EX9536-4388

Novo Nordisk A/S

Novo Alle, 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

18 Jul 2023

No

Yes

29 Jun 2023

No

To demonstrate that semaglutide subcutaneously 2.4 milligram (mg) once-weekly lowers the incidence of major adverse cardiovascular events (MACE) versus semaglutide placebo, both added to standard of care in subjects with established cardiovascular (CV) disease and overweight or obesity.

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

24 Oct 2018

No

Yes

Algeria: 47

Argentina: 359

Colombia: 187

Malaysia: 187

United Kingdom: 933

United States: 3652

Austria: 120

Belgium: 128

Bulgaria: 356

Croatia: 141

Czechia: 344

Denmark: 198

Finland: 168

France: 169

Germany: 885

Greece: 354

Hungary: 135

Ireland: 71

Italy: 293

Latvia: 177

Netherlands: 342

Norway: 227

Poland: 640

Portugal: 137

Romania: 321

Spain: 186

Sweden: 183

Türkiye: 217

Ukraine: 482

Taiwan: 155

Australia: 327

Brazil: 606

Canada: 749

India: 492

Israel: 310

Japan: 357

Mexico: 341

Russian Federation: 1491

Serbia: 184

South Africa: 797

Thailand: 156

17604

5575

0

0

0

0

0

0

10876

6680

48

Overall Study (overall period)

Randomised - controlled

The trial products containing the active drug (semaglutide) and the placebo drug were visually identical and packed in a manner that maintained blinding.

Yes

Semaglutide B 3.0 milligram per milliliter (mg/mL)

Solution for injection

Subcutaneous use

Subjects received semaglutide injection once weekly at the same day of the week. Injections were to be administered by subcutaneous injection in the thigh, abdomen or upper arm at any time of day irrespective of meals.

Semaglutide placebo

Solution for injection

Subcutaneous use

Subjects received semaglutide injection once weekly at the same day of the week. Injections were to be administered by subcutaneous injection in the thigh, abdomen or upper arm at any time of day irrespective of meals.

Semaglutide

Placebo

Semaglutide

Placebo

Number of subjects with first occurrence of endpoint consisted of CV death (undetermined cause of death presumed CV death), non-fatal MI, or non-fatal stroke are presented. The endpoint was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when subject withdrew consent, date of last contact with subject for subjects who were lost to follow-up (subject did not complete the trial and did not withdraw consent), date of death. FAS included all randomised subjects. All subjects were analysed according to the treatment to which they were assigned at randomisation.

Primary

From randomisation to first occurrence of a composite endpoint

Data from the in-trial period. The endpoint was analysed using a Cox proportional hazards model with treatment as categorical fixed factor. Subjects without events of interest were censored at the end of their in-trial period.

Semaglutide v Placebo

17604

Pre-specified

0.8

2-sided

Number of subjects with first occurrence of a composite HF endpoint consisted of HF hospitalisation, urgent HF visit or CV death are presented. The endpoint was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when subject withdrew consent, date of last contact with subject for subjects who were lost to follow-up (subject did not compete the trial and did not withraw consent), date of death. FAS included all randomised. All subjects were analysed according to the treatment to which they were assigned at randomisation.

Secondary

From randomisation to first occurrence of a composite endpoint

Number of subjects with all-cause death are presented. The endpoint was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when subject withdrew consent, date of last contact with subject for subjects who were lost to follow-up (subject did not complete the trial and did not withdraw consent), date of death. FAS included all randomised subjects. All subjects were analysed according to the treatment to which they were assigned at randomisation.

Secondary

Time from randomisation to event

Number of subjects with CV death are presented. The endpoint was evalulated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when subject withdrew consent, date of last contact with subject for subjects who were lost to follow-up (subject did not complete the trial and did not withdraw consent), date of death. FAS included all randomised subjects. All subjects were analysed according to the treatment to which they were assigned at randomisation.

Secondary

Time from randomisation to event

From randomisation (week 0) up to 240 weeks

AEs are reported based on data from in-trial observation period. Not all the AEs were collected systematically and more details on the approach followed for collecting the AEs is mentioned in the section 9.2 of protocol. AEs were not separately collected for each dose level. Hence, AEs are presented in randomized arm (semaglutide vs placebo).

26

Semaglutide

Placebo