Can Dapagliflozin Preserve Structure and Function in Transplanted Kidneys?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

6 Jun 2024 → ongoing

Decision date (initial)

2024-06-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Norwegian Research Council · AstraZeneca · Norwegian Health Region South-East

External identifiers

EU CT number

2023-510485-27-00

EudraCT number

2022-002428-10

ClinicalTrials.gov

NCT05788276

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To show that the yearly loss of renal function measured by
estimated GFR from plasma creatinine concentrations over time (eGFR slope) is
reduced with the SGLT2 inhibitor dapagliflozin versus placebo.

Secondary objectives 2

1. Treatment with the SGLT2 inhibitor dapagliflozin over time may reduce the degree of inflammation, fibrosis and vasculopathy in renal kidney grafts, and change footprints of degenerative pathways visualized by mRNA sequencing and proteomics analyses in the biopsies.
2. Treatment with dapagliflozin may reduce overweight and abdominal fat mass, together with improved glucose tolerance, blood pressure and urinary protein excretion in kidney transplant recipients

Conditions and MedDRA coding

Kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Renal transplant recipients transplanted 6 (±2) weeks earlier at OUH Rikshospitalet.
2. Age 18-75 years.
3. Able to comply with the medical treatment on their own.
4. Calcineurin inhibitor trough concentrations in accordance with individual therapeutic range and standard dose prednisolone and mycophenolate mofetil over the last 2 weeks.
5. Estimated GFR (EKFC-formula) ≥25 mL/min/1.73 m2.

Exclusion criteria 7

1. Type 1 diabetes.
2. Rejection episodes of the kidney graft prior to randomization.
3. Ongoing infectious disease or intermittent causes affecting renal function, e.g. untreated obstructive lymphocele.
4. Malnutrition.
5. Urosepsis less than 1 year prior to randomization.
6. Participants with a known hypersensitivity to dapagliflozin or any of the excipients of the product.
7. Women who are breastfeeding, pregnant patients or women of childbearing potential (WOCBP) not on highly effective contraception (not acceptable methods: progesterone-only oral hormonal contraception, male/female condom without spermicide or cap, diaphragm or sponge with spermicide. See also section 6.8).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the difference in eGFR slope between groups from before randomization to 3 years after transplantation. The slope is to be determined by mixed model statistics including MDRD4 formula estimated GFR from at least four creatinine measurements per year.

Secondary endpoints 17

1. Difference between groups in the slope of urinary protein/creatinine ratio over the first 72 and 150 weeks of treatment, respectively, assessed from at least four urine samples per year using mixed model statistics.
2. Difference between groups in blood pressure from before to 72 and 150 weeks of treatment
3. Difference between groups in changes of measured GFR (iohexol serum clearance) from 2 weeks to 72 weeks and 150 weeks of treatment
4. Difference between groups in changes of DXA-measured percent subcutaneous and visceral fat in relation to total fat mass from 2 weeks to 72 weeks of treatment
5. Difference between groups in glucose tolerance assess by an oral glucose tolerance test before to 72 weeks of treatment
6. Difference between groups in urinary metabolomic profile from before to 72 weeks of treatment (explorative endpoint)
7. Difference between groups in number of patients with at least one biopsy proven acute rejection episode up to 150 weeks of treatment
8. Difference between groups in adverse events such as genital candida infections, lower urinary tract infections, ketoacidosis and Fourniers gangrene over the first 72 and 150 weeks of treatment, respectively
9. Difference between groups in selected clinical chemistry markers (hemoglobin, hematocrit, sodium, potassium, magnesium and uric acid) before, at 72 and at 150 weeks of treatment
10. Difference between groups in degree of change in inflammation-score (Immunohistochemistry analysis with regards to amount of collagen and extracellular markers.) in protocol biopsies from before to 72 weeks of treatment
11. Difference between groups in degree of change in fibrosis-score (Semi-quantitative estimation of percent graft fibrosis in the renal cortex) in protocol biopsies from before to 72 weeks of treatment
12. Difference between groups in changes in kidney graft mRNA and protein expression patterns from before to 72 weeks of treatment (explorative endpoint)
13. Difference between groups in the 10-year extended eGFR slope from annual plasma creatinine values reported to NRR after year 3
14. Difference between groups in incidence of graft loss (assessed from NRR) up to 10 years after transplantation
15. Difference between groups in incidence and time to cardiovascular events (from NRR, first of each type; coronary heart disease, cerebrovascular events, chronic heart failure) as assessed up to 10 years after transplantation
16. Changes in urinary tubulus biomarkers from before to 72 weeks
17. Difference between groups in urinary tubular function biomarker levels from before to 72 weeks of treatment (explorative endpoint)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Trond Jenssen

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Trond Jenssen

Locations

1 EU/EEA country · 1 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 3 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