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 Semaglutide (COMBINE 2)

Diabetes Mellitus, Type 2 Clinical Trial

— COMBINE 2  

Official title:

A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Semaglutide, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With a GLP 1 Receptor Agonist. COMBINE 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05259033
• Other study ID #: NN1535-4592
• Secondary ID: U1111 1260 82682
• Status: Completed
• Phase: Phase 3
• Start date: April 11, 2022
• Est. completion date: January 16, 2024

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 semaglutide 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 semaglutide. Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries. Participants will get IcoSema or semaglutide, which they 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 18 clinic visits, 34 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 683
• Est. completion date: January 16, 2024
• Est. primary completion date: December 13, 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% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
• Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
• Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. 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 (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above.
• Body mass index (BMI) below or equal to 40.0 kg/m^2.

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 (as declared by the participant or in the medical records) of diabetic ketoacidosis 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.
• 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
IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.
• Semaglutide 1 mg
Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.

Locations

Country	Name	City	State
Brazil	Instituto de Ciências Farmacêuticas de Estudos e Pesquisas	Aparecida de Goiania	Goias
Brazil	Centro de Diabetes Curitiba	Curitiba	Parana
Brazil	Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV	Curitiba	Parana
Brazil	Centro de Diabetes Metabolismo e Endocrinologia	Fortaleza	Ceara
Brazil	Instituto São José dos Campos em Pesquisas Médicas	São José dos Campos	Sao Paulo
Brazil	BR Trials - Ensaios Clínicos e Consultoria Ltda.	São Paulo	Sao Paulo
Canada	LMC (Thornhill)	Concord	Ontario
Canada	Wharton Med Clin Trials	Hamilton	Ontario
Canada	Western Univ. Cnt for Studies in Fam Med	London	Ontario
Canada	LMC Clin Rsrch Inc. (Montreal)	Montreal	Quebec
Canada	Recherche GCP Research	Montreal	Quebec
Canada	Medical Trust Clinics, Inc.	Oshawa	Ontario
Canada	Recherche Clinique Sigma inc	Quebec
Canada	LMC Clin Rsrch Inc. (Montreal)	Saint-Laurent	Quebec
Canada	Bluewater Clin Res Group,Inc	Sarnia	Ontario
Canada	LMC Endo Centres Ltd.(Bayview)	Toronto	Ontario
China	Peking University People's Hospital	Beijing	Beijing
China	Changzhou No.2 People's Hospital, Yanghu Branch	Changzhou	Jiangsu
China	Chongqing University Three Gorges Hospital	ChongQing	Chongqing
China	Anhui Provincial Hospital	Hefei	Anhui
China	Huizhou Central People's Hospital	Huizhou	Guangdong
China	Jinan Central Hospital	Jin'an	Shandong
China	The Second Affiliated Hospital of Nanjing Medical University_Nanjing	Nanjing	Jiangsu
China	Shanghai Fifth People's Hospital	Shanghai	Shanghai
China	Shanghai Huashan Hospital, Affiliated to Fudan University	Shanghai	Shanghai
China	General Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Zhu Xianyi Memorial Hospital of Tianjin Medical University	Tianjin	Tianjin
France	Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume	Bois-Guillaume
France	Les Hopitaux de Chartres-Hopital Louis Pasteur	Le Coudray
France	Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1	Le Creusot
France	Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1	Saint Herblain
France	Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2	Toulouse
France	Groupe Hospitalier Mutualiste Des Portes Du Sud	Venissieux
Greece	'G. Gennimatas' General Hospital of Athens	Athens
Greece	Evangelismos Hospital	Athens
Greece	Iatriko Psychicou Private Clinic	Athens
Greece	Univ Gen Hospital Larisa, Endocrinology & Metabolic Disease	Larissa
Greece	"Ippokrateio" G.H. of Thessaloniki	Thessaloniki
Greece	"Thermi" Private Hosital	Thessaloniki
Greece	General Hospital of Thessaloniki "G.Papanikolaou"	Thessaloniki
Greece	General Hospital of Thessaloniki 'G. Gennimatas	Thessaloniki
Hungary	MED-TIMA Kft.	Budapest
Hungary	Debreceni Egyetem Belgyógyászati Klinika	Debrecen	Hajdu-Bihar
Hungary	Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület	Debrecen	Hajdu-Bihar
Hungary	PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum	Pécs	Baranya Vármegye
Israel	Linn clinic - Clalit Health Services	Haifa
Israel	Clalit sick fund Herzlia	Herzlia
Israel	Diabetes Clinic Wolfson MC	Holon
Israel	Diabetes Unit Hadassah Ein Karem MC	Jerusalem
Israel	Diabetes Clinic Meir MC	Kfar Saba
Israel	Endrocrinolgy Clinic - Sheba Medical Center	Tel Hashomer
Japan	The Institute of Medical Science, Asahi Life Foundation	Chuo-ku, Tokyo
Japan	Futata Tetsuhiro Clinic Meinohama	Fukuoka-shi, Fukuoka
Japan	Gifu University Hospital	Gifu
Japan	Naka Kinen Clinic	Ibaraki
Japan	Heiwadai Hospital	Miyazaki-shi	Miyazaki
Japan	Takatsuki Red Cross Hospital	Osaka
Japan	Shimizu Clinic Fusa	Saitama
Japan	Soka Sugiura Internal Medicine Clinic_Internal Medicine	Saitama
Japan	Shinden Higashi Clinic	Sendai-shi, Miyagi
Russian Federation	Irkutsk State Medical Academy of Postgraduate Education	Irkutsk
Russian Federation	National Medical Research Center of Endocrinology	Moscow
Russian Federation	Limited Law Company "Healthy Family" Medicine Center"	Novosibirsk
Russian Federation	BHI of Omsk Region "City Hospital ? 3"	Omsk
Russian Federation	Penza Regional Clinical Hospital named after N.N. Burdenko	Penza
Russian Federation	Rostov State Medical University_Rostov-on-Don	Rostov-on-Don
Russian Federation	Polyclinic #2 in Yoshkar-Ola	Yoshkar-Ola
Slovakia	Diabetologicka ambulancia DIADAN, s.r.o. Kosice	Kosice
Slovakia	DIOLI s.r.o.	Kosice
Slovakia	FNsP L. Pasteura	Kosice
Slovakia	HUMAN-CARE s.r.o.	Kosice
Slovakia	DIA - KONTROL s.r.o.	Levice
Slovakia	MUDr. Alena Lomencikova, s.r.o	Turcianske Teplice
Sweden	Primary Care Trial Center, PTC ,Gothia Forum	Göteborg
Sweden	Enheten för Kliniska Studier (EKS), Örebro	Örebro
Sweden	Centrum for Diabetes, Academical Specialist Centrum	Stockholm
Switzerland	Luzerner Kantonsspital	Luzern 16
Switzerland	Kantonsspital Olten	Olten
Switzerland	Diabetes Adipositas Zentrum Zürich	Zollikerberg
Taiwan	Chung Shan Medical University Hospital	Taichung City
Taiwan	Chi Mei Medical Center	Tainan City
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou Branch	Taoyuan city
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 Diab & Endo, P.A.	Austin	Texas
United States	Texas Diabetes & Endocrinology	Austin	Texas
United States	AM Diabetes And Endocrinology Center	Bartlett	Tennessee
United States	Univ of AL at Birmingham_BRM	Birmingham	Alabama
United States	Northern Pines Hlth Ctr, PC	Buckley	Michigan
United States	Diab & Endo Assoc of Stark Co	Canton	Ohio
United States	Chattanooga Medical Research, LLC	Chattanooga	Tennessee
United States	John Muir Physician Network	Concord	California
United States	Osvaldo A. Brusco MD PA	Corpus Christi	Texas
United States	North Texas Endocrine Center	Dallas	Texas
United States	UT Southwestern Med Cntr	Dallas	Texas
United States	Northeast Research Institute	Fleming Island	Florida
United States	Javara Inc. / Privia Medical Group LLC_Forest	Forest	Virginia
United States	Javara Inc/Privia Md GpLLC Fst	Forest	Virginia
United States	Diabetes and Thyroid Ctr of FW	Fort Worth	Texas
United States	Pri Med Grp dba/Gil Ctr Fam	Gilbert	Arizona
United States	PharmQuest Life Sciences LLC	Greensboro	North Carolina
United States	East West Med Res Inst	Honolulu	Hawaii
United States	MedStar Hlth Res Institute	Hyattsville	Maryland
United States	Est Cst Inst for Rsrch,Jksnvil	Jacksonville	Florida
United States	Northeast Res Inst. Inc.	Jacksonville	Florida
United States	Palm Research Center Inc-Vegas	Las Vegas	Nevada
United States	John J Shelmet, MD	Lawrenceville	New Jersey
United States	DCOL Ctr for Clin Res	Longview	Texas
United States	Velocity Clin Res Wstlke	Los Angeles	California
United States	South Broward Research LLC	Miramar	Florida
United States	Adult Medicine of Lake County, Inc.	Mount Dora	Florida
United States	Saltzer Medical Group Research	Nampa	Idaho
United States	TPMG Clinical Research	Newport News	Virginia
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Florida Inst For Clin Res	Orlando	Florida
United States	Florida Institute For Clinical Research	Orlando	Florida
United States	Oviedo Medical Research, LLC	Oviedo	Florida
United States	Thomas Jefferson Univ Di Rsrch Ctr	Philadelphia	Pennsylvania
United States	Texas Diabetes & Endocrinology_Round Rock	Round Rock	Texas
United States	Chrysalis Clinical Research	Saint George	Utah
United States	NE Clin Res of San Antonio	San Antonio	Texas
United States	NorthShore Univ Hlth Sys	Skokie	Illinois
United States	Ileana J Tandron APMC	Slidell	Louisiana
United States	Sugar Lakes Family Practice PA	Sugar Land	Texas
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Clinical Research Institute of Arizona	Sun City West	Arizona
United States	Premier Medical Center, Inc.	Toluca Lake	California
United States	New Venture Medical Research	Wadsworth	Ohio
United States	Metabolic Research Institute Inc	West Palm Beach	Florida
United States	Southgate Medical Group, LLP	West Seneca	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  China,  France,  Greece,  Hungary,  Israel,  Japan,  Russian Federation,  Slovakia,  Sweden,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glycated haemoglobin (HbA1c)	Percentage-point	From baseline week 0 (V2) to week 52 (V54)
Secondary	Change in fasting plasma glucose (FPG)	Measured in mmol/L	From baseline week 0 (V2) to week 52 (V54)
Secondary	Change in body weight	Measured in 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)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)