REIMAGINE 3: A research study to see how much CagriSema lowers blood sugar and body weight compared to placebo in people with type 2 diabetes treated with once-daily basal insulin with or without metformin

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

12 Apr 2024 → 20 Oct 2025

Decision date (initial)

2024-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2022-502679-43-00

WHO UTN

U1111-1283-0754

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To confirm superiority of CagriSema (00 mg/00 mg and 00 mg/00 mg) versus placebo on change in HbA1c in participants with T2D in inadequate glycaemic control on once-daily basal insulin +/- metformin

Secondary objectives 3

1. To confirm superiority of CagriSema (00 mg/00 mg and 00 mg/00 mg) versus placebo on: Change in body weight, Achievement of ≥ 10% weight reduction, Achievement of ≥ 15% weight reduction, Other parameters of glycaemic control, Change in insulin dose
2. To compare the effect of CagriSema (00 mg/00 mg and 00 mg/00 mg) versus placebo on: Other parameters of glycaemic control, Achievement of ≥ 5% weight reduction, Achievement of ≥ 20% weight reduction, Waist circumference, Blood pressure, Inflammation, Lipids, Clinical outcome assessments, Leptin and soluble leptin receptor
3. To compare the safety and tolerability of CagriSema (00 mg/00 mg and 00 mg/00 mg) versus placebo

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 (sex at birth).
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. On stable once-daily dose of basal insulin (minimum of 0.25 IU/kg/day and/or 20 IU/day) alone or in combination with metformin (at effective or maximum tolerated dose as judged by the investigator) for 90 days prior to screening.
5. HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive) as determined by central laboratory at screening.
6. BMI ≥ 25 kg/m2 at screening. BMI will be calculated in the eCRF based on height and body weight at screening.

Exclusion criteria 6

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. For South Africa: please see country-specific requirements in Appendix 13 (Section 10.13).
3. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
4. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. 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.
5. Known hypoglycaemic unawareness as indicated by the Investigator according to Clarke’s questionnaire question 8.
6. Recurrent severe hypoglycaemic episodes within the last year as judged by the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in HbA1c from baseline (week 0) to end of treatment (week 40)

Secondary endpoints 24

1. Relative change in body weight from baseline (week 0) to end of treatment (week 40)
2. Achievement of ≥ 10 % weight reduction from baseline (week 0) to end of treatment (week 40)
3. Achievement of ≥ 15 % weight reduction from baseline (week 0) to end of treatment (week 40)
4. Achievement of HbA1c target values of <7.0% (<53 mmol/mol) at end of treatment (week 40)
5. Achievement of HbA1c target values of ≤6.5% (≤48 mmol/mol) at end of treatment (week 40)
6. Change in Fasting Plasma Glucose (FPG) from baseline (week 0) to end of treatment (week 40)
7. Change in insulin dose from baseline (week 0) to end of treatment (week 40)
8. Achievement of insulin dose = 0 U at end of treatment (week 40)
9. Change in mean 7-point SMPG profiles from baseline (week 0) to end of treatment (week 40): Mean 7-point profile, Mean postprandial increment (over all meals)
10. Achievement of ≥ 5% weight reduction from baseline (week 0) to end of treatment (week 40)
11. Achievement of ≥ 20 % weight reduction from baseline (week 0) to end of treatment (week 40)
12. Change in waist circumference from baseline (week 0) to end of treatment (week 40)
13. Change in systolic blood pressure (SBP) from baseline (week 0) to end of treatment (week 40)
14. Change in diastolic blood pressure (DBP) from baseline (week 0) to end of treatment (week 40)
15. Ratio to baseline in high sensitivity C-reactive protein (hsCRP) from baseline (week 0) to end of treatment (week 40)
16. Ratio to baseline in lipids from baseline (week 0) to end of treatment (week 40): Non-HDL cholesterol, Triglycerides, Low-density lipoprotein, Very low-density lipoprotein (VLDL) cholesterol, High-density lipoprotein (HDL) cholesterol, Total cholesterol, Free fatty acids
17. Change in experienced level of energy, as measured by the SF-36v2 Vitality score from baseline (week 0) to end of treatment (week 40)
18. Change in SF-36v2 score from baseline (week 0) to end of treatment (week 40): Physical Component Summary score, Mental Component Summary score
19. Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score from baseline (week 0) to end of treatment (week 40)
20. Ratio to baseline in leptin from baseline (week 0) to end of treatment (week 40)
21. Ratio to baseline in soluble leptin receptor from baseline (week 0) to end of treatment (week 40)
22. Number of Treatment Emergent Adverse Events (TEAEs) from baseline (week 0) to end of treatment + 7 weeks
23. 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 + 7 weeks
24. 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 + 7 weeks

Investigational products

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

Test 5

Placebo 1

Auxiliary 5

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 12

Locations

1 EU/EEA country · 5 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 15 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