The primary objective-To demonstrate that semaglutide 2.4 mg once weekly lowers the incidence risk of major adverse cardiovascular events (MACE) versus semaglutide placebo, both added to standard of care in patients with established CV disease and…
ID
Source
Brief title
Condition
- Other condition
- Cardiac disorders, signs and symptoms NEC
Synonym
Health condition
obesitas en overgewicht, vaataandoening zoals beroerte en perifeer arterieel vaatlijden
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is time from randomisation to first occurrence of a
composite endpoint consisting of: CV death, non-fatal myocardial infarction, or
non-fatal stroke.
Secondary outcome
Confirmatory secondary endpoints
Time from randomisation to:
• CV death
• All-cause death
Background summary
Glucagon-like peptide-1 (GLP-1) is a physiological regulator of appetite and
pharmacological levels of GLP-1 receptor agonists (RAs) have been shown to
induce weight loss. Semaglutide is a next generation long-acting GLP-1 RA
currently under development by Novo Nordisk.
Besides effects on appetite, GLP-1 regulates blood glucose by a
glucose-dependent stimulatory effect on insulin- and inhibitory effect on
glucagon secretion (i.e. when plasma glucose levels are above normal). GLP-1
has also several effects in the CV system. In the T2D development programme,
the CV safety of semaglutide s.c. 0.5 mg and 1.0 mg once-weekly was assessed in
a pre-approval CV outcomes trial (SUSTAIN 6; NN9535-3744) in subjects with T2D
and high CV risk. Semaglutide-treated subjects (0.5 and 1.0 mg dose groups
combined) had a significant 26%
lower risk of the primary composite outcome of death from CV causes, nonfatal
myocardialinfarction (MI), or nonfatal stroke than did those receiving placebo
(hazard ratio (HR): 0.74 [0.58; 0.95] 95%CI). The exact mechanism behind the CV
effect of semaglutide is not known. However, both pre-clinical and clinical
studies suggest that GLP-1 RAs, including semaglutide1, have direct and
beneficial effects on the CV system (including reductions in lipid levels and
blood pressure as well as anti-inflammatory effects) resulting in attenuation
of atherosclerosis. Weight loss of the magnitude seen in the recent phase 2
dose-finding trial in subjects with obesity (BMI >= 30 kg/m2) (trial
NN9536-4153) might also lower CV risk independently. Specifically, semaglutide
s.c. in doses of 0.05 to 0.4 mg once-daily was accompanied by an improvement in
CV risk factors. Semaglutide s.c. 2.4 mg once-weekly is currently also in phase
3a development for weightmanagement.
In summary, these data indicate that semaglutide s.c. has beneficial effects on
the CV system. Accordingly, semaglutide s.c. may target an unmet medical need
in subjects with established CV disease and overweight or obesity.
Study objective
The primary objective
-To demonstrate that semaglutide 2.4 mg once weekly lowers the incidence risk
of major adverse cardiovascular events (MACE) versus semaglutide placebo, both
added to standard of care in patients with established CV disease and
overweight or obesity.
Key secondary objective
To compare the effect of semaglutide 2.4 mg once weekly versus semaglutide
placebo, both added to standard of care in patients with established CV disease
and overweight or obesity with regards to:
• Mortality
Study design
This is a randomised, double-blind, parallel group, placebo-controlled trial
comparing semaglutide 2.4 mg with semaglutide placebo both administered s.c.
once weekly in patients with established CV disease and overweight or obesity.
Subjets will be randomised in a 1:1 ratio to receive either semaglutide 2.4 mg
or semaglutide placebo as an adjunct to standard-of-care.
The trial is event driven; therefore, end of trial will be scheduled according
to projected trial closure. Trial duration is expected to be up to 59 months
following randomisation.
Intervention
Once weekly semaglutide/placebo subcuteneous injection, dose 2.4 mg.
Study burden and risks
Data from the development programme for semaglutide for the T2D indication has
not revealed any safety issues that would outweigh the benefits. The recently
completed phase 2 programme with semaglutide s.c. in obesity did not reveal any
new safety issues either. The trial population will consist of subjects with
established CV disease and overweight or obesity. Assessment and treatment of
the subjects* CV risk factors, including overweight or obesity, and with
appropriate attention to the standard of care treatment will be provided
throughout the trial. It is therefore concluded that the potential benefits
from the trial will outweigh the potential risks for the semaglutide as well as
the placebo treated subjects.
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
* Male or female, age >= 45 years at the time of signing informed consent
* Body mass index (BMI) >= 27 kg/m2
* Have established CV disease as evidenced by at least one of the following:
prior myocardial infarction, prior stroke (ischemic and hemorrhagic stroke) or
symptomatic peripheral arterial disease (PAD, as evidenced by intermittent
claudication with ankle-brachial index (ABI) < 0.85 (at rest), or peripheral
arterial revascularization procedure, or amputation due to atherosclerotic
disease
Exclusion criteria
*Any of the following: myocardial infarction, stroke, hospitalisation for
unstable angina pectoris
or transient ischaemic attack within the past 60 days prior to the day of
screening
* HbA1c >= 48 mmol/mol (6.5%) as measured by the central laboratory at screening
* History of type 1 or type 2 diabetes (history of gestational diabetes is
allowed).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003380-35-NL |
| CCMO | NL65655.042.18 |