Effects of empagliflozin on plasma glucose in patients with HNF1A-MODY: a randomized, double-blind, crossover trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Steno Diabetes Center Copenhagen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

11 Oct 2023 → 29 Nov 2024

Decision date (initial)

2023-06-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate the glucose-lowering effect of empagliflozin 25 mg once-daily in patients with HNF1A-MODY.

Conditions and MedDRA coding

Maturity-onset diabetes of the young type 3 (HNF1A-MODY)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed consent
2. Diabetes caused by a heterozygous mutation (pathogenic or likely pathogenic according to ACMG criteria) in the HNF1A-gene
3. Age ≥18 years
4. Hemoglobin A1c ≥48 mmol/mol
5. Stable glucose-lowering treatment for 60 days prior to screening visit
6. Treatment with at least one glucose-lowering drug (in a fixed dose)

Exclusion criteria 11

1. Breast feeding, pregnancy or intention to become pregnant
2. Not using adequate contraceptive methods if woman of child-bearing potential (intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections))
3. History of acute and/or chronic pancreatitis
4. Liver disease and/or alanine transaminase (ALT) and/or aspartate transaminase (AST) >2x upper normal serum levels
5. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2
6. Anaemia (males blood haemoglobin <8.0 mmol/l and females <7.0 mmol/l)
7. Known allergic reaction to study drug (empagliflozin)
8. Treatment with an SGLT2-inhibitor within the last 60 days prior to screening visit
9. Inability (judged by investigator) or unwillingness (of the potential participant) to abstain from a variable dosing regimen of glucose-lowering drugs (i.e., SU, repaglinide or insulin (bolus insulin) in a self-titrated regimen) during the study.
10. Any concomitant disease or other condition(s) judged by investigators to be a safety concern or otherwise problematic for the conduct of the trial
11. Inability to complete the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean difference between empagliflozin and placebo in mean sensor glucose measured by continous glucose monitoring (CGM) during the last 10 or 14 (depending on CGM device) days of each treatment period evaluated in principal stratum.

Secondary endpoints 18

1. CGM: Coefficient of variation (CV%)
2. CGM: standard deviation
3. CGM: percentage of time in range (3.9–10 mmol/L)
4. CGM: percentage of time above range (>10 mmol/L)
5. CGM: percentage of time below <3.9 mmol/L
6. CGM: percentage of time below <3.0 mmol/L
7. Serum (or plasma) fructosamine
8. Serum (or plasma) glycated albumin
9. 24h urinary glucose excretion (24h UGE)
10. 24h renal threshold of glucose excretion (estimated using CGM and 24h UGE)
11. Fasting urinary glucose-to-creatine-ratio
12. Fasting ketone level (self-measured, before clinical visits)
13. Fasting capillary blood glucose (self-measured, before clinical visits)
14. Body weight
15. Number of hypoglycaemic events and participants with events measured by CGM stratified by severity (level 1, 2, and 3)
16. Number of hypoglycaemic events reported by participants stratified by severity (level 1, 2, and 3)
17. Number of participants with fasting ketone levels ≥0.6 mmol/l
18. Number of participants with fasting ketone levels ≥1.5 mmol/l

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Steno Diabetes Center Copenhagen

Sponsor organisation

Steno Diabetes Center Copenhagen

Address

Borgmester Ib Juuls Vej 83

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Steno Diabetes Center Copenhagen

Contact name

Tina Vilsbøll

Public contact point

Organisation

Steno Diabetes Center Copenhagen

Contact name

Henrik Maagensen

Third parties 1

Locations

1 EU/EEA country · 2 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

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

Application history

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