REDEFINE 3: A research study to see the effects of CagriSema in people living with diseases in the heart and blood vessels

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

28 Feb 2023 → ongoing

Decision date (initial)

2024-08-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-506924-94-00

EudraCT number

2021-005855-35

WHO UTN

U1111-1270-0943

ClinicalTrials.gov

NCT05669755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To confirm non-inferiority of CagriSema 2.4mg/2.4mg versus placebo with respect to time to first major adverse cardiovascular event (MACE)

Secondary objectives 1

1. To confirm superiority of CagriSema 2.4mg/2.4mg versus placebo with respect to time to first MACE

Conditions and MedDRA coding

Cardiovascular disease

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, European Medicines Agency, Medicines Evaluation Board, Swedish Medical Products Agency, Danish Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female
2. Age above or equal to 55 years at the time of signing informed consent
3. Body mass index (BMI) ≥ 25.0 kg/m2
4. 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, MR angiography, 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)
5. For participants with T2D at screening, the following inclusion criteria also apply: Diagnosed with type 2 diabetes mellitus (T2D) ≥ 180 days before screening. HbA1c 6.5%-10% (48-86 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 (OADs) (metformin, α-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

Exclusion criteria 6

1. Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 60 days before screening
2. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
3. Heart failure classified as being in New York Heart Association (NYHA) Class IV at screening
4. Treatment with any GLP-1 RA or a medication with GLP-1 activity within 90 days before screening
5. End stage renal disease defined as eGFR < 15 mL/min/1.73 m2, as measured by the central laboratory at screening
6. Chronic or intermittent haemodialysis or peritoneal dialysis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first occurrence of MACE, a composite endpoint consisting of: • CV death • non-fatal myocardial infarction • non-fatal stroke

Secondary endpoints 32

1. CCI
2. CCI
3. Time to first occurrence of a composite endpoint consisting of: • Onset of persistent ≥40% reduction in eGFRcr (CKD EPI) compared with baseline • Onset of persistent eGFRcr (CKD-EPI) <15 mL/min/1.73 m2 • Initiation of chronic kidney replacement therapy (dialysis or kidney transplantation) • Kidney death • CV death
4. CCI
5. Time to first occurrence of an expanded MACE composite endpoint consisting of: • CV death • non-fatal myocardial infarction • non-fatal stroke • coronary revascularisation • unstable angina requiring hospitalisation
6. Time to first occurrence of a composite endpoint consisting of: • all-cause death • non-fatal myocardial infarction • non-fatal stroke
7. Time to first occurrence of myocardial infarction (fatal and non fatal)
8. Time to first occurrence of stroke (fatal and non fatal)
9. Relative change in body weight
10. Change in waist circumference
11. Change in systolic blood pressure (SBP)
12. Change in diastolic blood pressure (DBP)
13. ratio to baseline in lipids: • Total cholesterol • HDL cholesterol • LDL cholesterol • VLDL cholesterol • Triglycerides • Free fatty acids
14. Change in HbA1c
15. Change in SF-36v2: • Physical Component Summary score • Mental Component Summary score
16. Number of TESAEs
17. Number of event adjudication committee (EAC)-confirmed malignant neoplasms
18. Number of severe hypoglycaemic episodes (level 3) (only for participants with T2D at screening)
19. Ratio to baseline in hsCRP
20. Ratio to baseline in TNF-α
21. Ratio to baseline in IL-6
22. Ratio to baseline in IL-1β
23. Change in pain intensity rated by Numerical Rating Scale (NRS)
24. Change in Pittsburgh Sleep Quality Index (PSQI)
25. Change in neuropathy status by baseline neuropathy group (painful neuropathy, painless neuropathy or no neuropathy)
26. CCI
27. CCI
28. CCI
29. Time to first occurrence of a composite endpoint consisting of: • Onset of persistent macro albuminuria • Onset of persistent ≥40% reduction in eGFRcr (CKD EPI) compared with baseline • Onset of persistent eGFRcr (CKD-EPI) <15 mL/min/1.73 m2 • Initiation of chronic kidney replacement therapy (dialysis or kidney transplantation) • Kidney death
30. Change in eGFRcr (CKD-EPI)
31. Ratio to baseline in UACR
32. Change in waist-to-height ratio

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 16

Locations

9 EU/EEA countries · 168 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 96 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications