A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin (ONWARDS 2)

• ClinicalTrials.gov Identifier: NCT04770532
• Recruitment Status: Completed
• First Posted: February 25, 2021
• Last Update Posted: May 15, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: February 22, 2021
• First Posted Date: February 25, 2021
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: March 5, 2021
• Actual Primary Completion Date: January 27, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 22, 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: February 22, 2021)

• Change in fasting plasma glucose (FPG) [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  mmol/L
• 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 22 (V24) to week 26 (V28) ]
  % of readings
• Change in DTSQs (Diabetes Treatment Satisfaction Questionnaire) in total treatment satisfaction [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  Score 0-36 6 items scored on a scale of 0 to 6. The higher the score the greater the satisfaction with treatment
• 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
• Time spent below 3.0 mmol/L (54 mg/dL) Using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 22 (V24) to week 26 (V28) ]
  % of readings
• Time spent above 10 mmol/L (180 mg/dL) Using continuous glucose monitoring (CGM) system, Dexcom G6 [ Time Frame: From week 22 (V24) to week 26 (V28) ]
  % of readings
• Mean weekly insulin dose [ Time Frame: From week 24 (V26) to week 26 (V28) ]
  U
• Change in body weight [ Time Frame: From baseline week 0 (V2) to week 26 (V28) ]
  kg

• 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 Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin
• Official Title: A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec, Both With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes Treated With Basal Insulin

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 either get insulin icodec that participants will have to inject once a week on the same day of the week or insulin degludec 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 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.

• 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 degludec
  Participants will receive subcutaneous (s.c.) injections of insulin degludec once daily for 26 weeks
• Drug: Insulin Icodec
  Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks

Study Arms

• Experimental: Insulin icodec
  Insulin icodec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The 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 degludec
  Insulin degludec + non-insulin anti-diabetic drugs. Pre-trial non-insulin anti-diabetic background medication throughout the entire trial except from sulfonylureas and glinides, which must be discontinued at randomisation. The background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period.
  Intervention: 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.
• Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, Watada H, Kellerer M. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023 Jun;11(6):414-425. doi: 10.1016/S2213-8587(23)00093-1. Epub 2023 May 3. Erratum In: Lancet Diabetes Endocrinol. 2023 Jul;11(7):e9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2021): 526
• Original Estimated Enrollment (submitted: February 22, 2021): 520
• Actual Study Completion Date: March 1, 2022
• Actual Primary Completion Date: January 27, 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 greater than or equal to 180 days prior to the day of screening.
• 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 or twice daily basal insulin (Neutral Protamine Hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL): 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Germany, Japan, Korea, Republic of, Poland, Portugal, South Africa, Ukraine, United States

Administrative Information

• NCT Number: NCT04770532
• Other Study ID Numbers: NN1436-4478; U1111-1247-4945 ( Other Identifier: World Health Organization (WHO) ); 2020-000454-10 ( 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: May 2023