NN1535-4593

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

No

No

No

Final

08 Dec 2023

No

Yes

14 Nov 2023

No

To confirm non-inferiority of once weekly IcoSema compared with daily insulin glargine combined with insulin aspart, both treatment arms with or without oral anti-diabetic drugs (OAD), in terms of glycaemic control measured by change in Glycosylated Haemoglobin (HbA1c) from baseline after 52 weeks in subjects with type 2 diabetes (T2D) inadequately controlled with daily basal insulin using a non-inferiority margin of 0.3%-point.

The study was conducted in accordance with the Declaration of Helsinki (64th World Medical Association [WMA] general Assembly; Oct 2013) and International Council for Harmonisation (ICH) Good Clinical Practice, including archiving of essential documents, (Current Step 4 version, Nov 2016).

30 Nov 2021

No

No

Czechia: 31

France: 18

Germany: 52

Hungary: 26

India: 90

Italy: 25

Japan: 83

Malaysia: 39

Poland: 57

Slovenia: 22

South Africa: 36

Thailand: 33

Türkiye: 24

United States: 143

679

231

0

0

0

0

0

0

440

239

0

Overall Study (overall period)

Randomised - controlled

Yes

IcoSema

Solution for injection

Subcutaneous use

IcoSema was administered subcutaneously at dose strength of 700 units/mL and 2 mg/mL once weekly.

Insulin glargine and insulin aspart

Solution for injection

Subcutaneous use

Insulin glargine at dose strength 100 units/mL was administered subcutaneously once daily and 100 units/mL of insulin aspart was administered subcutaneously with meals 2-4 times daily.

IcoSema

Insulin glargine and insulin aspart

IcoSema

Insulin glargine and insulin aspart

Change from baseline (week 0) to week 52 in HbA1c is presented. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. Full Analysis Set (FAS) comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Primary

From baseline week 0 (V2) to week 52 (V54)

HbA1c and change in HbA1c from baseline to week 52 is analysed using an analysis of covariance (ANCOVA) model with region and randomised treatment as fixed factors and baseline HbA1c as covariate. Missing HbA1c values at week 52 are imputed by using multiple imputation.

IcoSema v Insulin glargine and insulin aspart

614

Pre-specified

-0.06

2-sided

Change from baseline (week 0) to week 52 in body weight is presented. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 52 (V54)

Hypoglycaemic episodes were classified as level 2 if plasma glucose levels were less than (<) 3.0 mmol/L (54 mg/dL); and level 3 had no specific glucose threshold but were associated with severe cognitive impairment requiring external assistance for recovery. End point was evaluated based on data from on-treatment period: data from date of first dose of randomised treatment as recorded on electronic case report form (eCRF) until first date of any of following: 1) last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after end of dosing interval for both treatment arms); 3) end-date for in-study data points sets. 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) were presented. Safety Analysis Set (SAS): subjects exposed to randomised treatment. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 57 (V56)

Weekly insulin dose (total) from week 50 to week 52 is presented. The end point was evaluated based on data from on-treatment period: data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. SAS included all subjects exposed to randomised treatment. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From week 50 (V52) to week 52 (V54)

Time in range was defined as 100 times the number of recorded measurements in glycemic range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. Percentage of time in range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 were presented. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From week 48 (V50) to week 52 (V54)

Time spent below threshold was defined as 100 times the number of recorded measurements below the threshold, divided by the total number of recorded measurements. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. Percentage of time spent less than 3.0 mmol/L (54 mg/dL) using CGM system, Dexcom G6 were presented. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From week 48 (V50) to week 52 (V54)

DTSQs was used to assess a subject's treatment satisfaction. This questionnaire contained 8 components and measures the treatment for diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment. The value presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 52 (V54)

Time spent above threshold is defined as 100 times the number of recorded measurements above the threshold, divided by the total number of recorded measurements. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. Percentage of time spent more than 10.0 mmol/L (180 mg/dL) using continuous CGM system, Dexcom G6 were presented. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From week 48 (V50) to week 52 (V54)

Change in FPG from baseline (week 0) to week 52 is presented. The end point was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct subject-site contact; 2) withdrawal for subjects who withdraw their informed consent; 3) the last subject-investigator contact as defined by the investigator for subjects who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for subjects who die before any of the above. FAS comprised all randomised subjects. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 52 (V54)

Hypoglycaemic episodes were classified as level 2 if plasma glucose levels were < 3.0 mmol/L (54 mg/dL). The end point was evaluated based on data from on-treatment period: data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) were presented. SAS included all subjects exposed to randomised treatment. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 57 (V56)

Hypoglycaemic episodes were classified as level 3 if there was no specific glucose threshold but were associated with severe cognitive impairment requiring external assistance for recovery. The end point was evaluated based on data from on-treatment period: data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. Number of severe hypoglycaemic episodes (level 3) were presented. SAS included all subjects exposed to randomised treatment. Overall number of subjects analyzed = subjects with available data for this end point.

Secondary

From baseline week 0 (V2) to week 57 (V56)

From baseline (week 0) to week 57

All the presented adverse events (AEs) are treatment emergent adverse events (TEAEs). TEAE: events that had onset date during on-treatment period, time period in which subjects was considered exposed to trial product. SAS included all subjects exposed to randomised treatment.

26.1

Insulin Glargine & Insulin Aspart

IcoSema