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)

Type 2 Diabetes Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06269107
• Other study ID #: NN1535-4988
• Secondary ID: U1111-1283-86482
• Status: Recruiting
• Phase: Phase 3
• Start date: February 15, 2024
• Est. completion date: July 10, 2025

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 474
• Est. completion date: July 10, 2025
• Est. primary completion date: June 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Chongqing University Three Gorges Hospital	Chongqing	Chongqing
China	Harrison International Peace Hospital	Hengshui
China	Huizhou Central People's Hospital	Huizhou	Guangdong
China	Jinan Central Hospital	Jinan	Shandong
China	Jinan Central Hospital	Jinan	Shandong
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Shanghai Pudong New Area People's Hospital	Shanghai	Shanghai
China	The Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
Greece	"Laiko" General Hospital of Athens	Athens
Greece	'G. Gennimatas' General Hospital of Athens	Athens
Greece	Evangelismos Hospital	Athens
Greece	General Hospital of Kalamata	Kalamata
Greece	Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease	Larissa
Greece	"Thermi" Private Hosital	Thessaloniki
India	Ramaiah Memorial Hospital	Bangalore	Karnataka
India	Ramaiah Memorial Hospital	Bangalore	Karnataka
India	Post Graduate Institute of Medical Education & Research	Chandigarh
India	Madras Diabetes Research Foundation	Chennai	Tamil Nadu
India	Madras Diabetes Research Foundation	Chennai	Tamil Nadu
India	Diabetes, Thyroid and Endocrine Centre	Jaipur	Rajasthan
India	SMS Medical College & Hospital	Jaipur	Rajasthan
India	IPGME&R and SSKM Hospital	Kolkata
India	Udyaan Health Care	Lucknow	Uttar Pradesh
India	BSES MG hospital	Mumbai	Maharashtra
India	BSES MG hospital	Mumbai	Maharashtra
India	BYL Nair Hospital and T N Medical College Department of endo	Mumbai	Maharashtra
India	BYL Nair Hospital and T N Medical College Department of endo	Mumbai	Maharashtra
India	Seth GS Medical College & KEM Hospital	Mumbai	Maharashtra
India	Seth GS Medical College & KEM Hospital	Mumbai	Maharashtra
India	Mysore Medical College and Research Institute	Mysore	Karnataka
India	Chellaram Diabetes Institute	Pune	Maharashtra
Italy	I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani	Ancona
Italy	Casa della Salute di Ceccano (FR)	Ceccano (Frosinone)
Italy	ASL 4 Chiavarese	Chiavari (genova)
Italy	Ospedale San Salvatore, Dipartimento Medico ASL1 Abruzzo, UOC Diabetologia	L'Aquila	Abbruzzo
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Azienda Ospedaliera di Perugia;Ospedale S. Maria della Miser	Perugia
Italy	A.O.U. Policlinico Umberto I	Rome
Italy	Casa Sollievo della Sofferenza reparto endocrinologia	San Giovanni Rotondo	FG
Japan	Tokuyama clinic	Chiba
Japan	Oodouri Diabetes, Internal medicine Clinic	Hokkaido
Japan	Heiwadai Hospital	Miyazaki-shi	Miyazaki
Japan	Oyama East Clinic	Tochigi
Japan	Fukuwa Clinic	Tokyo
Japan	Juntendo University Hospital	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Tokyo
Poland	NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Malgorzata Arciszewska	Bialystok	Podlaskie
Poland	SNZOZ Lege Artis	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne Regionalne Centrum Diabetologii	Gdansk
Poland	Grazyna Pulka Specjalistyczny Osrodek "All-Med"	Krakow
Poland	Centrum Terapii Wspolczesnej	Lodz
Poland	Gabinet Lekarski Malgorzata Saryusz-Wolska	Lodz
Poland	Ko-Med Nova Sp.zo.o. Lublin II	Lublin
Poland	Ko-Med Nova Sp.zo.o. STASZOW	Staszow
Poland	NBR Polska Tomasz Klodawski	Warszawa
Poland	PANSTWOWY INSTYTUT MEDYCZNY MSWiA	Warszawa
Poland	Clinhouse Centrum Medyczne	Zabrze
Puerto Rico	Advanced Clinical Research LLC	Bayamon
South Africa	Langeberg Clinical Trials	Cape Town	Western Cape
South Africa	Dr Pillay's Rooms	Durban	KwaZulu-Natal
South Africa	Dr Pillay's Rooms	Durban	KwaZulu-Natal
South Africa	Dr R Dulabh	Johannesburg	Gauteng
South Africa	Dr R Dulabh	Johannesburg	Gauteng
South Africa	Newtown Clinical Research	Johannesburg	Gauteng
South Africa	Clinical Research Institute of South Africa	KwaDukuza	KwaZulu Natal
South Africa	Roodepoort Medicross Clinical Research Centre	Roodepoort	Gauteng
Turkey	Akdeniz University Tip Fakultesi Hastanesi	Antalya
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi - Endokrinoloji	Istanbul
Turkey	Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi	Istanbul
Turkey	T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Tekirdag Namik Kemal UTF	Tekirdag
United States	Albany Medical College - Endo	Albany	New York
United States	Albuquerque Clin Trials, Inc.	Albuquerque	New Mexico
United States	Amarillo Med Spec LLP	Amarillo	Texas
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	Elite Clinical Trials	Blackfoot	Idaho
United States	Wade Family Medicine	Bountiful	Utah
United States	Diab & Endo Assoc of Stark Co	Canton	Ohio
United States	Velocity Clinical Research- Cedar Park	Cedar Park	Texas
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	North Texas Endocrine Center	Dallas	Texas
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Northeast Research Institute	Fleming Island	Florida
United States	Diabetes and Thyroid Ctr of FW	Fort Worth	Texas
United States	Physician's East Endocrinology	Greenville	North Carolina
United States	Holston Medical Group	Kingsport	Tennessee
United States	Scripps Whittier Diabetes Inst	La Jolla	California
United States	Fmc Science, Llc	Lampasas	Texas
United States	First Valley Med Grp Lancaster	Lancaster	California
United States	Clinical Trials Research_Sacramento	Lincoln	California
United States	Advanced Medical Research	Maumee	Ohio
United States	Methodist Phys. Clinic	Omaha	Nebraska
United States	Desert Oasis Hlthcr Med Group	Palm Springs	California
United States	Endo Res Solutions Inc	Roswell	Georgia
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	NorthShore Univ Hlth Sys	Skokie	Illinois
United States	Cotton-O'Neil Diab & Endo Ctr	Topeka	Kansas
United States	New Venture Medical Research	Wadsworth	Ohio
United States	Southgate Medical Group, LLP	West Seneca	New York
United States	Clinical Research of Central Florida_Winter Haven	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  China,  Greece,  India,  Italy,  Japan,  Poland,  Puerto Rico,  South Africa,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glycated haemoglobin (HbA1c)	Measured in percentage (%)-point.	From baseline (week 0) to week 40
Secondary	Change in body weight	Measured in kilogram (kg).	From baseline (week 0) to week 40
Secondary	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
Secondary	Time spent less than (<) 3.0 mmol/L (54 mg/dL)	Measured in % of readings.	From week 36 to week 40
Secondary	Time spent greater than (>) 10.0 mmol/L (180 mg/dL)	Measured in % of readings.	From week 36 to week 40
Secondary	Weekly basal insulin dose	Measured in units of insulin.	From week 38 to week 40
Secondary	Change in fasting plasma glucose (FPG)	Measured in mmol/l.	From baseline (week 0) to week 40
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of severe hypoglycaemic episodes (level 3)	Measured in number of episodes.	From baseline (week 0) to week 45