2026-525209-11-00WithdrawnPhase 3
Efficacy and safety of zenagamtide s.c. once weekly compared to insulin glargine s.c. once daily in participants with type 2 diabetes and increased cardiovascular risk inadequately controlled on 1–3 oral glucose-lowering medications (AMBITION 7)
Novo Nordisk A/S83 sites in 4 countries110 target enrollmentStarted: September 11, 2026Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Withdrawn
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 110
- Locations
- 83
- Primary Endpoint
- "Change in haemoglobin A1c (HbA1c) from baseline (week 0) to week 52 'Time to first occurrence of a 4-point MACE endpoint consisting of: -CV death -non-fatal myocardial infarction -non-fatal stroke -hospitalisation for unstable angina from baseline (week 0) to CCI (up to 104 weeks or more)"
Study Overview
Brief Summary
To confirm non-inferiority of zenagamtide versus insulin glargine on change in glycated haemoglobin (HbA1c) and on time to first composite 4-point MACE in participants with type 2 diabetes (T2D) and increased cardiovascular (CV) risk, not in adequate glycaemic control on 1–3 marketed oral glucose-lowering medications.
Eligibility Criteria
- Ages
- 18 years to 64 years (18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
- •Male or female (sex assigned at birth, inclusive of all gender identities).
- •Age 45 years or above at the time of signing the informed consent.
- •Diagnosed with type 2 diabetes (T2D) ≥ 180 days before screening.
- •Treatment with 1–3 marketed oral glucose-lowering medications (metformin, glinide, thiazolidinedione, sodium-glucose cotransporter-2 inhibitors (SGLT2i), α-glucosidase inhibitors (AGI), or sulfonylureas (SU) as a single agent or in combination) according to local label. Treatment with oral glucose-lowering medications must be stable (same drug(s), stable daily dose(s)) for CCI before screening.
- •Have haemoglobin A1c (HbA1c) as determined by central laboratory at screening: - CCI if background glucose-lowering medications does not include a SU, or - CCI if background glucose-lowering medications includes a SU
- •Increased risk of cardiovascular events as evidenced by at least one of the following (a-e): a. Prior myocardial infarction (MI) b. Documented coronary artery disease defined by at least one of the following: i. ≥ 50% stenosis of coronary artery on angiography or other imaging modality ii. Ischaemia documented by stress test with any imaging modality iii. Prior unstable angina with electrocardiogram (ECG) changes iv. Prior coronary artery bypass graft or prior percutaneous coronary intervention c. Prior stroke (ischemic or haemorrhagic stroke) d. History of chronic kidney disease based on medical records or as judged by the investigator and CCI, as determined by central laboratory at screening e. Symptomatic peripheral arterial disease (PAD) defined as at least one of the following: i. Intermittent claudication with an ankle-brachial index (ABI) < 0.85 at rest ii. Intermittent claudication with a ≥ 50% stenosis in a lower extremity peripheral artery documented by X-ray angiography, magnetic resonance (MR) angiography, computer tomography (CT) angiography or Doppler ultrasound iii. Prior revascularisation procedure of a lower extremity peripheral artery iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis)
Exclusion Criteria
- •Myocardial infarction, stroke, transient ischaemic attack or hospitalisation for unstable angina pectoris within 60 days before screening.
- •Known hypoglycaemic unawareness as indicated by the investigator according to Clarke’s questionnaire question.
- •Uncontrolled thyroid disease as per investigator’s discretion
- •Any episodes of diabetic ketoacidosis CCI before screening.
- •Planned coronary, carotid or peripheral artery revascularisation.
- •Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening.
- •CCI, as determined by central laboratory at screening.
- •Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria CCI before screening. However, insulin treatment for gestational diabetes is allowed as well as short term insulin treatment for a maximum of 14 consecutive days.
- •Treatment with glucagon-like-peptide-1 (GLP-1) receptor agonists (RA), dual GLP1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment), dipeptidyl peptidase 4 (DPP-4) inhibitors or amylin analogues CCI before screening.
- •Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) 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 non-dilated examination.
Arms & Interventions
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10143 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10146 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: zenagamtide B 10176 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10142 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10145 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10141 (Drug)
NNC0487-0111 B 10143, NNC0487-0111 B 10146, zenagamtide B 10176, NNC0487-0111 B 10145, NNC0487-0111 B 10141, NNC0487-0111 B 10144, NNC0487-0111 B 10142
Test
Intervention: NNC0487-0111 B 10144 (Drug)
Lantus SoloStar 100 units/ml solution for injection in a pre-filled pen
Comparator
Intervention: Lantus SoloStar 100 units/ml solution for injection in a pre-filled pen (Drug)
Outcomes
Primary Outcomes
"Change in haemoglobin A1c (HbA1c) from baseline (week 0) to week 52 'Time to first occurrence of a 4-point MACE endpoint consisting of: -CV death -non-fatal myocardial infarction -non-fatal stroke -hospitalisation for unstable angina from baseline (week 0) to CCI (up to 104 weeks or more)"
"Change in haemoglobin A1c (HbA1c) from baseline (week 0) to week 52 'Time to first occurrence of a 4-point MACE endpoint consisting of: -CV death -non-fatal myocardial infarction -non-fatal stroke -hospitalisation for unstable angina from baseline (week 0) to CCI (up to 104 weeks or more)"
Secondary Outcomes
- CCI
- - Relative change in body weight - Change in HbA1c from baseline (week 0) to week 52
- Time to first occurrence of a 3-point MACE endpoint consisting of: -CV death -non-fatal myocardial infarction -non-fatal stroke from baseline (week 0) to CCI (up to 104 weeks or more)
- - Change in waist circumference - Change in systolic blood pressure - Change in high-sensitivity C-reactive protein (hsCRP) - Change in Triglycerides and Non-high-density lipoprotein (non-HDL) cholesterol from baseline (week 0) to week 52
Investigators
EU Submission Hub
Scientific
Novo Nordisk A/S
Study Sites (83)
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