Clinical trial NCT05013229: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-08-19
Enrollment: 679
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in HbA1c
timeFrame: From baseline week 0 (V2) to week 52 (V54)
Secondary outcomes:
measure: Change in body weight
timeFrame: From baseline week 0 (V2) to week 52 (V54)
measure: 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)
timeFrame: From week 0 (V52) to week 52 (V54)
measure: Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
timeFrame: From week 48 (V50) to week 52 (V54)
measure: Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
timeFrame: From week 48 (V50) to week 52 (V54)
measure: Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
timeFrame: From week 48 (V50) to week 52 (V54)
measure: Change in fasting plasma glucose (FPG)
timeFrame: From baseline week 0 (V2) to week 52 (V54)
measure: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction
timeFrame: From baseline week 0 (V2) to week 52 (V54)
measure: Number of severe hypoglycaemic episodes (level 3)
timeFrame: From baseline week 0 (V2) to week 57 (V56)
measure: Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter)
timeFrame: From baseline week 0 (V2) to week 57 (V56)
measure: Weekly insulin dose (total)
timeFrame: From week 50 (V52) to week 52 (V54)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Wht Diab Inst La Jolla
state: California
city: Los Angeles
country: United States
facility: Downtown LA Res Ctr. Inc.
state: California
city: San Diego
country: United States
facility: San Diego Family Care
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates
state: Colorado
city: Fleming Island
country: United States
facility: Northeast Research Institute
state: Florida
city: Jacksonville
country: United States
facility: Northeast Res Inst. Inc.
state: Florida
city: Miramar
country: United States
facility: South Broward Research LLC
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County, Inc.
state: Florida
city: Orlando
country: United States
facility: Florida Inst For Clin Res
state: Florida
city: Roswell
country: United States
facility: Endo Res Solutions Inc
state: Georgia
city: Nampa
country: United States
facility: Saltzer Medical Group Research
state: Idaho
city: Skokie
country: United States
facility: Endeavor Health
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diab & Endo Res Center
state: Iowa
city: Lexington
country: United States
facility: The Research Group of Lexington LLC
state: Kentucky
city: Hyattsville
country: United States
facility: MedStar Hlth Res Institute
state: Maryland
city: Buckley
country: United States
facility: Northern Pines Hlth Ctr, PC
state: Michigan
city: Las Vegas
country: United States
facility: Palm Research Center Inc-Vegas
state: Nevada
city: Nashua
country: United States
facility: Southern NH Diabetes and Endocrinology
state: New Hampshire
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Statesville
country: United States
facility: Piedmont Healthcare/Research
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Canton
country: United States
facility: Diab & Endo Assoc of Stark Co
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Wadsworth
country: United States
facility: New Venture Medical Research
state: Ohio
city: Simpsonville
country: United States
facility: Hillcrest Clinical Research
state: South Carolina
city: Bartlett
country: United States
facility: AM Diabetes And Endocrinology Center
state: Tennessee
city: Chattanooga
country: United States
facility: Univ Diab & Endo Consultants
state: Tennessee
city: Morristown
country: United States
facility: HealthStar Physicians PC
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Med Spec LLP
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Res-Dallas
state: Texas
city: Houston
country: United States
facility: PlanIt Research, PLLC
state: Texas
city: Hurst
country: United States
facility: Protenium Clinical Research
state: Texas
city: Laredo
country: United States
facility: Andres Garcia-Zuniga, MD, P.A
state: Texas
city: Plano
country: United States
facility: Clinical Investigations Of Texas
state: Texas
city: San Antonio
country: United States
facility: Briggs Clinical Research, LLC
state: Texas
city: San Antonio
country: United States
facility: NE Clin Res of San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Simcare Medical Research, LLC
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Renton
country: United States
facility: Rainier Clin Res Ctr Inc
state: Washington
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
state: Czech Republic
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
state: Czech Republic
city: Brno
country: Czechia
facility: University Hospital U sv. Anny
city: Brno
country: Czechia
facility: University Hospital U sv. Anny
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
city: Praha 1
country: Czechia
facility: Diabet2 s.r.o.
city: Praha 1
country: Czechia
facility: Diabetologická a interní ambulance Diabet2
city: Praha 6
country: Czechia
facility: Fledip s.r.o.
city: Praha 8
country: Czechia
facility: ResTrial s.r.o.
city: Praha
country: Czechia
facility: III. interni klinika VFN a 1. LK UK v Praze
city: Praha
country: Czechia
facility: Institut klinicke a experimentalni mediciny_Praha
city: Praha
country: Czechia
facility: Fledip s.r.o.
city: LA ROCHE-sur-YON cedex 9
country: France
facility: Centre Hospitalier Departemental Vendee- La Roche Sur Yon
city: Le Creusot
country: France
facility: Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2
city: Paris
country: France
facility: Aphp-Hopital Lariboisiere-1
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2
city: Venissieux
country: France
facility: Centre de Recherche Clinique Portes Du Sud
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
city: Hamburg
country: Germany
facility: Wendisch/Dahl Hamburg
city: Münster
country: Germany
facility: Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
city: Oldenburg in Holstein
country: Germany
facility: RED-Institut für medizinische Forschung und Fortbildung GmbH
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Zentrum für klinische Studien Alexander Segner
city: Budapest
country: Hungary
facility: Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.
city: Budapest
country: Hungary
facility: Szőcs Depot Egészségügyi Szolgáltató Kft.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem II. Belgyógyászati Klinika
city: Budapest
country: Hungary
facility: ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.
city: Békéscsaba
country: Hungary
facility: Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház
city: Ahmedabad
country: India
facility: Apollo Hospital, Ahmedabad
state: Gujarat
city: Gandhinagar
country: India
facility: Apollo Hospital International Ltd
state: Gujarat
city: Bangalore
country: India
facility: Diacon Hospital Private Limited
state: Karnataka
city: Indore
country: India
facility: TOTALL Diabetes Hormone Institute
state: Madhya Pradesh
city: Pune
country: India
facility: Sahyadri Speciality Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Pune
country: India
facility: chelleram Diabetes Institute
state: Maharashtra
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education & Research
state: Punjab
city: Ludhiana
country: India
facility: Christian Medical College and Hospital
state: Punjab
city: Mohali
country: India
facility: Fortis Heart Institute and Multispeciality Hospital
state: Punjab
city: Jaipur
country: India
facility: Diabetes, Thyroid and Endocrine Centre
state: Rajasthan
city: Chennai
country: India
facility: Madras Diabetes Research Foundation
state: Tamil Nadu
city: Vellore
country: India
facility: Christian Medical College Hospital, Vellore
state: Tamil Nadu
city: Lucknow
country: India
facility: Medanta Lucknow Hospital
state: Uttar Pradesh
city: Ahmedabad
country: India
facility: Swasthya Diabetes Care
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero-Universitaria Renato Dulbecco
state: CZ
city: Roma
country: Italy
facility: Pol. Uni. Campus Biomedico UOC Endocrinologia e Diabetologia
state: RM
city: Milano
country: Italy
facility: Azienda Ospedaliera Luigi Sacco
city: Partinico
country: Italy
facility: Ospedale Civico Partinico di Palermo
city: Sesto San Giovanni (MI)
country: Italy
facility: IRCCS Multimedica
city: Miyazaki-shi
country: Japan
facility: Heiwadai Hospital
state: Miyazaki
city: Kawagoe-shi
country: Japan
facility: Asano Clinic
state: Saitama, Japan
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical Univ. Hospital_Diabetes, Metabolism and Endocrinology
state: Tokyo
city: Aichi
country: Japan
facility: TOSAKI Clinic for Diabetes and Endocrinology_Diabetes and Endocrinology
city: Chiba-shi, Chiba
country: Japan
facility: Akaicho Clinic
city: Chuo-ku, Tokyo
country: Japan
facility: The Institute of Medical Science, Asahi Life Foundation
city: Ibaraki
country: Japan
facility: Naka Kinen Clinic
city: Mito-shi, Ibaraki
country: Japan
facility: Minami Akatsuka Clinic
city: Osaka
country: Japan
facility: Takatsuki Red Cross Hospital
city: Tokyo
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo
country: Japan
facility: Fukuwa Clinic
city: Kota Bharu
country: Malaysia
facility: Hospital Universiti Sains Malaysia_Kota Bharu, Kelantan
state: Kelantan
city: Cheras
country: Malaysia
facility: Hospital Universiti Kebangsaan Malaysia
state: Kuala Lumpur
city: Seri Manjung
country: Malaysia
facility: Hospital Seri Manjung
state: Perak
city: Sungai Buloh
country: Malaysia
facility: University Technology MARA (UiTM) - Puncak Alam
state: Selangor
city: Sungai Buloh
country: Malaysia
facility: University Technology MARA (UiTM) - Sg Buloh
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Wilayah Persekutuan Kuala Lumpur
city: Alor Setar
country: Malaysia
facility: Klinik Kesihatan Simpang Kuala
city: Miri, Sarawak
country: Malaysia
facility: Miri Hospital
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
state: Podlaskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
state: Pomorskie
city: Bialystok
country: Poland
facility: SNZOZ Lege Artis
city: Lodz
country: Poland
facility: Gabinet Lekarski Malgorzata Saryusz-Wolska
city: Lodz
country: Poland
facility: Centrum Terapii Współczesnej J.M. Jasnorzewska S.K.A.
city: Warszawa
country: Poland
facility: NBR Polska Tomasz Klodawski
city: Kocevje
country: Slovenia
facility: Healthcare centre Kocevje
city: Koper
country: Slovenia
facility: Healthcare Centre Koper
city: Ljubljana
country: Slovenia
facility: UKC Ljubljana, Endocrinology and Diabetes
city: Murska Sobota
country: Slovenia
facility: General Hospital Murska Sobota
city: Nova Gorica
country: Slovenia
facility: General Hospital Nova Gorica_Diabetes
city: Bloemfontein
country: South Africa
facility: Medi-Clinic Bloemfontein
state: Free State
city: Lenasia
country: South Africa
facility: Lenasia Clinical Trial Centre
state: Gauteng
city: Pretoria
country: South Africa
facility: Prof P. Joshi
state: Gauteng
city: Cape Town
country: South Africa
facility: Spoke Research Inc
state: Western Cape
city: Bangkoknoi, Bangkok
country: Thailand
facility: Siriraj Hospital_Bangkoknoi, Bangkok
state: Bangkok
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
state: Mueang Chiang Mai District
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Nakhon Ratchasima
country: Thailand
facility: Maharat Nakhon Ratchasima Hospital
city: Adana
country: Turkey
facility: Baskent Universitesi Adana
city: Ankara
country: Turkey
facility: Gulhane Egitim Arastirma Hastanesi
city: Antalya
country: Turkey
facility: Akdeniz University Tip Fakultesi Hastanesi
city: Aydin
country: Turkey
facility: Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi
city: Denizli
country: Turkey
facility: Pamukkale Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: TC SB Ist.İl Sag.Müd.Prof.Dr.Cemil Tascioglu Sehir Hastanesi
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References: