A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3) (ONWARDS 3)

• ClinicalTrials.gov Identifier: NCT04795531
• Recruitment Status: Completed
• First Posted: March 12, 2021
• Last Update Posted: November 7, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: March 10, 2021
• First Posted Date: March 12, 2021
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: March 24, 2021
• Actual Primary Completion Date: June 23, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2021)

Change in HbA1c (glycated haemoglobin) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]

%-point

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 10, 2021)

• Change in fasting plasma glucose (FPG) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  mmol/L
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 31 (V30) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) [ Time Frame: From baseline week 0 (V2) to week 31 (V30) ]
  Number of episodes
• 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) [ Time Frame: From baseline week 0 (V2) to week 31 (V30) ]
  Number of episodes
• Number of severe hypoglycaemic episodes (level 3) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  Number of episodes
• Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  Number of episodes
• 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) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  Number of episodes
• Change in body weight [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  Kg
• Mean weekly insulin dose [ Time Frame: From week 24 (P26) to week 26 (V28) ]
  U

• 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 Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3)
• Official Title: A 26-week Double Blinded, Multiregional, Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Drugs, in Insulin naïve Subjects With Type 2 Diabetes.

Brief Summary

This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (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 degludec taken daily.

Participants will get their study medicine in an injection pen. Participants will get a pen for weekly injection and one for daily injection. One will be icodec or degludec and the other will be dummy medicine. The treatment participants get is decided by chance. Participants and the study staff will not know which active medicine they get.

The insulin is injected with a needle in a skin fold in the thigh. The study could last for about 8 months. Participants will have 13 clinic visits and 17 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.

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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Insulin icodec

  You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

  Subcutaneously (under the skin) injections

• Drug: Placebo insulin icodec

  You will get a pen for weekly injection and one for daily injection. One will be insulin degludec 100 units/mL and the other will be placebo.

  Subcutaneously (under the skin) injections

• Drug: Insulin degludec

  You will get a pen for weekly injection and one for daily injection. One will be degludec 100 units/mL and the other will be placebo.

  Subcutaneously (under the skin) injections

• Drug: Placebo insulin degludec

  You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo.

  Subcutaneously (under the skin) injections

Study Arms

• Experimental: Once weekly insulin icodec + once daily placebo
  Participants will get once daily and once weekly injections
  Interventions:

  • Drug: Insulin icodec
  • Drug: Placebo insulin degludec
• Experimental: Once weekly placebo and once daily insulin degludec
  Participants will get once daily and once weekly injections
  Interventions:

  • Drug: Placebo insulin icodec
  • Drug: Insulin degludec

• 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 3, 2022): 588
• Original Estimated Enrollment (submitted: March 10, 2021): 774
• Actual Study Completion Date: June 23, 2022
• Actual Primary Completion Date: June 23, 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 T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
• HbA1c (glycated haemoglobin) 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) greater than or equal to 90 days prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s):

  a.) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b.) Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c.) Any of the following oral anti-diabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose).:Sulfonylureas - Meglitinides (glinides) - DPP-4 inhibitors - SGLT2 inhibitors - Thiazolidinediones - Alpha-glucosidase inhibitors - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - 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 (NYHA) 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: Argentina, Austria, Brazil, Canada, China, Czechia, Denmark, France, Mexico, Puerto Rico, Taiwan, United States

Administrative Information

• NCT Number: NCT04795531
• Other Study ID Numbers: NN1436-4479; U1111-1247-5218 ( Other Identifier: World Health Organization (WHO) ); 2020-000472-37 ( 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 (dept. 1452); Novo Nordisk A/S

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