RecruitingPhase 2NCT06059664

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

Sponsor

University of North Carolina, Chapel Hill

Enrollment

150 participants

Start Date

Apr 23, 2024

Study Type

INTERVENTIONAL

Conditions

Kidney Transplant; Complications

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria15

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

Exclusion Criteria19

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).
Participation in the MRI Study is excluded for certain pacemakers, electronic implants, shrapnel of the eye and certain types of aneurysm clips.
Any other history, condition, or therapy which could, in the opinion of the investigator, affect compliance with the study treatment and procedures
Close affiliation with the investigational site, investigators or staff
Simultaneous participation in another interventional trial within 30 days prior to randomization

Interventions

DRUGFinerenone Oral Tablet

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.

DRUGPlacebo