Clinical validation study of urinary clusterin and EGF in patients with chronic kidney disease

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

Not possible to specify

Decision date (initial)

2024-06-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Horizon Europe (Grant agreement ID: 101095146)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To compare the effect of a biomarker response guided treatment approach versus guideline care on albuminuria

Secondary objectives 3

1. To compare the effect of a biomarker response guided treatment approach versus guideline care on eGFR (surrogate endpoint for long-term kidney failure).
2. Establish a communication framework to educate study participants about their drug response and therapy decisions. CKD- bioMATCH will develop effective communication tools to inform study participants and CKD-bioMatch investigators about decisions to continue or change treatments based on the integrated biomarker responses. An integrated team of health counselors, nephrologists, and a patient advisory panel will develop health communication tools and assess their effectiveness and impact.
3. To compare the effect of a biomarker response guided treatment approach versus guideline care on the KidneyIntelX score (surrogate endpoint for treatment response).

Conditions and MedDRA coding

Chronic kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 and ≤ 75 years
2. eGFR ≥ 25 mL/min/1.73m2
3. UACR > 100 mg/g (10 mg/mmol) in two consecutive first-morning void urine samples. UACR 80-100 mg/g is accepted if historical measurements are above 100 mg/g and if it cannot be explained by any new treatment.
4. Participants must be on a maximum tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least four weeks before enrollment.
5. Ability to communicate with the study staff and understand and sign the informed consent.

Exclusion criteria 22

1. Age < 18 years or > 75 years
2. Eligible to receive at least two of three study treatments. Participants meeting two or more of the following criteria will be excluded: a. Potassium > 5.0 mmol/L b. Heart failure NYHA class III or IV or NT-proBNP > 600 pg/ml c. Not a candidate for treatment with an SGLT2 inhibitor, e.g., due to contraindications (according to the Forxiga SmPC) or previously experienced side effects from an SGLT2 inhibitor.
3. NT-proBNP > 1200 pg/ml
4. Severe peripheral or facial edema (according to the investigator's opinion)
5. Diagnosis of unstable angina pectoris and/or myocardial infarction within the last six months.
6. Already receiving treatment with two of the three study drugs (for example, an SGLT2 inhibitor and finerenone).
7. Treatment with a potassium-sparing diuretic or a mineralocorticoid receptor antagonist, except for finerenone (e.g., spironolactone, eplerenone, or amiloride)
8. Elevated Alanine Aminotransferase (ALT) > 3 x upper normal limit, autoimmune hepatitis, and/or severe hepatic impairment (including but not limited to a history of hepatic encephalopathy, a history of esophageal varices or a history of portocaval shunt.)
9. Autosomal dominant or autosomal recessive polycystic kidney disease
10. Lupus nephritis or ANCA-associated vasculitis, or any other primary or secondary kidney disease requiring immunosuppressive therapy within 6 months prior to screening
11. Kidney transplant
12. Dialysis
13. Addison's disease
14. Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
15. Idiopathic pulmonary fibrosis
16. Type 1 diabetes
17. Known or suspected hypersensitivity to the study medications or related products
18. Presence or history of malignant neoplasms (except basal cell skin cancer or squamous cell skin cancer) within 5 years before screening.
19. Any other history, condition, therapy, or uncontrolled intercurrent illness that could, as judged by the investigator, affect participant safety or compliance with study requirements.
20. A female who is pregnant, breastfeeding, or intends to become pregnant, or women of childbearing potential (WOCBP) who are not using highly effective contraceptive methods.
21. A female who is pregnant, breastfeeding, or intends to become pregnant, or women of childbearing potential (WOCBP) who are not using highly effective contraceptive methods.
22. Participant in another intervention study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Between-group comparison of the change in albuminuria (UACR) from baseline (randomization) to week 36.

Secondary endpoints 3

1. Between-group comparison of the change in eGFR from 1) week 16 to week 64 2) baseline to week 64 3) baseline to week 66
2. To have developed a communication tool at the end of the study that can instruct patients and healthcare professionals about using biomarker-guided treatment.
3. Between-group comparison of the change in KidneyIntelX score from baseline to week 36.

Investigational products

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

Test 3

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

Peter Rossing

Public contact point

Organisation

Steno Diabetes Center Copenhagen

Contact name

Peter Rossing

Third parties 1

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Application history

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