Clinical trial NCT06269107: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-02-21
Enrollment: 474
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 (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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change in glycated haemoglobin (HbA1c)
timeFrame: From baseline (week 0) to week 40
Secondary outcomes:
measure: Change in body weight
timeFrame: From baseline (week 0) to week 40
measure: Time in range 3.9-10.0 millimoles per liter (mmol/L) (70-180 milligram per deciliter [mg/dL])
timeFrame: From week 36 to week 40
measure: Time spent less than (<) 3.0 mmol/L (54 mg/dL)
timeFrame: From week 36 to week 40
measure: Time spent greater than (>) 10.0 mmol/L (180 mg/dL)
timeFrame: From week 36 to week 40
measure: Weekly basal insulin dose
timeFrame: From week 38 to week 40
measure: Change in fasting plasma glucose (FPG)
timeFrame: From baseline (week 0) to week 40
measure: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction
timeFrame: From baseline (week 0) to week 40
measure: 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)
timeFrame: From baseline (week 0) to week 45
measure: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)
timeFrame: From baseline (week 0) to week 45
measure: Number of severe hypoglycaemic episodes (level 3)
timeFrame: From baseline (week 0) to week 45
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Inst
state: California
city: Lancaster
country: United States
facility: First Valley Med Grp Lancaster
state: California
city: Palm Springs
country: United States
facility: Desert Oasis Hlthcr Med Group
state: California
city: Palm Springs
country: United States
facility: Desert Oasis Hlthcr Med Group
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research_Sacramento
state: California
city: Fleming Island
country: United States
facility: Northeast Research Institute
state: Florida
city: Winter Haven
country: United States
facility: Clinical Research of Cent FL
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials
state: Idaho
city: Chicago
country: United States
facility: Cedar-Crosse Research Center
state: Illinois
city: Skokie
country: United States
facility: Endeavor Health
state: Illinois
city: Topeka
country: United States
facility: Cotton-O'Neil Diab & Endo Ctr
state: Kansas
city: Omaha
country: United States
facility: Methodist Phys. Clinic
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Clin Trials, Inc.
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College - Endo
state: New York
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Greenville
country: United States
facility: Physician's East Endocrinology
state: North Carolina
city: Canton
country: United States
facility: Diab & Endo Assoc of Stark Co
state: Ohio
city: Maumee
country: United States
facility: Advanced Medical Research
state: Ohio
city: Wadsworth
country: United States
facility: New Venture Medical Research
state: Ohio
city: Amarillo
country: United States
facility: Amarillo Med Spec LLP
state: Texas
city: Austin
country: United States
facility: Velocity Clinical Research- Cedar Park
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Res-Dallas
state: Texas
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Ctr of FW
state: Texas
city: Lampasas
country: United States
facility: Fmc Science, Llc
state: Texas
city: San Antonio
country: United States
facility: Quality Research Inc
state: Texas
city: San Antonio
country: United States
facility: Flourish Research
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Newport News
country: United States
facility: TPMG Clinical Research
state: Virginia
city: Beijing
country: China
facility: Peking University People's Hospital-Endocrinology
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University-Endocrinology
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Huizhou
country: China
facility: Huizhou Central People's Hospital-Endocrinology
state: Guangdong
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Zhenjiang
country: China
facility: The Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pudong New Area People's Hospital-Endocrinology
state: Shanghai
city: Athens
country: Greece
facility: Evangelismos Hospital
city: Athens
country: Greece
facility: 'G. Gennimatas' General Hospital of Athens
city: Athens
country: Greece
facility: "Laiko" General Hospital of Athens
city: Kalamata
country: Greece
facility: General Hospital of Kalamata
city: Larissa
country: Greece
facility: Univ Gen Hospital Larisa
city: Thessaloniki
country: Greece
facility: "Thermi" Private Hosital
city: Bangalore
country: India
facility: Ramaiah Memorial Hospital
state: Karnataka
city: Mysore
country: India
facility: Mysore Medical College and Research Institute
state: Karnataka
city: Mumbai
country: India
facility: BYL Nair Hospital and T N Medical College Department of endo
state: Maharashtra
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharashtra
city: Mumbai
country: India
facility: BSES MG hospital
state: Maharashtra
city: Pune
country: India
facility: Chellaram Diabetes Institute
state: Maharashtra
city: Jaipur
country: India
facility: SMS Medical College & Hospital
state: Rajasthan
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: Lucknow
country: India
facility: Udyaan Health Care
state: Uttar Pradesh
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education & Research
city: L'Aquila
country: Italy
facility: Ospedale San Salvatore, Dipartimento Medico ASL1 Abruzzo, UOC Diabetologia
state: Abbruzzo
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza reparto endocrinologia
state: FG
city: Ancona
country: Italy
facility: I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani
city: Ceccano (Frosinone)
country: Italy
facility: Casa della Salute di Ceccano (FR)
city: Chiavari (genova)
country: Italy
facility: ASL 4 Chiavarese
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia
city: Rome
country: Italy
facility: A.O.U. Policlinico Umberto I
city: Miyazaki-shi
country: Japan
facility: Heiwadai Hospital
state: Miyazaki
city: Chiba
country: Japan
facility: Tokuyama clinic
city: Hokkaido
country: Japan
facility: Oodouri Diabetes, Internal medicine Clinic
city: Tochigi
country: Japan
facility: Oyama East Clinic
city: Tokyo
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo
country: Japan
facility: Fukuwa Clinic
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
state: Podlaskie
city: Bialystok
country: Poland
facility: SNZOZ Lege Artis
city: Krakow
country: Poland
facility: Grazyna Pulka Specjalistyczny Osrodek "All-Med"
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: Lublin
country: Poland
facility: Velocity Nova Sp. z o.o.
city: Warszawa
country: Poland
facility: NBR Polska Tomasz Klodawski
city: Warszawa
country: Poland
facility: PANSTWOWY INSTYTUT MEDYCZNY MSWiA
city: Zabrze
country: Poland
facility: Clinhouse Centrum Medyczne
city: Staszow
country: Poland
facility: Velocity Nova Sp. z o.o.
state: Świętokrzyskie
city: Bayamon
country: Puerto Rico
facility: Advanced Clinical Research LLC
city: Johannesburg
country: South Africa
facility: Dr R Dulabh
state: Gauteng
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
state: Gauteng
city: Roodepoort
country: South Africa
facility: Roodepoort Medicross Clinical Research Centre
state: Gauteng
city: KwaDukuza
country: South Africa
facility: Clinical Research Institute of South Africa
state: KwaZulu Natal
city: Durban
country: South Africa
facility: Dr Pillay's Rooms
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Langeberg Clinical Trials
state: Western Cape
city: Antalya
country: Turkey
facility: Akdeniz University Tip Fakultesi Hastanesi
city: Istanbul
country: Turkey
facility: Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi
city: Tekirdag
country: Turkey
facility: Tekirdag Namık Kemal UTF
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: