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)

Diabetes Mellitus, Type 2 Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04880850
• Other study ID #: NN1436-4480
• Secondary ID: U1111-1247-52692
• Status: Completed
• Phase: Phase 3
• Start date: May 14, 2021
• Est. completion date: June 16, 2022

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 582
• Est. completion date: June 16, 2022
• Est. primary completion date: June 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin icodec
Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks
• Insulin glargine
Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 26 weeks
• Insulin aspart
Participants will receive subcutaneous (s.c.) injections of insulin aspart 2-4 times daily for 26 weeks

Locations

Country	Name	City	State
Belgium	Imeldaziekenhuis - Bonheiden - Department of Endocrinology	Bonheiden
Belgium	CHU Helora - Site Warquignies	Boussu
Belgium	Cliniques Universitaires Saint-Luc - Serv Endocrinologie - Diabétologie	Bruxelles
Belgium	UZA - UZ Antwerpen - Department of Endocrinology	Edegem
Belgium	UZ Leuven - Endocrinology	Leuven
India	Bangalore Clinisearch	Bangalore	Karnataka
India	Lifecare Hospital and Research Centre	Bangalore	Karnataka
India	Manipal Hospital, Hebbal, Bengaluru	Bengaluru	Karnataka
India	Medanta - The Medicity Multi-Speciality Hospital, Gurugram	Gurgaon	Haryana
India	Diabetes, Thyroid and Endocrine Centre	Jaipur	Rajasthan
India	Renai Medicity	Kochi	Kerala
India	BSES MG hospital	Mumbai	Maharashtra
India	Prince Aly Khan Hospital	Mumbai	Maharashtra
India	Grant Medical Foundation	Pune	Maharashtra
Italy	A. O. Universitaria S.ORSOLA-MALPIGHI - U. O. Endocrinologia	Bologna
Italy	Azienda Ospedaliero-Universitaria Renato Dulbecco	Catanzaro	Cz
Italy	Università degli Studi G. D'Annunzio	Chieti
Italy	Istituto Scientifico San Raffaele	Milano	MI
Italy	A.O.U. Università Studi della Campania "Luigi Vanvitelli"	Napoli
Italy	Policlinico Umberto I La Sapienza V Clinica Medica	Roma
Japan	Hayashi Diabetes Clinic	Chigasaki-shi	Kanagawa, Japan
Japan	Futata Tetsuhiro Clinic Meinohama	Fukuoka-shi, Fukuoka
Japan	Sasaki Hospital Internal Medicine	Hokkaido
Japan	Naka Kinen Clinic	Ibaraki
Japan	Sugimoto Clinic,Internal Medicine	Kitakyusyu-shi, Fukuoka
Japan	Shimizu Clinic Fusa	Saitama
Japan	Oyama East Clinic	Tochigi
Japan	The Jikei University Hospital Dept of Diabetes, Metabolic	Tokyo
Japan	Noritake Clinic	Ushiku-shi, Ibaraki
Mexico	Hospital Universitario Dr. José Eleuterio González_Monterrey	Monterrey	Nuevo León
Mexico	Unidad Biomedica Avanzada Monterrey	Monterrey	Nuevo León
Mexico	Centro de Investigacion Medica de Occidente S.C.	Zapopan	Jalisco
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Bethesda Diabetes Research Center en Bethesda ziekenhuis	Hoogeveen
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Romania	Mariodiab Clinic SRL	Brasov
Romania	Institutul National De Diabet Nutritie Si Boli Metabolice Prof.Dr.N.Paulescu Bucuresti- Ion Movila	Bucharest	Bucurestii
Romania	S.C. Medcon S.R.L	Buzau
Romania	Clinical Emergency Sf. Apostol Andrei Hospital	Galati
Romania	Spitalul Judetean de Urgenta Targoviste	Targoviste	Dambovita
Romania	Sc Mediab Srl	Targu Mures	Mures
Russian Federation	Arkhangelsk Regional Clinical Hospital	Arkhangelsk
Russian Federation	City Hospital #5	Barnaul
Russian Federation	KSFMU, Inrereginal Clinical Diagnostic center	Kazan
Russian Federation	Kirov Clinical Hospital #7	Kirov
Russian Federation	Limited Liability Company "AriVa-Med"	Kursk
Russian Federation	City Clinical Hospital ?52	Moscow
Russian Federation	LLC "Centr Targetnoy Terapii"	Moscow
Russian Federation	Limited Law Company "Healthy Family" Medicine Center"	Novosibirsk
Russian Federation	SPb SBHI City Outpatient clinic #37	Saint-Petersburg
Russian Federation	Regional clinical cardiology dispensary	Saratov
Russian Federation	Tumen State Medical University	Tumen	Russia
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	John Muir Physicians 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	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Valley Research	Fresno	California
United States	Physician's East Endocrinology	Greenville	North Carolina
United States	Jefferson City Medical Group, PC	Jefferson City	Missouri
United States	Holston Medical Group	Kingsport	Tennessee
United States	Physicians Research Assoc. LLC	Lawrenceville	Georgia
United States	DCOL Ctr for Clin Res	Longview	Texas
United States	Saltzer Medical Group Research	Nampa	Idaho
United States	Vanderbilt Diab Obes Clin Tri	Nashville	Tennessee
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Methodist Physicians Clin	Omaha	Nebraska
United States	Clinical Trials Research_Sacramento_0	Sacramento	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Diabetes Research Center	Tustin	California
United States	Coastal Metabolic Research Center	Ventura	California
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	MedStar Diabetes Institute	Washington	District of Columbia
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,  Belgium,  India,  Italy,  Japan,  Mexico,  Netherlands,  Romania,  Russian Federation, 

References & Publications (2)

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): — View 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. Diabe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycated haemoglobin (HbA1c)	Measured in %-point	From baseline week 0 (V2) to week 26 (V28)
Secondary	Change in fasting plasma glucose (FPG)	Measured in mmol/L	From baseline week 0 (V2) to week 26 (V28)
Secondary	Time in target-range 3.9-10.0 mmol/L (70-180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6)	Measured in % of readings	From week 22 (V24) to week 26 (V28)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 31 (V30)
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 31 (V30)
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 31 (V30)
Secondary	Time spent below 3.0 mmol/L (54 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6 )	Measured in % of readings	From week 22 (V24) to week 26 (V28)
Secondary	Time spent above 10 mmol/L (180 mg/dL) (using continuous glucose monitoring (CGM) system, Dexcom G6)	Measured in % of readings	From week 22 (V24) to week 26 (V28)
Secondary	Mean weekly insulin dose	Measured in U	From week 24 (V26) to week 26 (V28)
Secondary	Change in body weight	Measured in kg	From baseline week 0 (V2) to week 26 (V28)