Finerenone for Kidney Transplant Recipients

Overseen By Sara Kelley, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

150 Participants Needed

What You Need to Know Before You Apply

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.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Finerenone for kidney transplant recipients?

Finerenone has been shown to improve kidney and heart health in patients with chronic kidney disease and type 2 diabetes, suggesting it may help protect kidney function in other conditions as well. ^{6 7 8 9 10}

Who Is on the Research Team?

Amy Mottl, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Prabir Roy-Chaudhury, MD, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Finerenone
• Placebo

Trial Overview This 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.

How Is the Trial Designed?

Group I: Finerenone Experimental Treatment 1 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: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a study of 5,674 patients with chronic kidney disease and type 2 diabetes, finerenone significantly reduced the risk of kidney and cardiovascular complications, regardless of baseline HbA1c levels or insulin use.

The treatment was well-tolerated, with similar rates of adverse events between finerenone and placebo groups, indicating its safety profile, particularly with low discontinuation rates due to hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Rossing, P., Burgess, E., Agarwal, R., et al.[2023]

In the FIDELIO-DKD trial, 21.4% of patients treated with finerenone experienced mild hyperkalemia compared to 9.2% in the placebo group, indicating a higher risk of elevated potassium levels with finerenone.

Despite the increased risk of hyperkalemia associated with finerenone, effective monitoring and management strategies were implemented, which helped minimize its impact and support the safe clinical use of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial. Agarwal, R., Joseph, A., Anker, SD., et al.[2023]

In a study of 13,026 patients with chronic kidney disease (CKD) and type 2 diabetes, finerenone showed similar efficacy in reducing cardiovascular and kidney-related events in Hispanic patients compared to non-Hispanic patients, with a notable 20% reduction in cardiovascular events for those on finerenone.

Finerenone also significantly reduced urinary albumin-to-creatinine ratio (UACR) by 32% at month 4 in both Hispanic and non-Hispanic patients, indicating its effectiveness in improving kidney function, while maintaining a similar safety profile across both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone in Hispanic Patients With CKD and Type 2 Diabetes: A Post Hoc FIDELITY Analysis. Rosas, SE., Ruilope, LM., Anker, SD., et al.[2023]

Finerenone, a new non-steroidal mineralocorticoid antagonist, shows better renal outcomes compared to spironolactone and improved mortality outcomes compared to eplerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), with fewer instances of hyperkalemia.

In long-term studies, finerenone significantly reduces the progression of renal disease and cardiovascular events, particularly heart failure hospitalizations, without affecting HbA1c, body weight, or causing sexual side effects, although it does have a higher rate of hyperkalemia leading to drug withdrawal compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone in diabetic kidney disease: A systematic review and critical appraisal. Singh, AK., Singh, A., Singh, R., et al.[2022]

Finerenone, a selective mineralocorticoid receptor antagonist, effectively delays chronic kidney disease progression and reduces cardiovascular events in patients with CKD and type 2 diabetes, based on a study of 5734 patients over a median follow-up of 2.6 years.

The study's pharmacokinetic analysis showed that while potassium levels decreased with higher doses of finerenone, careful dose titration based on potassium levels can safely manage this effect, ensuring that the risk of hyperkalemia remains comparable to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone Dose-Exposure-Serum Potassium Response Analysis of FIDELIO-DKD Phase III: The Role of Dosing, Titration, and Inclusion Criteria. Goulooze, SC., Snelder, N., Seelmann, A., et al.[2022]

In a study of 476 kidney transplant recipients, 8% experienced clinically significant medication errors, which were linked to higher rates of acute rejection, infections, and readmissions.

Risk factors for these medication errors included being female, African-American, having pretransplant diabetes, experiencing delayed graft function, and being a retransplant recipient, highlighting the need for targeted interventions in these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication errors and adverse drug events in kidney transplant recipients: incidence, risk factors, and clinical outcomes. Taber, DJ., Pilch, NA., Bratton, CF., et al.[2022]

In a systematic review of 5 randomized controlled trials involving 528 pediatric kidney transplant patients, steroid avoidance or withdrawal (SAW) regimens significantly improved post-transplant growth, as indicated by an increase in height standardised Z-score (ΔHSDS) especially within the first year after withdrawal.

The SAW regimen did not increase the risk of acute rejection compared to steroid-based regimens, suggesting it can be safely implemented in select pediatric patients without compromising graft function or survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials. Zhang, H., Zheng, Y., Liu, L., et al.[2022]

A systematic review of 21 studies involving 5,385 kidney transplant recipients found that once-daily tacrolimus is as effective as the standard twice-daily regimen in preventing acute rejection and ensuring patient and graft survival over 12 months.

There were no significant differences in key outcomes such as biopsy-proven acute rejection, patient survival, or graft survival between the two dosing regimens, suggesting that a simplified once-daily dosing may improve compliance without compromising safety or efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review. Ho, ET., Wong, G., Craig, JC., et al.[2022]

Contemporary immunosuppressive regimens for renal transplantation have significantly reduced acute rejection rates, but challenges like chronic allograft injury and adverse events remain, highlighting the need for improved therapies.

Investigational agents such as ASKP1240, a fully-human anti-CD40 monoclonal antibody, and alternatives to calcineurin inhibitors like belatacept and voclosporin are being explored to enhance graft outcomes while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel immunosuppressive agents in kidney transplantation. Hardinger, KL., Brennan, DC.[2021]

In a study of 380 kidney transplant recipients, avoiding maintenance steroid therapy did not negatively affect graft function or increase the rate of acute rejection over two years, suggesting that steroid avoidance can be a safe option.

Patients who avoided steroids experienced lower cholesterol levels and weight gain compared to those who received steroids, indicating potential additional health benefits from steroid avoidance in the context of renal transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation. Barraclough, KA., Landsberg, DN., Shapiro, RJ., et al.[2009]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

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]

2. United States pubmed.ncbi.nlm.nih.gov

Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Finerenone in Hispanic Patients With CKD and Type 2 Diabetes: A Post Hoc FIDELITY Analysis. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Finerenone in diabetic kidney disease: A systematic review and critical appraisal. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Finerenone Dose-Exposure-Serum Potassium Response Analysis of FIDELIO-DKD Phase III: The Role of Dosing, Titration, and Inclusion Criteria. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Medication errors and adverse drug events in kidney transplant recipients: incidence, risk factors, and clinical outcomes. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Novel immunosuppressive agents in kidney transplantation. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation. [2009]