GS Medical College & KEM Hospital
    • Mumbai, Maharashtra, India, 400008
      • Not yet recruiting
      • BYL Nair Hospital and T N Medical College Department of endo
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Seth GS Medical College & KEM Hospital
    • Mumbai, Maharashtra, India, 400008
      • Recruiting
      • BYL Nair Hospital and T N Medical College Department of endo
    • Pune, Maharashtra, India, 411021
      • Recruiting
      • Chellaram Diabetes Institute
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Not yet recruiting
      • SMS Medical College & Hospital
    • Jaipur, Rajasthan, India, 302006
      • Recruiting
      • Diabetes, Thyroid and Endocrine Centre
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Not yet recruiting
      • Madras Diabetes Research Foundation
    • Chennai, Tamil Nadu, India, 600086
      • Recruiting
      • Madras Diabetes Research Foundation
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226002
      • Recruiting
      • Udyaan Health Care
• Italy
  • Ancona, Italy, 60127
    • Not yet recruiting
    • I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani
  • Ceccano (Frosinone), Italy, 03023
    • Recruiting
    • Casa della Salute di Ceccano (FR)
  • Chiavari (genova), Italy, 16034
    • Not yet recruiting
    • ASL 4 Chiavarese
  • Milano, Italy, 20162
    • Recruiting
    • Asst Grande Ospedale Metropolitano Niguarda
  • Perugia, Italy, 06129
    • Recruiting
    • Azienda Ospedaliera di Perugia;Ospedale S. Maria della Miser
  • Rome, Italy, 00161
    • Recruiting
    • A.O.U. Policlinico Umberto I
  • Abbruzzo
    • L'Aquila, Abbruzzo, Italy, 67100
      • Recruiting
      • Ospedale San Salvatore, Dipartimento Medico ASL1 Abruzzo, UOC Diabetologia
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Recruiting
      • Casa Sollievo della Sofferenza reparto endocrinologia
• Japan
  • Chiba, Japan, 261-0004
    • Recruiting
    • Tokuyama clinic
  • Hokkaido, Japan, 060-0001
    • Recruiting
    • Oodouri Diabetes, Internal medicine Clinic
  • Tochigi, Japan, 323-0022
    • Recruiting
    • Oyama East Clinic
  • Tokyo, Japan, 113-8431
    • Recruiting
    • Juntendo University Hospital
  • Tokyo, Japan, 103-0027
    • Recruiting
    • Tokyo-Eki Center-building Clinic
  • Tokyo, Japan, 104-0031
    • Recruiting
    • Fukuwa Clinic
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 880-0034
      • Recruiting
      • Heiwadai Hospital
• Poland
  • Bialystok, Poland, 15-404
    • Recruiting
    • SNZOZ Lege Artis
  • Gdansk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne Regionalne Centrum Diabetologii
  • Krakow, Poland, 30-033
    • Recruiting
    • Grazyna Pulka Specjalistyczny Osrodek "All-Med"
  • Lodz, Poland, 90-338
    • Recruiting
    • Centrum Terapii Wspolczesnej
  • Lodz, Poland, 90-132
    • Recruiting
    • Gabinet Lekarski Malgorzata Saryusz-Wolska
  • Lublin, Poland, 20-362
    • Recruiting
    • Ko-Med Nova Sp.zo.o. Lublin II
  • Staszow, Poland, 28-200
    • Recruiting
    • Ko-Med Nova Sp.zo.o. STASZOW
  • Warszawa, Poland, 00-710
    • Recruiting
    • NBR Polska Tomasz Klodawski
  • Warszawa, Poland, 02-507
    • Recruiting
    • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
  • Zabrze, Poland, 41-807
    • Recruiting
    • Clinhouse Centrum Medyczne
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-435
      • Recruiting
      • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Recruiting
    • Advanced Clinical Research LLC
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Recruiting
      • Newtown Clinical Research
    • Johannesburg, Gauteng, South Africa, 1812
      • Recruiting
      • Dr R Dulabh
    • Johannesburg, Gauteng, South Africa, 1812
      • Not yet recruiting
      • Dr R Dulabh
    • Roodepoort, Gauteng, South Africa, 1724
      • Recruiting
      • Roodepoort Medicross Clinical Research Centre
  • KwaZulu Natal
    • KwaDukuza, KwaZulu Natal, South Africa, 4449
      • Recruiting
      • Clinical Research Institute of South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4450
      • Not yet recruiting
      • Dr Pillay's Rooms
    • Durban, KwaZulu-Natal, South Africa, 4450
      • Recruiting
      • Dr Pillay's Rooms
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7572
      • Recruiting
      • Langeberg Clinical Trials
• Turkey
  • Antalya, Turkey, 07058
    • Recruiting
    • Akdeniz University Tip Fakultesi Hastanesi
  • Istanbul, Turkey, 34371
    • Recruiting
    • Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey, 34390
    • Recruiting
    • Istanbul Universitesi Istanbul Tip Fakultesi - Endokrinoloji
  • Istanbul, Turkey, 34899
    • Recruiting
    • T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi
  • Tekirdag, Turkey, 59030
    • Recruiting
    • Tekirdag Namık Kemal UTF
• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Scripps Whittier Diabetes Inst
    • Lancaster, California, United States, 93534
      • Recruiting
      • First Valley Med Grp Lancaster
    • Lincoln, California, United States, 95648
      • Recruiting
      • Clinical Trials Research_Sacramento
    • Palm Springs, California, United States, 92262
      • Recruiting
      • Desert Oasis Hlthcr Med Group
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Recruiting
      • Northeast Research Institute
    • Winter Haven, Florida, United States, 33880
      • Recruiting
      • Clinical Research of Central Florida_Winter Haven
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Atlanta Diabetes Associates
    • Roswell, Georgia, United States, 30076
      • Recruiting
      • Endo Res Solutions Inc
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Recruiting
      • Elite Clinical Trials
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Recruiting
      • Cedar-Crosse Research Center
    • Skokie, Illinois, United States, 60077
      • Recruiting
      • NorthShore Univ Hlth Sys
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Recruiting
      • Cotton-O'Neil Diab & Endo Ctr
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Recruiting
      • Methodist Phys. Clinic
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Recruiting
      • Albuquerque Clin Trials, Inc.
  • New York
    • Albany, New York, United States, 12206
      • Recruiting
      • Albany Medical College - Endo
    • West Seneca, New York, United States, 14224
      • Recruiting
      • Southgate Medical Group, LLP
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • Physician's East Endocrinology
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Diab & Endo Assoc of Stark Co
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Advanced Medical Research
    • Wadsworth, Ohio, United States, 44281-9236
      • Recruiting
      • New Venture Medical Research
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Recruiting
      • Holston Medical Group
  • Texas
    • Amarillo, Texas, United States, 79106
      • Recruiting
      • Amarillo Med Spec LLP
    • Cedar Park, Texas, United States, 78613
      • Recruiting
      • Velocity Clinical Research- Cedar Park
    • Dallas, Texas, United States, 75231
      • Recruiting
      • North Texas Endocrine Center
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Velocity Clinical Res-Dallas
    • Fort Worth, Texas, United States, 76132
      • Recruiting
      • Diabetes and Thyroid Ctr of FW
    • Lampasas, Texas, United States, 76550
      • Recruiting
      • Fmc Science, Llc
    • Shavano Park, Texas, United States, 78231
      • Recruiting
      • Consano Clinical Research, LLC
  • Utah
    • Bountiful, Utah, United States, 84010
      • Recruiting
      • Wade Family Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IcoSema; Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.	Drug: IcoSema; IcoSema will be administered subcutaneously.
Experimental: Insulin glargine; Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.	Drug: Insulin glargine; Insulin glargine will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycated haemoglobin (HbA1c)	Measured in percentage (%)-point.	From baseline (week 0) to week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Measured in kilogram (kg).	From baseline (week 0) to week 40
Time in range 3.9-10.0 millimoles per liter (mmol/L) (70-180 milligram per deciliter [mg/dL])	Measured in % of readings.	From week 36 to week 40
Time spent less than (<) 3.0 mmol/L (54 mg/dL)	Measured in % of readings.	From week 36 to week 40
Time spent greater than (>) 10.0 mmol/L (180 mg/dL)	Measured in % of readings.	From week 36 to week 40
Weekly basal insulin dose	Measured in units of insulin.	From week 38 to week 40
Change in fasting plasma glucose (FPG)	Measured in mmol/l.	From baseline (week 0) to week 40
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction	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.	From baseline (week 0) to week 40
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)	Measured in number of episodes.	From baseline (week 0) to week 45
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)	Measured in number of episodes.	From baseline (week 0) to week 45
Number of severe hypoglycaemic episodes (level 3)	Measured in number of episodes.	From baseline (week 0) to week 45

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): June 5, 2025
• Study Completion (Estimated): July 10, 2025

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• 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))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No