A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 1)

• ClinicalTrials.gov Identifier: NCT04460885
• Recruitment Status: Completed
• First Posted: July 8, 2020
• Last Update Posted: July 6, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: July 6, 2020
• First Posted Date: July 8, 2020
• Last Update Posted Date: July 6, 2023
• Actual Study Start Date: November 25, 2020
• Actual Primary Completion Date: May 29, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2020)

Change in HbA1c [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]

%-point

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 6, 2020)

• Time in target range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V42) to week 52 (V46) ]
  % of readings
• Change in fasting plasma glucose (FPG) [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]
  mmol/L
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter) [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]
  Number of episodes
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 83 (V63) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter) [ Time Frame: From baseline week 0 (V2) to week 83 (V63) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 83 (V63) ]
  Number of episodes
• Mean weekly insulin dose [ Time Frame: From week 50 (V44) to week 52 (V46) ]
  U
• Change in body weight [ Time Frame: From baseline week 0 (V2) to week 52 (V46) ]
  kg
• Time spent < 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V42) to week 52 (V46) ]
  % of readings
• Time spent > 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 48 (V42) to week 52 (V46) ]
  % of readings

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before
• Official Title: A 78-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Treatment, in Insulin naïve Subjects With Type 2 Diabetes

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 get is decided by chance.

The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach. The study will last for about 1 ½ years. Participants will have 37 clinic visits and 26 phone calls with the study doctor. At 11 clinic visits participant will have blood samples taken. At 8 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 the blood sugar all the time in 5 periods of about one month during the study (about 5 months in total). Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Insulin icodec
  Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 78 weeks.
• Drug: Insulin glargine
  Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 78 weeks

Study Arms

• Experimental: Insulin icodec
  Insulin icodec + non-insulin anti-diabetic drugs. The pre-trial non-insulin anti-diabetic background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period
  Intervention: Drug: Insulin icodec
• Active Comparator: Insulin glargine
  Insulin glargine + non-insulin anti-diabetic drugs. The pre-trial non-insulin anti-diabetic background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period
  Intervention: Drug: Insulin glargine

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2021): 984
• Original Estimated Enrollment (submitted: July 6, 2020): 970
• Actual Study Completion Date: December 1, 2022
• Actual Primary Completion Date: May 29, 2022 (Final data collection date for primary outcome measure)

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) 180 days or more prior to the day of screening.
• HbA1c from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
• Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
• Stable daily dose(s) 90 days or more prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s): a. Any metformin formulations at least or greater than 1500 mg or maximum tolerated or effective dose. b. Any metformin combination formulations equal to or above 1500 mg or maximum tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes including combinations ((equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose): Sulfonylureas, Meglitinides (glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral anti-diabetic drugs), Oral or injectable glucagon-like peptide 1 (GLP-1) receptor agonists
• Body mass index (BMI) equal to or below 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Croatia, India, Israel, Italy, Japan, Mexico, Poland, Puerto Rico, Russian Federation, Slovakia, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04460885
• Other Study ID Numbers: NN1436-4477; U1111-1247-3878 ( Other Identifier: World Health Organization (WHO) ); 2020-000442-34 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Transparency (1452); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: July 2023