The cardiovascular safety of cagrilintide 2.4 mg s.c. in combination with semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) once-weekly in participants with obesity and established cardiovascular disease

JRCT ID: jRCT2031220672

Registered date:02/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Obesity and cardiovascular disease
• Date of first enrollment: 01/03/2023
• Target sample size: 75
• Countries of recruitment: Canada,Japan,Austria,Japan,India,Japan,South Africa,Japan,Italy,Japan,Serbia,Japan,Argentina,Japan,Denmark,Japan,Germany,Japan,Mexico,Japan,Netherlands,Japan,United Kingdom,Japan,Brazil,Japan,Colombia,Japan,Turkey,Japan,Bulgaria,Japan,France,Japan,Spain,Japan,United States,Japan,Poland,Japan,Ireland,Japan
• Study type: Interventional
• Intervention(s): This is an interventional 156-week, randomised, double-blind, placebo-controlled, two-armed, parallel-group, multicentre, multinational clinical study primarily intended to assess the CV safety of CagriSema 2.4 mg/2.4 mg versus placebo, both administered subcutaneously (s.c.) once-weekly and added to standard of care in participants with obesity and established CVD. The study design will also allow for evaluation of neoplasm safety, due to the 3-year treatment duration.

Outcome(s)

Primary Outcome

To confirm non-inferiority of CagriSema 2.4 mg/2.4 mg versus placebo with respect to time to first major adverse cardiovascular event (MACE) when at least 122 MACE have been accrueda*.
*An interim DBL is planned for when at least 122 first MACE are accrued. If 122 MACE have been accrued earlier than the planned DBL of the two global phase 3a studies (NN9838-4608 and NN9838-4609), the interim DBL will be postponed until the DBL for studies NN9838-4608 and NN9838-4609. Thus, the interim DBL will contain more than 122 first MACE in case the accrual of events occurs faster than anticipated

Key inclusion & exclusion criteria

• Age minimum: >= 55age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Male or female
-Age above or equal to 55 years at the time of signing informed consent.
-Body mass index (BMI) greater than or equal to (>=) 30.0 kilograms per meter square
-Established CVD as evidenced by at least one of the following:
-Prior myocardial infarction
-Prior stroke (ischemic or haemorrhagic stroke)
-Symptomatic peripheral arterial disease (PAD) defined as at least one of the following:
a.Intermittent claudication with an Ankle-brachial index (ABI) < 0.85 at rest
b.Intermittent claudication with a >= 50% stenosis in a lower extremity peripheral artery documented by X-ray angiography, magnetic resonance (MR) angiography, computed tomography (CT) angiography or Doppler ultrasound
c.Prior revascularization procedure of a lower extremity peripheral artery
d.Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis)
For participants with T2D at screening the following inclusion criteria also apply:
-Diagnosed with type 2 diabetes mellitus (T2D) more than 180 days before screening
-HbA1c 7%-10% (53-86 mmol/mol) (both inclusive), as measured by central laboratory at screening.
-Treatment with either:
a.Lifestyle intervention alone
b.1-3 marketed oral antidiabetic drugs (OAD)s (metformin, alpfa-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), DPP4-inhibitors, thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local label
c.Basal insulin alone or in combination with up to two marketed OADs (refer to b. above), all according to local label

Exclude criteria

-Clinically significant or severe hypoglycaemia within 6 months before screening or history of hypoglycaemia unawareness
- Renal impairment with estimated glomerular filtration rate (eGFR)< 30 mL/min/1.73 m2, as measured by the central laboratory at screening
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before 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

Related Information

• Primary Sponsor: Ryoma Akihito Hirose
• Secondary ID(s): NCT05669755