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 Weekly Insulin Icodec

Diabetes Mellitus, Type 2 Clinical Trial

— COMBINE 1  

Official title:

A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Insulin Icodec, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05352815
• Other study ID #: NN1535-4591
• Secondary ID: U1111 1260 82592
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2022
• Est. completion date: April 23, 2024

Study information

• Verified date: April 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 icodec taken once a week 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 icodec. Participants will either get IcoSema or insulin icodec. Which treatment participants get is decided by chance. IcoSema and insulin icodec are both new medicines that doctors cannot prescribe. Participants will get IcoSema or insulin icodec, which participants must inject once a week 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 have 21 clinic visits, 31 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period. Not applicable for China: Participants will be asked to wear a sensor that measures their blood sugar level all the time during a 5 week period at the end of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1291
• Est. completion date: April 23, 2024
• Est. primary completion date: March 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key inclusion criteria

1. Male or female and age above or equal to 18 years at the time of signing informed consent.

2. Diagnosed with type 2 diabetes mellitus 180 days or more before screening.

3. HbA1c of 7.0 10.0% (53.0 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

4. 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 for 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 for 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.

5. Body mass index (BMI) below or equal to 40.0 kg/m^2. (a) Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation. Key exclusion criteria

1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.

2. 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).

3. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.

4. Any episodes (as declared by the participant or in the medical records.) of diabetic ketoacidosis within 90 days before screening.

5. Presence or history of pancreatitis (acute or chronic) within 180 days before screening.

6. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.

7. Chronic heart failure classified as being in New York Heart Association Class IV at screening.

8. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.

9. 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 once weekly IcoSema subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.
• Insulin icodec
Participants will receive once weekly Insulin icodec subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.

Locations

Country	Name	City	State
Australia	Holdsworth House Clinical Research	Darlinghurst	New South Wales
Australia	Barwon Health (The Geelong Hospital)	Geelong	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Novatrials	Kotara	New South Wales
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Southern Adelaide Diabetes & Endocrine Services	Oaklands Park	South Australia
Australia	Illawarra Diabetes Service Clinical Trials & Research Unit	Wollongong	New South Wales
Belgium	Imeldaziekenhuis - Bonheiden - Department of Endocrinology	Bonheiden
Belgium	Universitair Ziekenhuis Brussel - Diabeteskliniek	Brussel
Belgium	Cliniques Universitaires Saint-Luc - Serv Endocrinologie - Diabétologie	Bruxelles
Belgium	UZA - UZ Antwerpen - Department of Endocrinology	Edegem
Belgium	AZ Groeninge - Kortrijk - Centrum Endo - Diabetologie	Kortrijk
Belgium	UZ Leuven - Endocrinology	Leuven
Bulgaria	"IPSMC - d-r Nikolay Kostadinov" EOOD	Burgas
Bulgaria	'Medical center Medi city 21' OOD	Kyustendil
Bulgaria	DCC I- Pleven EOOD	Pleven
Bulgaria	UMHAT "Kaspela", Depart. Endocrinology and Metab. Diseases	Plovdiv
Bulgaria	MMA-MHAT Sofia, Clinic of Endocrinology and Metab. Diseases	Sofia
China	Peking University People's Hospital	Beijing	Beijing
China	Changzhou No.2 People's Hospital, Yanghu Branch	Changzhou	Jiangsu
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	Chongqing University Three Gorges Hospital	ChongQing	Chongqing
China	Anhui Provincial Hospital	Hefei	Anhui
China	Harrison International Peace Hospital	Hengshui	Hebei
China	Huizhou Central People's Hospital	Huizhou	Guangdong
China	Jinan Central Hospital	Ji'nan	Shandong
China	Huaihe Hospital of Henan University	Kaifeng	Henan
China	The Second Affiliated Hospital of Nanjing Medical University_Nanjing	Nanjing	Jiangsu
China	Shanghai Fifth People's Hospital	Shanghai	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	General Hospital of Tianjin Medical University	Tianjin	Tianjin
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	The Affiliated Hospital of Jiangsu University_Zhenjiang	Zhenjiang	Jiangsu
Croatia	Klinicki bolnicki centar Osijek	Osijek
Croatia	Poliklinika SLAVONIJA OSIJEK	Osijek	Osjecko - Baranjska Županija
Croatia	Opca bolnica Pula	Pula
Croatia	KBC Rijeka, Endokrinologija	Rijeka
Croatia	Poliklinika Solmed	Zagreb	Grad Zagreb
Finland	Ähtärin terveysasema	Ähtäri
Finland	Health Step Finland Oy	Kuopio
Finland	Raision sosiaali- ja terveyskeskus	Raisio
Finland	Tampereen diabetesvastaanotto	Tampere
Finland	Turku University Hospital	Turku
India	Gujarat Endocrine Centre	Ahmedabad	Gujarat
India	Post Graduate Institute of Medical Education & Research	Chandigarh	Punjab
India	M.V.Hospital for Diabetes Pvt. Ltd.	Chennai	Tamil Nadu
India	S.C.B. Medical College	Cuttack	Orissa
India	Osmania General Hospital	Hyderabad	Telengana
India	Ramdev Rao Hospital	Hyderabad	Telangana
India	TOTALL Diabetes Hormone Institute	Indore	Madhya Pradesh
India	Excel Endocrine Centre	Kolhapur	Maharashtra
India	Government Medical College, Kozhikode	Kozhikode	Kerala
India	Dayanand Medical College & Hospital_Ludhiana	Ludhiana	Punjab
India	Arthur Asirvatham hospital,	Madurai	Tamil Nadu
India	BYL Nair Hospital and T N Medical College Department of endo	Mumbai	Maharashtra
India	Seth GS medical college and KEM Hospital	Mumbai	Maharashtra
India	Lady Hardinge Medical College	New Delhi
India	Jothydev's Diabetes & Research Center	Thriruvananthapuram	Kerala
Italy	A.O.U. Consorziale Policlinico di Bari	Bari	BA
Italy	Policlinico Mater Domini Università di Catanzaro	Catanzaro
Italy	ASL 4 Chiavarese	Chiavari (genova)
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Japan	Kumanomae Nishimura Internal Medical Clinic	Arakawa-ku, Tokyo
Japan	Akaicho Clinic	Chiba-shi, Chiba
Japan	Hayashi Diabetes Clinic	Chigasaki-shi	Kanagawa, Japan
Japan	Hayashi Diabetes Clinic	Chigasaki-shi, Kanagawa	Kanagawa, Japan
Japan	Futata Tetsuhiro Clinic Meinohama	Fukuoka-shi, Fukuoka
Japan	Kunisaki Makoto Clinic	Fukuoka-shi, Fukuoka
Japan	Sasaki Hospital Internal Medicine	Hokkaido
Japan	Seino Internal Medicine Clinic	Koriyama-shi	Fukushima, Japan
Japan	Yoshimura clinic	Kumamoto
Japan	Jinnouchi Hospital	Kumamoto-shi	Kumamoto, Japan
Japan	Heiwadai Hospital	Miyazaki-shi	Miyazaki
Japan	Hisatomi Clinic	Saga-shi, Saga
Japan	Manda Memorial Hospital	Sapporo-shi, Hokkaido	Hokkaido, Japan
Japan	Fukuwa Clinic	Tokyo
Japan	Tokyo-Eki Center-building Clinic	Tokyo
Japan	Yokohama City University Hospital, Endocrinology, Metabolism	Yokohama-shi, Kanagawa
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do
Korea, Republic of	Soonchunhyang University Hospital	Cheonan	Chungcheongnam-do
Korea, Republic of	Seoul National University Bundang Hospital_Seongnam-si	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Nowon Eulji Medical Center, Eulji University	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Wonju Severance Christian Hospital	Wonju
Mexico	Centro de Investigación Cardiometabólica de Aguascalientes	Aguascalientes
Mexico	Clínicos Asociados BOCM, S.C.	Mexico City
Mexico	Hospital Universitario Dr. José Eleuterio González_Monterrey	Monterrey	Nuevo León
Norway	Nordlandssykehuset Bodø	Bodø
Norway	Drammen sykehus - Vestre Viken HF	Drammen
Norway	Sykehuset Innlandet HF Hamar	Hamar
Norway	Oslo universitetssykehus Aker	Oslo
Norway	St. Olavs Hospital HF	Trondheim
Poland	Uniwersyteckie Centrum Kliniczne (UCK)	Gdansk
Poland	NZOZ "CenterMed Lublin" Sp. z o.o.	Lublin
Poland	NZOZ Przychodnia Specjalistyczna Medica	Lublin	Lubelski
Poland	Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji	Warszawa
Portugal	Hospital Garcia de Orta	Almada
Portugal	Hospital Infante D. Pedro - Aveiro	Aveiro
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar Lisboa Ocidental	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos	Matosinhos
Portugal	Hospital da Luz Arrabida	Vila Nova de Gaia
Puerto Rico	Advanced Clinical Research LLC	Bayamon
Puerto Rico	Manati Ctr For Clin Research	Manati
Romania	CMI Diabet, Nutritie, Boli Metabolice "Dr Pop Lavinia"	Baia Mare	Maramures
Romania	Mariodiab Clinic SRL	Brasov
Romania	Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila	Bucharest	Bucurestii
Romania	SC Consultmed SRL	Iasi
Romania	Clinica Korall S.R.L. Satu Mare	Satu-Mare
Romania	Hospital Sf. Ioan cel Nou	Suceava
Russian Federation	Arkhangelsk Regional Clinical Hospital	Arkhangelsk
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Irkutsk State Medical Academy of Postgraduate Education	Irkutsk
Russian Federation	Limited Liability Company "AriVa-Med"	Kursk
Russian Federation	City Consultative & Diagnostic Centre #1	Saint-Petersburg
Russian Federation	Saratov regional clinical hospital	Saratov
Russian Federation	Tumen State Medical University	Tumen	Russia
Serbia	Endocrinology, Diabetes and Metabolism Diseases Clinic	Belgrade
South Africa	Netcare Alberton Hospital	Alberton
South Africa	Armansis Medical Centre	Brits	North West
South Africa	Langeberg Clinical Trials	Cape Town	Western Cape
South Africa	Dr Pillay's Rooms	Durban	KwaZulu-Natal
South Africa	Deepak Lakha	Johannesburg	Gauteng
South Africa	Hemant Makan	Johannesburg	Gauteng
South Africa	Wits Bara Clinical Trial Site	Johannesburg	Gauteng
Taiwan	Changhua Christian Hospital	Changhua City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chi Mei Medical Center	Tainan City
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Taipei Medical University Hospital	Taipei city
Turkey	Cukurova Universitesi Tip Fakultesi	Adana
Turkey	Ankara Universitesi Ibni Sina Hastanesi	Ankara	Altindag
Turkey	Gulhane Egitim Arastirma Hastanesi	Ankara
Turkey	Haseki Sultangazi	Istanbul
Turkey	T.C SB Goztepe Prof. Dr. Suleyman Yalcin City Hospital	Istanbul
Turkey	T.C. S.B. Ist Il SagMud Pendik Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Tekirdag Namik Kemal UTF	Tekirdag
United States	Javara/Privia Med Grp GA,LLC	Albany	Georgia
United States	Albuquerque Clin Trials, Inc.	Albuquerque	New Mexico
United States	Amarillo Med Spec LLP	Amarillo	Texas
United States	Texas Diabetes & Endocrinology, P.A._Austin	Austin	Texas
United States	Texas Diabetes & Endocrinology, P.A._Austin	Austin	Texas
United States	AM Diabetes And Endocrinology Center	Bartlett	Tennessee
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Holston Medical Group_Bristol	Bristol	Tennessee
United States	Northern Pines Hlth Ctr, PC	Buckley	Michigan
United States	Clinical Res Of W Florida Inc	Clearwater	Florida
United States	Central Ohio Clinical Research LLC	Columbus	Ohio
United States	John Muir Physician Network	Concord	California
United States	Univ of TX SW Med Ctr Dallas	Dallas	Texas
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Creekside Endocrine Associates, PC	Denver	Colorado
United States	Headlands Research California, LLC	Escondido	California
United States	Javara Inc.	Fayetteville	Georgia
United States	Northeast Research Institute	Fleming Island	Florida
United States	Elite Research Center	Flint	Michigan
United States	Javara Inc/Privia Md GpLLC Fst	Forest	Virginia
United States	Pri Med Grp dba/Gil Ctr Fam	Gilbert	Arizona
United States	PharmQuest Life Sciences LLC	Greensboro	North Carolina
United States	Javara Inc. / Privia Medical Group Gulf Coast PLLC	Houston	Texas
United States	PlanIt Research, PLLC	Houston	Texas
United States	PrimeCare Medical Group	Houston	Texas
United States	Protenium Clinical Research	Hurst	Texas
United States	MedStar Hlth Res Institute	Hyattsville	Maryland
United States	Jefferson City Medical Group, PC	Jefferson City	Missouri
United States	Scripps Whittier Diabetes Inst	La Jolla	California
United States	Andres Garcia-Zuniga, MD, P.A	Laredo	Texas
United States	Milton Haber, M.D.	Laredo	Texas
United States	Palm Research Center Inc.	Las Vegas	Nevada
United States	Physicians Research Assoc. LLC	Lawrenceville	Georgia
United States	The Research Group of Lexington LLC	Lexington	Kentucky
United States	Medical Investigations, Inc.	Little Rock	Arkansas
United States	Torrance Clin Res Inst, Inc.	Lomita	California
United States	DCOL Ctr for Clin Res	Longview	Texas
United States	Pacific Clinical Studies	Los Alamitos	California
United States	Downtown LA Res Ctr. Inc.	Los Angeles	California
United States	Velocity Clin Res Wstlke	Los Angeles	California
United States	International Diabetes Center	Minneapolis	Minnesota
United States	HealthStar Physicians PC	Morristown	Tennessee
United States	Southern New Hampshire Diabete	Nashua	New Hampshire
United States	New Orleans Center for Clinical Research	New Orleans	Louisiana
United States	Suncoast Clinical Research, Inc._New Port Richey	New Port Richey	Florida
United States	Mid Hudson Medical Research, PLLC	New Windsor	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Methodist Phys. Clinic	Omaha	Nebraska
United States	University of NE Med Ctr	Omaha	Nebraska
United States	Texas Diabetes & Endocinology	Round Rock	Texas
United States	Briggs Clinical Research, LLC	San Antonio	Texas
United States	Sun Research Institute	San Antonio	Texas
United States	Javara Inc Privia Grp Gulf Cst	San Marcos	Texas
United States	NorCal Endocrinology and Internal Medicine	San Ramon	California
United States	NorthShore Univ Hlth Sys	Skokie	Illinois
United States	Ileana J Tandron APMC	Slidell	Louisiana
United States	SimCare, PLLC	Sugar Land	Texas
United States	Cotton O'Neil Clin Research Ctr	Topeka	Kansas
United States	New Venture Medical Research	Wadsworth	Ohio
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Iowa Diab & Endo Res Center	West Des Moines	Iowa
United States	Metabolic Research Institute Inc	West Palm Beach	Florida
United States	Southgate Medical Group, LLP	West Seneca	New York
United States	Amherst Family Practice P.C.	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  China,  Croatia,  Finland,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  South Africa,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glycated haemoglobin (HbA1c)	% point	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) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)