The primary objective is 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…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is time to first occurrence of a composite endpoint
consisting of: Onset of persistent >= 50% reduction in estimated glomerular
filtration rate (eGFR) (CKD-EPI) compared with baseline, onset of persistent
eGFR (CKD-EPI) < 15 mL/min/1.73 m2, initiation of chronic renal replacement
therapy (dialysis or kidney transplantation), renal death, or cardiovascular
death.
Secondary outcome
The key secondary endpoints are annual rate of change in eGFR (CKD-EPI) (total
eGFR slope), time to first occurrence of a composite major adverse
cardiovascular event (MACE) endpoint (consisting of: non-fatal myocardial
infarction, non-fatal stroke, CV death) and all-cause death.
Background summary
Chronic kidney disease (CKD) and diabetes often co-exist and for the majority
of cases, the kidney damage and/or reduced kidney function is caused directly
by longstanding and poorly controlled diabetes. Improved glycaemic control has
been suggested to reduce the progression of CKD in type 2 diabetes (T2D) and
both glycaemic and blood pressure control are key recommendations in
international treatment guidelines for CKD in T2D. Yet there remains a major
unmet medical need to improve the treatment of CKD in patients with T2D. The
purpose of this trial is to demonstrate that semaglutide subcutaneously (s.c.)
delays the progression of renal impairment and lowers the risk of renal and
cardiovascular (CV) mortality in subjects with T2D and CKD.
Study objective
The primary objective is 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.
The key secondary objectives are to compare the effect of treatment with
semaglutide versus placebo, both added to standard-of-care in subjects with
type 2 diabetes and chronic kidney disease with regards to cardiovascular
morbidity, peripheral artery disease, glycaemic control, body weight, blood
pressure and safety.
Study design
This is a multi-centre, international, randomised, double-blind,
parallel-group, placebo-controlled trial comparing semaglutide 1.0 mg versus
placebo both administered s.c. once weekly and added to standard-of-care in
subjects with T2D and pre-existing CKD. Subjects will be randomised 1:1 to
receive either semaglutide or placebo. Randomisation will be stratified by use
of sodium glucose cotransporter-2 (SGLT-2) inhibitors (yes versus no) at
baseline. The number of subjects with inclusion eGFR >= 60 mL/min/1.73 m2 will
be capped at 20%.
Intervention
Once weekly semaglutide/placebo as subcutaneous injection, 1.0 mg.
Study burden and risks
Data from the development programme for semaglutide has not revealed any safety
issues that would outweigh the benefits of participation in this trial. The
trial population will consist of T2D subjects with CKD. Assessment of diabetes
and CKD and appropriate attention to the standard-of-care treatment will be
provided throughout the trial. It is therefore concluded that the potential
benefits from trial participation will outweigh the potential risks for the
semaglutide as well as the placebo treated subjects.
Flemingweg 8
Alphen a/d Rijn 2408 AV
NL
Flemingweg 8
Alphen a/d Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
- Male or female, age 18 years or older at the time of signing informed
consent. Japan: 20 years;
- Diagnosed with type 2 diabetes mellitus;
- HbA1c (glycated haemoglobin) equal to or below 10% (equal to or below 86
mmol/mol);
- Renal impairment defined either by;
a) serum creatinine-based eGFR (estimated glomerular filtration rate) equal to
or above 50 and equal to or below 75 mL/min/1.73 m^2 (chronic kidney disease -
epidemiology collaboration, CKD-EPI) and UACR (urinary albumin-to-creatinine
ratio) above 300 and below 5000 mg/g
or
b) serum creatinine-based eGFR equal to or above 25 and below 50 mL/min/1.73
m^2 (CKD-EPI) and UACR above 100 and below 5000 mg/g;
- Treatment with maximum labelled or tolerated dose of a
renin-angiotensin-aldosterone;
system (RAAS) blocking agent including an angiotensin converting enzyme (ACE)
inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is
contraindicated or not tolerated. Treatment dose must be stable for at least 4
weeks prior to the date of the laboratory assessments used for determination of
the inclusion criteria for renal impairment and kept stable until screening.
Exclusion criteria
- Congenital or hereditary kidney diseases including polycystic kidney disease,
autoimmune kidney diseases including glomerulonephritis or congenital urinary
tract malformations;
- Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days
prior to screening;
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris
or transient ischaemic attack within 60 days prior to the day of screening;
- Presently classified as being in New York Heart Association (NYHA) Class IV
heart failure;
- Planned coronary, carotid or peripheral artery revascularisation;
- Current (or within 90 days) chronic or intermittent haemodialysis or
peritoneal dialysis;
- 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
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 | EUCTR2018-002878-50-NL |
| ClinicalTrials.gov | NCT03819153 |
| CCMO | NL68794.056.19 |