NN9535-4321

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

06 Feb 2024

No

Yes

09 Jan 2024

Yes

Primary objective: To demonstrate that semaglutide delays the progression of renal impairment and lowers the risk of renal and cardiovascular mortality compared to placebo, both added to standard-of-care, in subjects with type 2 diabetes and chronic kidney disease

This trial was conducted in accordance with the principles of the Declaration of Helsinki, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, including the archiving of essential documents, and United States Food and Drug Administration (FDA) 21 Code of Federal Regulation (CFR) 312.50 and 312.56.

17 Jun 2019

No

Yes

Canada: 159

United States: 706

Belgium: 51

Bulgaria: 75

France: 79

Germany: 73

Greece: 101

Hungary: 130

Italy: 94

Netherlands: 48

Poland: 78

Slovakia: 100

Spain: 72

United Kingdom: 62

Australia: 59

China: 30

India: 231

Israel: 61

Japan: 256

Malaysia: 82

Thailand: 109

Türkiye: 84

Argentina: 128

Brazil: 124

Mexico: 82

Russian Federation: 270

South Africa: 101

Ukraine: 88

3533

901

0

0

0

0

0

0

1285

2218

30

Overall (overall period)

Randomised - controlled

Yes

Semaglutide

Solution for injection

Subcutaneous use

Semaglutide was administered once weekly subcutaneously.

Placebo

Solution for injection

Subcutaneous use

Semaglutide matched placebo was administered once weekly subcutaneously.

Semaglutide

Placebo

Semaglutide

Placebo

Number of subjects from time of randomisation to first occurrence of an onset of persistent greater than or equal to (≥) 50 percent (%) reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration [CKD-EPI]) compared to baseline; onset of persistent eGFR (CKD-EPI) <15 millilitre per minute per 1.73 metre square (mL/min/1.73 m^2); initiation of chronic renal replacement therapy (dialysis or kidney transplantation); renal death; and cardiovascular (CV) death combined that were reported in this endpoint. FAS included all unique randomised subjects who were grouped according to the treatment assigned at randomisation.

Primary

From randomisation (week 0) to end-of-trial (up to 61 months or more)

Time from randomisation to first composite renal event was analysed using a Cox proportional hazards model with treatment as categorical fixed factor and stratified by use of sodium glucose cotransporter-2 (SGLT-2) inhibitor (yes/no) at baseline. Based on the available number of events for analysis, the nominal signifi-cance level was updated to 0.01612 using the Lan-DeMets alpha spending function. eGFR was calculated using the CKD-EPI formula.

Semaglutide v Placebo

3533

Pre-specified

0.76

2-sided

Number of subjects who reported first occurrence of non-fatal acute myocardial infarction, non-fatal stroke, and CV death combined data were presented from Week 0 up to Week 234 during on-treatment period. MACE consisted of non-fatal acute myocardial infarction, cardiovascular death and non-fatal stroke. First on-treatment period is defined as period from date of first dose until first time where no dose had been administered within 5 weeks (35 days) or end of the in-trial period, whichever came first. FAS included all unique randomised subjects who were grouped according to the treatment assigned at randomisation.

Secondary

From randomisation (week 0) to end-of-trial (up to 61 months or more)

Number of subjects who reported occurence of deaths from Week 0 up to Week 234 during in-trial period were presented. All cause death consisted of renal death, cardiovascular death, non-cardiovascular and non-renal death, and undetermined cause of death. In-trial observation period was defined as the period from date of randomisation to the first of (both inclusive): date of follow-up visit, date when subject withdrew consent, date of last contact with subject (for subject lost to follow-up), and date of death. FAS included all unique randomised subjects who were grouped according to the treatment assigned at randomisation.

Secondary

From randomisation (week 0) to end-of-trial (up to 61 months or more)

Annual rate of change in Total eGFR slope CKD-EPI were reported from baseline at Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was de-fined as the period from date of randomisation to the first of (both inclusive): date of follow-up visit, date when subject withdrew consent, date of last contact with subject (for subject lost to follow-up), and date of death. FAS included all unique randomised subjects who were grouped according to the treatment assigned at randomisation.

Secondary

From randomisation (week 0) to end-of-trial (up to 61 months or more)

From Week 0 up to Week 238

The safety evaluation was based on the FAS using the in-trial observation period which was defined as the period from date of randomisation to the first of (both inclusive): date of follow-up visit, date when subject withdrew consent, date of last contact with subject (for subject lost to follow-up), and date of death.

26

Placebo

Semaglutide