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)

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05013229
• Other study ID #: NN1535-4593
• Secondary ID: U1111-1260-82952
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2021
• Est. completion date: November 14, 2023

Study information

• Verified date: February 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 679
• Est. completion date: November 14, 2023
• Est. primary completion date: November 14, 2023
• 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 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Czechia	University Hospital U sv. Anny	Brno
Czechia	University Hospital U sv. Anny	Brno
Czechia	FN Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Plzen	Plzen	Czech Republic
Czechia	Fledip s.r.o.	Praha
Czechia	III. interni klinika VFN a 1. LK UK v Praze	Praha
Czechia	Institut klinicke a experimentalni mediciny_Praha	Praha
Czechia	Diabet2 s.r.o.	Praha 1
Czechia	Diabetologická a interní ambulance Diabet2	Praha 1
Czechia	Fledip s.r.o.	Praha 6
Czechia	ResTrial s.r.o.	Praha 8
France	Centre Hospitalier Departemental Vendee- La Roche Sur Yon	LA ROCHE-sur-YON cedex 9
France	Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2	Le Creusot
France	Aphp-Hopital Lariboisiere-1	Paris
France	Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2	Pessac
France	Groupe Hospitalier Mutualiste Des Portes Du Sud	Venissieux
Germany	InnoDiab Forschung GmbH	Essen
Germany	Wendisch/Dahl Hamburg	Hamburg
Germany	Institut für Diabetesforschung GmbH Münster - Dr. med. Rose	Münster
Germany	RED-Institut für medizinische Forschung und Fortbildung GmbH	Oldenburg in Holstein
Germany	Zentrum für klinische Studien Alexander Segner	Saint Ingbert-Oberwürzbach
Hungary	Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház	Békéscsaba
Hungary	ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.	Budapest
Hungary	Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.	Budapest
Hungary	Semmelweis Egyetem II. Belgyógyászati Klinika	Budapest
Hungary	Szocs Depot Egészségügyi Szolgáltató Kft.	Budapest
India	Apollo Hospital, Ahmedabad	Ahmedabad	Gujarat
India	Swasthya Diabetes Care	Ahmedabad
India	Diacon Hospital Private Limited	Bangalore	Karnataka
India	Post Graduate Institute of Medical Education & Research	Chandigarh	Punjab
India	Madras Diabetes Research Foundation	Chennai	Tamil Nadu
India	Apollo Hospital International Ltd	Gandhinagar	Gujarat
India	TOTALL Diabetes Hormone Institute	Indore	Madhya Pradesh
India	Diabetes, Thyroid and Endocrine Centre	Jaipur	Rajasthan
India	Medanta Lucknow Hospital	Lucknow	Uttar Pradesh
India	Christian Medical College and Hospital	Ludhiana	Punjab
India	Fortis Heart Institute and Multispeciality Hospital	Mohali	Punjab
India	chelleram Diabetes Institute	Pune	Maharashtra
India	Sahyadri Speciality Hospital	Pune	Maharashtra
India	Sahyadri Super Speciality Hospital	Pune	Maharashtra
India	Christian Medical College Hospital, Vellore	Vellore	Tamil Nadu
Italy	Azienda Ospedaliero-Universitaria Renato Dulbecco	Catanzaro	CZ
Italy	Azienda Ospedaliera Luigi Sacco	Milano
Italy	Ospedale Civico Partinico di Palermo	Partinico
Italy	Pol. Uni. Campus Biomedico UOC Endocrinologia e Diabetologia	Roma	RM
Italy	IRCCS Multimedica	Sesto San Giovanni (MI)
Japan	TOSAKI Clinic for Diabetes and Endocrinology_Diabetes and Endocrinology	Aichi
Japan	Akaicho Clinic	Chiba-shi, Chiba
Japan	The Institute of Medical Science, Asahi Life Foundation	Chuo-ku, Tokyo
Japan	Naka Kinen Clinic	Ibaraki
Japan	Asano Clinic	Kawagoe-shi	Saitama, Japan
Japan	Minami Akatsuka Clinic	Mito-shi, Ibaraki
Japan	Heiwadai Hospital	Miyazaki-shi	Miyazaki
Japan	Takatsuki Red Cross Hospital	Osaka
Japan	Tokyo Medical Univ. Hospital_Diabetes, Metabolism and Endocrinology	Shinjuku-ku, Tokyo
Japan	Fukuwa Clinic	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Tokyo
Malaysia	Klinik Kesihatan Simpang Kuala	Alor Setar
Malaysia	Hospital Universiti Kebangsaan Malaysia	Cheras	Kuala Lumpur
Malaysia	Hospital Universiti Sains Malaysia_Kota Bharu, Kelantan	Kota Bharu	Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Malaysia	Miri Hospital	Miri, Sarawak
Malaysia	Hospital Seri Manjung	Seri Manjung	Perak
Malaysia	University Technology MARA (UiTM) - Puncak Alam	Sungai Buloh	Selangor
Poland	NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Malgorzata Arciszewska	Bialystok	Podlaskie
Poland	SNZOZ Lege Artis	Bialystok
Poland	Centrum Medyczne Pratia Gdynia	Gdynia	Pomorskie
Poland	Centrum Terapii Wspolczesnej	Lodz
Poland	Gabinet Lekarski Malgorzata Saryusz-Wolska	Lodz
Poland	NBR Polska Tomasz Klodawski	Warszawa
Slovenia	Healthcare centre Kocevje	Kocevje
Slovenia	Healthcare Centre Koper	Koper
Slovenia	UKC Ljubljana, Endocrinology and Diabetes	Ljubljana
Slovenia	General Hospital Murska Sobota	Murska Sobota
Slovenia	General Hospital Nova Gorica_Diabetes	Nova Gorica
South Africa	Medi-Clinic Bloemfontein	Bloemfontein	Free State
South Africa	Spoke Research Inc	Cape Town	Western Cape
South Africa	Lenasia Clinical Trial Centre	Lenasia	Gauteng
South Africa	Prof P. Joshi	Pretoria	Gauteng
Thailand	Rajavithi Hospital	Bangkok
Thailand	Siriraj Hospital_Bangkoknoi, Bangkok	Bangkoknoi, Bangkok	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai	Mueang Chiang Mai District
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Maharat Nakhon Ratchasima Hospital	Nakhon Ratchasima
Turkey	Baskent Universitesi Adana	Adana
Turkey	Gulhane Egitim Arastirma Hastanesi	Ankara
Turkey	Akdeniz University Tip Fakultesi Hastanesi	Antalya
Turkey	Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi	Aydin
Turkey	Pamukkale Universitesi Tip Fakultesi	Denizli
Turkey	TC SB Ist.Il Sag.Müd.Prof.Dr.Cemil Tascioglu Sehir Hastanesi	Istanbul
Turkey	Dokuz Eylul University Medical Faculty	Izmir
United States	Amarillo Med Spec LLP	Amarillo	Texas
United States	AM Diabetes And Endocrinology Center	Bartlett	Tennessee
United States	Northern Pines Hlth Ctr, PC	Buckley	Michigan
United States	Diab & Endo Assoc of Stark Co	Canton	Ohio
United States	Univ Diab & Endo Consultants	Chattanooga	Tennessee
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Creekside Endocrine Associates	Denver	Colorado
United States	Northeast Research Institute	Fleming Island	Florida
United States	Prestige Clinical Research	Franklin	Ohio
United States	PlanIt Research, PLLC	Houston	Texas
United States	Protenium Clinical Research	Hurst	Texas
United States	MedStar Hlth Res Institute	Hyattsville	Maryland
United States	Northeast Res Inst. Inc.	Jacksonville	Florida
United States	Scripps Wht Diab Inst La Jolla	La Jolla	California
United States	Milton Haber, M.D.	Laredo	Texas
United States	Palm Research Center Inc-Vegas	Las Vegas	Nevada
United States	The Research Group of Lexington LLC	Lexington	Kentucky
United States	Downtown LA Res Ctr. Inc.	Los Angeles	California
United States	South Broward Research LLC	Miramar	Florida
United States	HealthStar Physicians PC	Morristown	Tennessee
United States	Adult Medicine of Lake County, Inc.	Mount Dora	Florida
United States	Saltzer Medical Group Research	Nampa	Idaho
United States	Southern NH Diabetes and Endocrinology	Nashua	New Hampshire
United States	Florida Inst For Clin Res	Orlando	Florida
United States	Clinical Investigations Of Texas	Plano	Texas
United States	Rainier Clin Res Ctr Inc	Renton	Washington
United States	Endo Res Solutions Inc	Roswell	Georgia
United States	Chrysalis Clinical Research	Saint George	Utah
United States	Briggs Clinical Research, LLC	San Antonio	Texas
United States	NE Clin Res of San Antonio	San Antonio	Texas
United States	San Diego Family Care	San Diego	California
United States	Hillcrest Clinical Research	Simpsonville	South Carolina
United States	NorthShore Univ Hlth Sys	Skokie	Illinois
United States	Piedmont Healthcare/Research	Statesville	North Carolina
United States	Simcare Medical Research, LLC	Sugar Land	Texas
United States	New Venture Medical Research	Wadsworth	Ohio
United States	Iowa Diab & Endo Res Center	West Des Moines	Iowa
United States	Southgate Medical Group, LLP	West Seneca	New York
United States	Accellacare	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Malaysia,  Poland,  Slovenia,  South Africa,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	Percent-points	From baseline week 0 (V2) to week 52 (V54)
Secondary	Change in body weight	Kg	From baseline week 0 (V2) to week 52 (V54)
Secondary	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)	Number of episodes	From week 0 (V52) to week 52 (V54)
Secondary	Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Secondary	Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Secondary	Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Secondary	Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 52 (V54)
Secondary	Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction	Score 0-36. The higher the score the greater the satisfaction with treatment.	From baseline week 0 (V2) to week 52 (V54)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)
Secondary	Weekly insulin dose (total)	Units	From week 50 (V52) to week 52 (V54)