Clinical trial NCT04880850: A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4)
Official title: A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Bolus Insulin With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes on a Basal-bolus Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 582
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares insulin icodec (a new insulin taken once a week) to insulin glargine (an insulin taken once daily which is already available on the market) in people with type 2 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin glargine taken daily.

Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week or insulin glargine that participants will have to inject once a day at the same time every day. Which treatment participants will get is decided by chance. Participants will also get a mealtime insulin.The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach.

The study will last for about 8 months. participants will have 17 clinic visits and 13 phone calls with the study doctor.At 8 clinic visits participants will have blood samples taken. At 4 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. Participants will be asked to wear a sensor that measures their blood sugar all the time in 3 periods for a total of 13 weeks (about 3 months) during the study.

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.


Eligibility criteria: Inclusion Criteria:

* Male or female aged above or equal to 18 years at the time of signing informed consent.
* Diagnosed with type 2 diabetes mellitus (T2D) greater than or equal to 180 days prior to the day of screening.
* Glycated haemoglobin (HbA1c) from 7.0-10.0% (53.0 85.8 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
* Treated with once daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog (insulin aspart, faster acting insulin aspart, insulin lispro, insulin glulisine) greater than or equal to 90 days prior to the day of screening with or without any of the following anti-diabetic drugs/regimens with stable doses greater than or equal to 90 days prior to screening:

Metformin / Sulfonylureas / Meglitinides (glinides) / DPP-4 inhibitors / SGLT2 inhibitors / Thiazolidinediones / Alpha-glucosidase inhibitors / Oral combination products (for the allowed individual oral anti-diabetic drugs) / Oral or injectable GLP-1-receptor agonists

* Body mass index (BMI) below or equal to 40.0 kg/m\^2.

Exclusion Criteria:

* Any episodes (as declared by the subject or in the medical records.) of diabetic ketoacidosis within 90 days prior to the day of screening.
* Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
* Chronic heart failure classified as being in New York Heart Association Class IV at screening.
* Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to 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 (V2) to week 26 (V28)
Secondary outcomes:
measure: Change in fasting plasma glucose (FPG)
timeFrame: From baseline week 0 (V2) to week 26 (V28)
measure: Time in target-range 3.9-10.0 mmol/L (70-180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6)
timeFrame: From week 22 (V24) to week 26 (V28)
measure: Number of severe hypoglycaemic episodes (level 3)
timeFrame: From baseline week 0 (V2) to week 31 (V30)
measure: Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter)
timeFrame: From baseline week 0 (V2) to week 31 (V30)
measure: 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)
timeFrame: From baseline week 0 (V2) to week 31 (V30)
measure: Time spent below 3.0 mmol/L (54 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6 )
timeFrame: From week 22 (V24) to week 26 (V28)
measure: Time spent above 10 mmol/L (180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6)
timeFrame: From week 22 (V24) to week 26 (V28)
measure: Mean weekly insulin dose
timeFrame: From week 24 (V26) to week 26 (V28)
measure: Change in body weight
timeFrame: From baseline week 0 (V2) to week 26 (V28)
Other outcomes:
Locations:
city: Concord
country: United States
facility: John Muir Physicians Network
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research_Sacramento_0
state: California
city: Tustin
country: United States
facility: Diabetes Research Center
state: California
city: Ventura
country: United States
facility: Coastal Metabolic Research Center
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Washington
country: United States
facility: MedStar Diabetes Institute
state: District of Columbia
city: West Palm Beach
country: United States
facility: Metabolic Research Institute Inc
state: Florida
city: Lawrenceville
country: United States
facility: Physicians Research Assoc. LLC
state: Georgia
city: Nampa
country: United States
facility: Saltzer Medical Group Research
state: Idaho
city: Jefferson City
country: United States
facility: Jefferson City Medical Group, PC
state: Missouri
city: Omaha
country: United States
facility: Methodist Physicians Clin
state: Nebraska
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
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: Bartlett
country: United States
facility: AM Diabetes And Endocrinology Center
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Diab Obes Clin Tri
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Med Spec LLP
state: Texas
city: Austin
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology
state: Texas
city: Corpus Christi
country: United States
facility: Osvaldo A. Brusco MD PA
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: Dallas
country: United States
facility: UT Southwestern Med Cntr
state: Texas
city: Longview
country: United States
facility: DCOL Ctr for Clin Res
state: Texas
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis - Bonheiden - Department of Endocrinology
city: Boussu
country: Belgium
facility: CHU Helora - Site Warquignies
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc - Serv Endocrinologie - Diabétologie
city: Edegem
country: Belgium
facility: UZA - UZ Antwerpen - Department of Endocrinology
city: Leuven
country: Belgium
facility: UZ Leuven - Endocrinology
city: Gurgaon
country: India
facility: Medanta - The Medicity Multi-Speciality Hospital, Gurugram
state: Haryana
city: Bangalore
country: India
facility: Bangalore Clinisearch
state: Karnataka
city: Bangalore
country: India
facility: Lifecare Hospital and Research Centre
state: Karnataka
city: Bengaluru
country: India
facility: Manipal Hospital, Hebbal, Bengaluru
state: Karnataka
city: Kochi
country: India
facility: Renai Medicity
state: Kerala
city: Mumbai
country: India
facility: Prince Aly Khan Hospital
state: Maharashtra
city: Mumbai
country: India
facility: BSES MG hospital
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation
state: Maharashtra
city: Jaipur
country: India
facility: Diabetes, Thyroid and Endocrine Centre
state: Rajasthan
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero-Universitaria Renato Dulbecco
state: Cz
city: Milano
country: Italy
facility: Istituto Scientifico San Raffaele
state: MI
city: Bologna
country: Italy
facility: A. O. Universitaria S.ORSOLA-MALPIGHI - U. O. Endocrinologia
city: Chieti
country: Italy
facility: Università degli Studi G. D'Annunzio
city: Napoli
country: Italy
facility: A.O.U. Università Studi della Campania "Luigi Vanvitelli"
city: Roma
country: Italy
facility: Policlinico Umberto I La Sapienza V Clinica Medica
city: Chigasaki-shi
country: Japan
facility: Hayashi Diabetes Clinic
state: Kanagawa, Japan
city: Fukuoka-shi, Fukuoka
country: Japan
facility: Futata Tetsuhiro Clinic Meinohama
city: Hokkaido
country: Japan
facility: Sasaki Hospital Internal Medicine
city: Ibaraki
country: Japan
facility: Naka Kinen Clinic
city: Kitakyusyu-shi, Fukuoka
country: Japan
facility: Sugimoto Clinic,Internal Medicine
city: Saitama
country: Japan
facility: Shimizu Clinic Fusa
city: Tochigi
country: Japan
facility: Oyama East Clinic
city: Tokyo
country: Japan
facility: The Jikei University Hospital Dept of Diabetes, Metabolic
city: Ushiku-shi, Ibaraki
country: Japan
facility: Noritake Clinic
city: Zapopan
country: Mexico
facility: Centro de Investigacion Medica de Occidente S.C.
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González_Monterrey
state: Nuevo León
city: Monterrey
country: Mexico
facility: Unidad Biomedica Avanzada Monterrey
state: Nuevo León
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Hoogeveen
country: Netherlands
facility: Bethesda Diabetes Research Center en Bethesda ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Bucharest
country: Romania
facility: Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila
state: Bucurestii
city: Targoviste
country: Romania
facility: Spitalul Judetean de Urgenta Targoviste
state: Dambovita
city: Targu Mures
country: Romania
facility: Sc Mediab Srl
state: Mures
city: Brasov
country: Romania
facility: Mariodiab Clinic SRL
city: Buzau
country: Romania
facility: S.C. Medcon S.R.L
city: Galati
country: Romania
facility: Clinical Emergency Sf. Apostol Andrei Hospital
city: Tumen
country: Russian Federation
facility: Tumen State Medical University
state: Russia
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Hospital
city: Barnaul
country: Russian Federation
facility: City Hospital #5
city: Kazan
country: Russian Federation
facility: KSFMU, Inrereginal Clinical Diagnostic center
city: Kirov
country: Russian Federation
facility: Kirov Clinical Hospital #7
city: Kursk
country: Russian Federation
facility: Limited Liability Company "AriVa-Med"
city: Moscow
country: Russian Federation
facility: City Clinical Hospital №52
city: Moscow
country: Russian Federation
facility: LLC "Centr Targetnoy Terapii"
city: Novosibirsk
country: Russian Federation
facility: Limited Law Company "Healthy Family" Medicine Center"
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBHI City Outpatient clinic #37
city: Saratov
country: Russian Federation
facility: Regional clinical cardiology dispensary
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.
citation: Mathieu C, Asbjornsdottir B, Bajaj HS, Lane W, Matos ALSA, Murthy S, Stachlewska K, Rosenstock J. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023 Jun 10;401(10392):1929-1940. doi: 10.1016/S0140-6736(23)00520-2. Epub 2023 May 5.