The Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect

1. Age ≥ 18 years

2. Known chronic kidney disease from any cause (eGFR ≥25 mL/min/1.73m2)

3. Currently receiving standard of care treatment according to treating physician

4. Eligible for randomisation in at least one recruiting domain-specific appendix

5. Participant and treating physician are willing and able to perform trial procedures

1. Planned to commence kidney replacement therapy or kidney transplant surgery in next 6 months

2. Life expectancy less than 6 months

To be included in any of the following DOMAINS the participant must met eligible for the PLATFORM (as listed above)

MRA domain

Inclusion Criteria:

1. Urine albumin-creatinine ratio (uACR) >200 mg/g (22.6 mg/mmol) or urine protein-creatinine ratio (uPCR) >300 mg/g (33.9 mg/mmol) at time of screening.

2. On a stable standard of care treatment for CKD, including a SGLT2i unless there is a documented reason not to be using a SGLT2i*, for 4 weeks before screening according to treating physician.

3. Treating physician believes finerenone is clinically appropriate for the participant.

4. Participant and treating physician are willing and able to perform MRA DSA procedures.

5. Provision of written informed consent or eConsent following a fully informed discussion and prior to performing any MRA DSA related procedures

Exclusion Criteria:

1. Recipient of kidney transplant

2. Hyperkalaemia (serum potassium ≥5.0 mmol/L) at time of screening

3. Current treatment with MRA, where the treating physician or patient is not willing to discontinue this medication. If willing to discontinue the MRA, the potential participant must be re-screened after they have been on stable standard of care treatment for 4 weeks without the MRA.

4. Known allergy, intolerance or contraindication to MRAs

5. Current treatment with strong CYP3A4 inhibitors

6. Systolic BP <110 mmHg or diastolic BP<55 mmHg without antihypertensive therapy at time of screening

7. Severe hepatic impairment (defined as Child-Pugh Class C)

8. Adrenal insufficiency

9. Currently pregnant or breast feeding, or intending to become pregnant

GLP-1 RA Domain

Inclusion Criteria

1. Urine albumin-creatinine ratio (uACR) >200 mg/g (22.6 mg/mmol) or urine proteincreatinine ratio (uPCR) >300 mg/g (33.9 mg/mmol) at time of screening.

2. On a stable standard of care treatment for CKD, including a SGLT2i and maximum tolerated ACEi/ARB unless there is a documented reason not to be using a SGLT2i, for 4 weeks before screening.

3. HbA1c less than or equal to 10% (less than or equal to 86mmol/L)

4. BMI ≥23 kg/m2 and < 50 kg/m2

5. Treating physician believes semaglutide is clinically appropriate for the participant

6. Participant and treating physician are willing and able to perform GLP-1 RA DSA procedures

7. Provision of written informed consent or eConsent following a fully informed discussion and prior to performing any GLP-1 RA DSA related procedures

Exclusion Criteria

1. Recipient of kidney transplant

2. Major adverse cardiovascular events (MACE), consisting of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death, within 90 days prior to the day of screening

3. Presently classified as being in New York Heart Association (NYHA) Class IV heart failure

4. Personal or first-degree relative(s) with a history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC)

5. Previous episode of pancreatitis

6. Uncontrolled thyroid disease TSH>6.0 mIU/L or <0.4mlU/L

7. Type 1 diabetes

8. Current treatment with a GLP-1 RA, where it is in the participant's best interests to continue the GLP-1 RA or where the treating physician or patient is not willing to discontinue this medication for a minimum of 4 weeks prior to randomisation and for the full duration of the trial (ie. 108 weeks if assigned to placebo).

9. Known allergy, intolerance, or contraindication to GLP-1 RAs

10. Currently pregnant or breast feeding, or intending to become pregnant or is of child-bearing potential, and not using a highly effective contraceptive method

11. Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.