The EFfect of FinErenone in Kidney TransplantiOn Recipients: The EFFEKTOR Study

NCT06059664 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-1867
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplant; Complications

Keywords

Finerenone; Cardiovascular Outcomes; Albuminuria; eGFR decline; Congestive Heart Failure; Kidney biopsy; Functional MRI

Outcome Measures

Primary Outcomes (2)

• Feasibility of recruitment to the main clinical trial: Total number of participants who were eligible and enrolled in the main clinical trial

  Signed consent by 30 participants for the main clinical trial within 3 months of launching the full study protocol (date of first person randomized).

  Up to 3 months after launching the full study protocol

• Feasibility of recruitment to the kidney biopsy substudy: Total number of participants who were eligible and enrolled in the kidney biopsy substudy

  Signed consent by 10 participants for the biopsy substudy within 3 months of launching the full study protocol (date of first person randomized).

  Up to 3 months after launching the full study protocol

Secondary Outcomes (7)

• Relative tolerability of finerenone

  From randomization to last on study drug visit, approximately 12 months

• Risk for discontinuation of finerenone

  From randomization to last on study drug visit, approximately 12 months

• Overall safety of finerenone

  From randomization to last on study drug visit, approximately 12 months

• Adverse Event (AE) related to hyperkalemia

  From randomization to last on study drug visit, approximately 12 months

• Adverse Event (AE) related to acute kidney injury

  From randomization to last on study drug visit, approximately 12 months

Other Outcomes (4)

• Efficacy for functional Magnetic Resonance Imaging (fMRI) kidney oxygenation

  From within 2 weeks before randomization, within 2 weeks before last on study drug visit, up to 12.5 months

• Efficacy for functional Magnetic Resonance Imaging (fMRI) kidney perfusion

  From within 2 weeks before randomization, within 2 weeks before last on study drug visit, up to 12.5 months

• Efficacy for functional Magnetic Resonance Imaging (fMRI) kidney fibrosis

  From within 2 weeks before randomization, within 2 weeks before last on study drug visit, up to 12.5 months

Study Arms (2)

Finerenone

EXPERIMENTAL

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.

Drug: Finerenone Oral Tablet

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Finerenone Oral Tablet DRUG

Blinded study of finerenone vs. placebo in kidney transplant recipients. Participants will take finerenone or placebo once daily for 12 months. The drug will be up- or down-titrated according to potassium levels.

Also known as: Kerendia

Finerenone

Placebo DRUG

Blinded study of finerenone vs. placebo in kidney transplant recipients. Participants will take finerenone or placebo once daily for 12 months. The drug will be up- or down-titrated according to potassium levels.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult kidney transplant recipients ≥ 18 years
• to 10 years post kidney transplantation from a deceased or living donor
• Stable kidney allograft function (within 20% baseline eGFR) and based on the clinical judgement of the investigator
• Preserved kidney allograft function defined as an eGFR ≥ 25 mL/min/1.73 m
• Urine albumin:creatinine ratio (UACR) ≥30 ug/mg
• Ability of the participant, or their legally authorized representative, to provide informed consent
• Contraceptive requirements:
• Women of non-childbearing potential do not need to undergo pregnancy testing or agree to use adequate contraception. Non-childbearing potential is defined as documented hysterectomy, bilateral salpingectomy, oophorectomy or postmenopausal females (amenorrhea for 12 months without an alternative medical cause). A single high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state.
• Women of childbearing potential can only be included if a pregnancy test is negative at the screening visit and if they agree to use adequate contraception during the study and until 8 weeks after the last study intervention dose. Adequate contraception is defined as an intrauterine device, implant or combined oral contraceptive with a physical barrier (e,g., condom).
• Willingness to undergo research study biopsies at screening and following the 12 month treatment period
• Ability to safely discontinue antiplatelet or anticoagulant treatments
• No known intrinsic bleeding diathesis
• Hemoglobin \>9.0 g/dL; Platelets \> 100,000; International Normalised Ratio (INR) \<1.4 on the day of kidney biopsy
• Body mass index \<40
• Blood pressure controlled on the day of biopsy to \<160/90

You may not qualify if:

• Documented recurrent lupus nephritis, ANtineutrophilic Cytoplasmic Antibody (ANCA) vasculitis, membranoproliferative glomerulonephritis (including C3 glomerulopathy)
• History of solid organ transplantation other than kidney
• Acute kidney injury requiring dialysis within 6 months prior to screening
• Uncontrolled hypertension with a sitting Systolic Blood Pressure (SBP) ≥180 mmHg or Diastolic Blood Pressure (DBP) ≥100 mmHg
• Any indication for treatment with a steroidal MRA
• 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
• CV event within 3 months prior to screening (heart failure requiring acute care, myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, elective coronary artery bypass grafting)
• Elective percutaneous coronary intervention within 1 month prior to screening
• Known hypersensitivity to the study treatment
• Addison's disease
• Hepatic insufficiency classified as Child-Pugh C
• Pregnancy, breast feeding or intention to become pregnant
• Concomitant therapy with spironolactone, eplerenone, sacubitril/valsartan combination, or potassium-sparing diuretic which cannot be discontinued at least 2 weeks prior to screening
• Simultaneous use of Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB), without being able to discontinue one of these at least 2 weeks prior to screening
• Use of potent CYP3A4 inhibitors or inducers (to be stopped at least 7 days before randomization).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Bayer: collaborator
• Weill Medical College of Cornell University: collaborator
• University of Cincinnati: collaborator

Study Sites (1)

UNC Eastowne Kidney Transplant Clinic

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Related Publications (17)

• Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725-30. doi: 10.1056/NEJM199912023412303.

  PMID: 10580071 BACKGROUND

• Hart A, Lentine KL, Smith JM, Miller JM, Skeans MA, Prentice M, Robinson A, Foutz J, Booker SE, Israni AK, Hirose R, Snyder JJ. OPTN/SRTR 2019 Annual Data Report: Kidney. Am J Transplant. 2021 Feb;21 Suppl 2:21-137. doi: 10.1111/ajt.16502.

  PMID: 33595191 BACKGROUND

• Rangaswami J, Mathew RO, Parasuraman R, Tantisattamo E, Lubetzky M, Rao S, Yaqub MS, Birdwell KA, Bennett W, Dalal P, Kapoor R, Lerma EV, Lerman M, McCormick N, Bangalore S, McCullough PA, Dadhania DM. Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies. Nephrol Dial Transplant. 2019 May 1;34(5):760-773. doi: 10.1093/ndt/gfz053.

  PMID: 30984976 BACKGROUND

• Matas AJ, Humar A, Gillingham KJ, Payne WD, Gruessner RW, Kandaswamy R, Dunn DL, Najarian JS, Sutherland DE. Five preventable causes of kidney graft loss in the 1990s: a single-center analysis. Kidney Int. 2002 Aug;62(2):704-14. doi: 10.1046/j.1523-1755.2002.00491.x.

  PMID: 12110036 BACKGROUND

• Paraskevas S, Kandaswamy R, Humar A, Gillingham KJ, Gruessner RW, Payne WD, Najarian JS, Sutherland DE, Matas AJ. Risk factors for rising creatinine in renal allografts with 1 and 3 yr survival. Clin Transplant. 2006 Nov-Dec;20(6):667-72. doi: 10.1111/j.1399-0012.2006.00566.x.

  PMID: 17100713 BACKGROUND

• Morales JM, Marcen R, del Castillo D, Andres A, Gonzalez-Molina M, Oppenheimer F, Seron D, Gil-Vernet S, Lampreave I, Gainza FJ, Valdes F, Cabello M, Anaya F, Escuin F, Arias M, Pallardo L, Bustamante J. Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study. Nephrol Dial Transplant. 2012 Dec;27 Suppl 4(Suppl 4):iv39-46. doi: 10.1093/ndt/gfs544.

  PMID: 23258810 BACKGROUND

• Karthikeyan V, Karpinski J, Nair RC, Knoll G. The burden of chronic kidney disease in renal transplant recipients. Am J Transplant. 2004 Feb;4(2):262-9. doi: 10.1046/j.1600-6143.2003.00315.x.

  PMID: 14974949 BACKGROUND

• Knoll GA. Proteinuria in kidney transplant recipients: prevalence, prognosis, and evidence-based management. Am J Kidney Dis. 2009 Dec;54(6):1131-44. doi: 10.1053/j.ajkd.2009.06.031. Epub 2009 Sep 2.

  PMID: 19726115 BACKGROUND

• Lam NN, Tonelli M, Lentine KL, Hemmelgarn B, Ye F, Wen K, Klarenbach S. Albuminuria and posttransplant chronic kidney disease stage predict transplant outcomes. Kidney Int. 2017 Aug;92(2):470-478. doi: 10.1016/j.kint.2017.01.028. Epub 2017 Mar 31.

  PMID: 28366228 BACKGROUND

• Gaston RS, Fieberg A, Hunsicker L, Kasiske BL, Leduc R, Cosio FG, Gourishankar S, Grande J, Mannon RB, Rush D, Cecka JM, Connett J, Matas AJ. Late graft failure after kidney transplantation as the consequence of late versus early events. Am J Transplant. 2018 May;18(5):1158-1167. doi: 10.1111/ajt.14590. Epub 2017 Dec 5.

  PMID: 29139625 BACKGROUND

• Meier-Kriesche HU, Baliga R, Kaplan B. Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation. 2003 Apr 27;75(8):1291-5. doi: 10.1097/01.TP.0000061602.03327.E2.

  PMID: 12717218 BACKGROUND

• Lenihan CR, Liu S, Deswal A, Montez-Rath ME, Winkelmayer WC. De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes. Am J Kidney Dis. 2018 Aug;72(2):223-233. doi: 10.1053/j.ajkd.2018.01.041. Epub 2018 Mar 29.

  PMID: 29605378 BACKGROUND

• Awan AA, Niu J, Pan JS, Erickson KF, Mandayam S, Winkelmayer WC, Navaneethan SD, Ramanathan V. Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996-2014). Am J Nephrol. 2018;48(6):472-481. doi: 10.1159/000495081. Epub 2018 Nov 23.

  PMID: 30472701 BACKGROUND

• Gaston RS, Fieberg A, Helgeson ES, Eversull J, Hunsicker L, Kasiske BL, Leduc R, Rush D, Matas AJ; DeKAF Investigators*. Late Graft Loss After Kidney Transplantation: Is "Death With Function" Really Death With a Functioning Allograft? Transplantation. 2020 Jul;104(7):1483-1490. doi: 10.1097/TP.0000000000002961.

  PMID: 31568212 BACKGROUND

• Ying T, Shi B, Kelly PJ, Pilmore H, Clayton PA, Chadban SJ. Death after Kidney Transplantation: An Analysis by Era and Time Post-Transplant. J Am Soc Nephrol. 2020 Dec;31(12):2887-2899. doi: 10.1681/ASN.2020050566. Epub 2020 Sep 9.

  PMID: 32908001 BACKGROUND

• Vinson AJ, Matas A. Late Allograft Loss and Contemporary Cardiorenal Metabolic Therapies. J Am Soc Nephrol. 2025 Apr 7;36(8):1659-1667. doi: 10.1681/ASN.0000000726.

  PMID: 40193211 DERIVED

• Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.

  PMID: 39382091 DERIVED

Related Links

• USRDS Annual Data Report 2020
• Organ Procurement and Transplantation Network

MeSH Terms

Conditions

Albuminuria; Heart Failure

Interventions

finerenone; Sugars

Condition Hierarchy (Ancestors)

Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Amy Mottl, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Prabir Roy-Chaudhury, MD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Mottl, MD, MPH

CONTACT

919-445-2641; amy_mottl@med.unc.edu

Sara Kelley, MPH

CONTACT

919-445-2658; sara_kelley@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 100 kidney transplant recipients will be randomized in a 2:1 ratio to finerenone versus placebo, with an embedded biopsy substudy in 50 participants (25 finerenone/25 placebo) who undergo a research kidney biopsy prior to randomization and at the end of active treatment.

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 29, 2023
• Study Start: April 23, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: From 9 months through 36 months after publication
• Access Criteria: The investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with University of North Carolina (UNC).

Locations

US (1)