A Research Study Investigating How Well Zenagamtide Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease Treated With Once Daily Basal Insulin Alone or in Combination With Metformin, SGLT2i, or Both (AMBITION 2)

Novo Nordisk

Status and phase: Not yet enrolling; Phase 3

Conditions: Chronic Kidney Disease; Type 2 Diabetes

Treatments: Other: Placebo; Drug: Zenagamtide

Study type: Interventional

Funder types: Industry

Identifiers

NCT07931547

U1111-1335-3313 (Other Identifier)

2026-525471-13 (Other Identifier)

NN9489-8034

Details and patient eligibility

About

The study is testing zenagamtide in participants with type 2 diabetes and chronic kidney disease. The purpose of this clinical study is to find out if zenagamtide is safe and effective for treating people who have type 2 diabetes. Participants will either get zenagamtide or placebo. Which treatment participants get is decided by chance. Zenagamtide is a new medicine that doctors cannot prescribe yet, but it has been tested in humans before.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female (sex assigned at birth).
• Age 18 years or above at the time of signing the informed consent.
• Diagnosed with type 2 diabetes (T2D) above or equal to 180 days before screening.
• On stable once-daily dose of basal insulin (minimum of 0.25 Unit per kilogram per day or 20 Unit per day) at the investigator's discretion alone or in combination with metformin, sodium-glucose cotransporter 2 inhibitors (SGLT2i) or both (at stable effective or maximum tolerated dose as judged by the investigator) prior to screening. Basal insulin dose is considered stable when all doses during this period are within the range defined by plus minus 20%.
• History of chronic kidney disease based on medical records or as judged by the investigator.
• Treatment with maximum labelled or tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated, in the opinion of the investigator. Treatment dose must be stable for at least 30 days prior to screening.

Exclusion criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method.
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria before screening. However, insulin treatment for gestational diabetes or short-term insulin treatment for a maximum of 14 consecutive days is allowed.
• Treatment with glucagon-like-peptide-1 (GLP-1) receptor agonists (RA), dual GLP-1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment) or amylin analogues before screening.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-vascular endothelial growth factor within 180 days before screening or are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye 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 nondilated examination.
• Myocardial infarction, stroke, transient ischaemic attack or hospitalisation for unstable angina pectoris within 60 days before screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at screening.
• Planned coronary, carotid or peripheral artery revascularisation.
• Lupus nephritis or antineutrophil cytoplasmic (ANCA)-associated vasculitis.
• Any primary or secondary kidney disease requiring immunosuppressive therapy prior to screening.
• Chronic or intermittent haemodialysis or peritoneal dialysis before screening.
• Combination use of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) within 30 days prior to screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will receive placebo matched to zenagamtide subcutaneously.

Treatment:

Other: Placebo

Zenagamtide

Experimental group

Description:

Participants will receive zenagamtide subcutaneously.

Treatment:

Drug: Zenagamtide