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

Prior treatment

• Planned to commence kidney replacement therapy or kidney transplant surgery in next 6 months
• Recipient of kidney transplant
• 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.
• Current treatment with strong CYP3A4 inhibitors
• Systolic BP \<110 mmHg or diastolic BP\<55 mmHg without antihypertensive therapy at time of screening
• Recipient of kidney transplant
• 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
• Previous episode of pancreatitis
• 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).

Other illness

• Known allergy, intolerance or contraindication to MRAs
• Severe hepatic impairment (defined as Child-Pugh Class C)
• Adrenal insufficiency
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
• Personal or first-degree relative(s) with a history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC)
• Uncontrolled thyroid disease TSH\>6.0 mIU/L or \<0.4mlU/L
• Type 1 diabetes
• Known allergy, intolerance, or contraindication to GLP-1 RAs
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.

Lab values

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

Other

• 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
• Currently pregnant or breast feeding, or intending to become pregnant
  • GLP-1 RA Domain
• Currently pregnant or breast feeding, or intending to become pregnant or is of child-bearing potential, and not using a highly effective contraceptive method

• Age ≥ 18 years
• Known chronic kidney disease from any cause (eGFR ≥25 mL/min/1.73m2)
• Currently receiving standard of care treatment according to treating physician
• Eligible for randomisation in at least one recruiting domain-specific appendix
• Participant and treating physician are willing and able to perform trial procedures
• 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.
• 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.
• Treating physician believes finerenone is clinically appropriate for the participant.
• Participant and treating physician are willing and able to perform MRA DSA procedures.
• Provision of written informed consent or eConsent following a fully informed discussion and prior to performing any MRA DSA related procedures
• 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.
• 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.
• HbA1c less than or equal to 10% (less than or equal to 86mmol/L)
• BMI ≥23 kg/m2 and \< 50 kg/m2
• Treating physician believes semaglutide is clinically appropriate for the participant
• Participant and treating physician are willing and able to perform GLP-1 RA DSA procedures
• Provision of written informed consent or eConsent following a fully informed discussion and prior to performing any GLP-1 RA DSA related procedures