REIMAGINE 5: A research study to see how much CagriSema (1.0 mg once weekly) lowers blood sugar and body weight compared to tirzepatide (5 mg once weekly) in people with type 2 diabetes treated with metformin, SGLT2 inhibitor or both

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

18 Oct 2024 → ongoing

Decision date (initial)

2024-08-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-509600-15-00

WHO UTN

U1111-1300-2590

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To confirm non-inferiority on change in HbA1c and/or superiority on change in body weight of CagriSema 00 mg/00 mg versus tirzepatide 5 mg in participants with T2D in inadequate glycaemic control on stable dose of metformin, SGLT2i or both

Secondary objectives 2

1. To confirm superiority of CagriSema 00 mg/00 mg versus tirzepatide 5 mg on change in HbA1c
2. To compare the effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg on: • Other parameters of glycaemic control • Achievement of ≥ 5% weight reduction • Achievement of ≥ 10% weight reduction • Achievement of ≥ 15% weight reduction • Achievement of ≥ 20% weight reduction • Blood pressure • Waist circumference • Lipids • Clinical outcome assessments

Conditions and MedDRA coding

Type 2 Diabetes

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female.
2. Age 18 years or above at the time of signing the informed consent.
3. Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening.
4. HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive) as determined by central laboratory at screening.
5. BMI ≥ 30 kg/m2 at screening. BMI will be calculated in the eCRF based on height and body weight at screening.
6. Stable daily dose(s) ≥ 90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator: - Metformin - SGLT2 inhibitor

Exclusion criteria 4

1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
2. Renal impairment with estimated Glomerular Filtration Rate < 30 ml/min/1.73 m2 as determined by central laboratory at screening.
3. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a 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.
4. Treatment with any anti-diabetic or anti-obesity medication (irrespective of indication) other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days is allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in HbA1c from baseline (week 0) to end of treatment (week 60)
2. Relative change in body weight from baseline (week 0) to end of treatment (week 60)

Secondary endpoints 17

1. Superiority of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in HbA1c from baseline (week 0) to end of treatment (week 60)
2. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in FPG from baseline (week 0) to end of treatment (week 60)
3. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of HbA1c target values of ≤6.5% (≤48 mmol/mol) at the end of treatment (week 60)
4. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of HbA1c target values of <7.0% (<53 mmol/mol) at the end of treatment (week 60)
5. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of ≥ 10% weight reduction from baseline (week 0) to end of treatment (week 60)
6. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of ≥ 5% weight reduction from baseline (week 0) to end of treatment (week 60)
7. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of ≥ 15% weight reduction from baseline (week 0) to end of treatment (week 60)
8. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Achievement of ≥ 20% weight reduction from baseline (week 0) to end of treatment (week 60)
9. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in systolic blood pressure from baseline (week 0) to end of treatment (week 60)
10. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in diastolic blood pressure from baseline (week 0) to end of treatment (week 60)
11. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in waist circumference from baseline (week 0) to end of treatment (week 60)
12. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Ratio to baseline in lipids from baseline (week 0) to end of treatment (week 60): • Total cholesterol • HDL cholesterol • LDL cholesterol • VLDL cholesterol • Triglycerides • Non-HDL cholesterol
13. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in SF-36v2 score from baseline (week 0) to end of treatment (week 60): • Physical Component Summary score • Mental Component Summary score • Vitality subscale
14. Effect of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Change in IWQOL-Lite-CT from baseline (week 0) to end of treatment (week 60): • Physical Function score • Total score
15. Safety and tolerability of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Number of TEAEs from baseline (week 0) to end of treatment (week 60)
16. Safety and tolerability of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (<54 mg/dL), confirmed by BG meter) from baseline (week 0) to end of treatment (week 60)
17. Safety and tolerability of CagriSema 00 mg/00 mg versus tirzepatide 5 mg: Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold from baseline (week 0) to end of treatment (week 60)

Investigational products

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

Test 3

Comparator 2

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 8

Locations

6 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 44 files

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

Application history

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