Fingolimod for the Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation

• Status: Not yet recruiting
• Trial end date: 2025-06-15
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized, double-blind, placebo-controlled trial in de novo kidney transplant patients to determine if the addition of fingolimod (brand name Gilenya®, candidate name- FTY720) on the background of standard immunosuppression will prevent expansion of the interstitial compartment of the transplanted kidney. Interstitial expansion is the precursor of interstitial fibrosis and graft loss. We hypothesize that abgrogating the fibrogenic effects of both the RhoA and mTOR pathways with fingolimod will reduce structural damage in transplanted kidneys and possible subsequent transplant failure.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Methodist Hospital Research Institute
• Treatments: Fingolimod Hydrochloride

Criteria

Inclusion Criteria:

• Provision of signed and dated informed consent form

• Stated willingness to comply with all study procedures and availability for the duration of the study

• Receiving a first or second kidney transplant

• Male or female, aged ≥18 to ≤65

• Women of child bearing potential who have a negative serum pregnancy test prior to treatment

• Women of child bearing potential (including perimenopausal women who have had a menstrual period within the previous 1 year) who agree to use 2 forms of effective birth control regimen (at least one of which is a barrier method) throughout the study period and for 6 weeks following the end of the study or the last dose of mycophenolic acid, whichever comes first.

• Panel of reactive antibodies <50%

• Able to take oral medication

• Agreement to adhere to Lifestyle Considerations throughout study duration: refraining from the consumption of grapefruit or grapefruit juice and stopping any anticoagulation therapy, including ASA, one week prior and one week post kidney biopsy procedure

Exclusion Criteria:

• Transplantation of any organ other than kidney

• History or presence of second degree AV block, third degree AV block, symptomatic bradycardia, or an arrhythmia requiring current treatment with Class Ia or III antiarrhythmic drugs.

• Heart rate <60 beats per minute

• Presence of an increased QTc interval > 500 ms on screening ECG.

• Presence of a cardiac pacemaker.

• History of any major cardiac events, including heart attack within the last six months of enrollment, unstable angina, congestive heart failure, or any severe cardiac disease as determined by investigator

• Known macular degeneration

• Diagnosed with any significant coagulopathy or medical condition requiring long-term systemic anticoagulation after transplantation, which would interfere with obtaining biopies.

• Diagnosed with chronic immune system disease

• Diagnosed with acute pulmonary disease

• Diagnosed with severe liver disease, including abnormal liver enzymes or total bilirubin greater than three times upper limit of normal.

• Diagnosed with any past or present malignancies except squamous or basal cell carcinoma of the skin excised at least two years prior to randomization.

• Diagnosed with active acute or chronic infection, or febrile illness within two weeks prior to randomization.

• Recent history of strokes in the preceding 6 months

• Use of ketoconazole for more than 2 weeks

• Use of any investigational drug during the 4 weeks prior to enrolling in this study

• Women of child bearing potential who are breastfeeding

• Women of childbearing potential not practicing reliable methods of contraception. Reliable methods for contraception include surgical sterilization (hysterectomy, bilateral tubal ligation), double-barrier method (such as condom and diaphragm). To be considered as post-menopausal and not of childbearing potential, female participants must have experienced 12 consecutive months of amenorrhea.

• Known allergic reactions to components of Gilenya®, specifically fingolimod, gelatin, magnesium stearate, mannitol, titanium dioxide, and/or yellow iron oxide

• Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements.