Finerenone for Kidney Transplant Recipients
Recruiting in Palo Alto (17 mi)
Overseen byAmy Mottl, MD, MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of North Carolina, Chapel Hill
Must not be taking: Spironolactone, Eplerenone, Sacubitril/valsartan, others
Disqualifiers: Lupus nephritis, ANCA vasculitis, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?
EFFEKTOR is a vanguard, multicenter, phase 2 randomized, double blinded, placebo controlled clinical trial to determine the feasibility, tolerability, safety, and efficacy of finerenone in kidney transplant recipients (KTRs). One hundred fifty (150) KTRs will be randomized in a 2:1 ratio of finerenone to placebo, with two embedded substudies: (i) a kidney biopsy substudy in 50 participants who undergo a research kidney biopsy prior to randomization and at the end of active treatment; and (ii) a functional MRI (fMRI) substudy in 50 participants who undergo fMRI prior to randomization and at the end of active treatment.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, such as spironolactone, eplerenone, sacubitril/valsartan, potassium-sparing diuretics, and some blood pressure medications, at least 2 weeks before screening. You also need to stop using certain enzyme-affecting drugs at least 7 days before randomization.
What data supports the effectiveness of the drug Finerenone for kidney transplant recipients?
How is the drug Finerenone unique for kidney transplant recipients?
Finerenone is unique because it is a non-steroidal mineralocorticoid receptor antagonist, which means it works differently from traditional immunosuppressive drugs used in kidney transplants that often involve steroids or calcineurin inhibitors. This could potentially reduce the side effects associated with these other treatments.678910
Eligibility Criteria
The EFFEKTOR study is for adult kidney transplant recipients who are 1 to 10 years post-transplant with a certain level of protein in their urine and stable kidney function. Participants must agree to use contraception if of childbearing potential, or be confirmed not of childbearing potential.Inclusion Criteria
I received a kidney transplant between 1 and 10 years ago.
My kidney transplant is functioning well, as per my doctor's assessment.
Females of reproductive age must have a negative pregnancy test prior to enrollment and agree to use an intrauterine device, implant or combined oral contraceptive with a physical barrier (e.g., condom) throughout the study period and for 8 weeks following the last intervention dose.
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Exclusion Criteria
UACR >3500 mg/g at screening. This may be reassessed if one of the three first morning urine samples is >3500 mg/g at the screening visit
Known hypersensitivity to the study treatment
I need treatment with a steroidal MRA.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive finerenone or placebo with dose titration based on potassium levels
12 months
Regular visits for dose titration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Kidney Biopsy Substudy
Participants undergo kidney biopsy before randomization and at the end of active treatment
12 months
Functional MRI Substudy
Participants undergo fMRI before randomization and at the end of active treatment
12 months
Treatment Details
Interventions
- Finerenone (Mineralocorticoid Receptor Antagonist)
- Placebo (Other)
Trial OverviewThis trial tests the safety and effectiveness of finerenone compared to a placebo in people who have received a kidney transplant. It includes special substudies involving kidney biopsies and functional MRI scans before treatment starts and after it ends.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: FinerenoneExperimental Treatment1 Intervention
Participants in this study arm will receive the study drug Finerenone.
Initial Dosing: Dosing regimen of 10 mg or 20 mg once daily (QD), based upon screening eGFR. For eGFR \< 60 mL/min/1.73m\^2, participants will start at 10 mg QD. For eGFR ≥ 60 mL/min/1.73m\^2, participants will start at 20 mg QD.
Dose Titration: Dose will be titrated according to potassium levels. For participants initiated at 10mg, the dose will be up titrated to 20 mg if the potassium level measured after 2 weeks is ≤4.8 meq/L and eGFR has not decreased by \>30 percent of the screening visit value. Study drug dosing may be titrated up or down per the below.
Potassium level: ≤ 4.8
* If on lower dose, up-titrate to higher dose
* If on higher dose, continue on the same dose
Potassium level: 4.9-5.5 = continue same dose
Potassium level: \>5.5 = withhold study drug and recheck potassium within 3 days. Re-initiate study drug at the 10 mg dose once potassium is ≤4.8 meq/L.
Group II: PlaceboPlacebo Group1 Intervention
Participants in this study arm will receive the placebo comparator.
Initial Dosing: Dosing regimen of 10 mg or 20 mg once daily (QD), based upon screening eGFR. For eGFR \< 60 ml/min/1.73m\^2, participants will start at 10mg QD. For eGFR ≥ 60ml/min/1.73m\^2, participants will start at 20 mg QD.
Dose Titration: Dose will be titrated according to potassium levels. For participants initiated at 10 mg, the dose will be up titrated to 20 mg if the potassium level measured after 2 weeks is ≤4.8 meq/L and eGFR has not decreased by \>30 percent of the screening visit value. Study drug dosing may be titrated up or down per the table below.
Potassium level: ≤ 4.8
* If on lower dose, up-titrate to higher dose
* If on higher dose, continue on the same dose
Potassium level: 4.9-5.5 = continue same dose
Potassium level: \>5.5 = withhold study drug and recheck potassium within 3 days. Re-initiate study drug at the 10 mg dose once potassium is ≤4.8 meq/L.
Finerenone is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Kerendia for:
- Chronic kidney disease associated with type 2 diabetes
🇪🇺 Approved in European Union as Kerendia for:
- Chronic kidney disease associated with type 2 diabetes
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UNC Eastowne Kidney Transplant ClinicChapel Hill, NC
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Who Is Running the Clinical Trial?
University of North Carolina, Chapel HillLead Sponsor
BayerIndustry Sponsor
References
Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study. [2023]Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes.
Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial. [2023]Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD.
Finerenone in Hispanic Patients With CKD and Type 2 Diabetes: A Post Hoc FIDELITY Analysis. [2023]In FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes. This analysis explores the efficacy and safety of finerenone in Hispanic patients.
Finerenone in diabetic kidney disease: A systematic review and critical appraisal. [2022]Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes (T2D). We aim to conduct a systematic review of finerenone to know the efficacy and safety of finerenone in CKD with or without T2D.
Finerenone Dose-Exposure-Serum Potassium Response Analysis of FIDELIO-DKD Phase III: The Role of Dosing, Titration, and Inclusion Criteria. [2022]Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist (MRA) that demonstrated efficacy in delaying the progression of chronic kidney disease (CKD) and reducing cardiovascular events in patients with CKD and type 2 diabetes mellitus in FIDELIO-DKD, where 5734 patients were randomized 1:1 to receive either finerenone or placebo, with a median follow-up of 2.6 years. Doses of finerenone 10 or 20 mg once daily were titrated based on (serum) potassium and estimated glomerular filtration rate. The MRA mode of action increases potassium.
Medication errors and adverse drug events in kidney transplant recipients: incidence, risk factors, and clinical outcomes. [2022]To determine the incidence, risk factors, and clinical outcomes associated with clinically significant medication errors or adverse drug events in kidney transplant recipients.
Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials. [2022]We combined the outcomes of all randomised controlled trials to investigate the safety and efficacy of steroid avoidance or withdrawal (SAW) regimens in paediatric kidney transplantation compared with steroid-based (SB) regimens.
Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review. [2022]A simplified dosing regimen may improve drug compliance in kidney transplant recipients and long-term graft outcomes. We aimed to identify, appraise, and synthesize the current evidence comparing the relative safety and efficacy of the recently introduced daily versus standard twice-daily tacrolimus administration.
Novel immunosuppressive agents in kidney transplantation. [2021]Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.
A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation. [2009]This longitudinal, sequential, matched closed-cohort design pharmacoepidemiological analysis examined the influence of maintenance steroid therapy in 380 first graft recipients after renal transplantation under conditions of normal clinical practice.