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

Launched by THE METHODIST HOSPITAL RESEARCH INSTITUTE · Mar 8, 2022

Keywords

ClinConnect Summary

Prevention of, or slowing the progression of, the development of allograft fibrosis has not been successful in previous efforts. This study will to evaluate the potential of fingolimod (Gilenya®, Novartis Pharmaceuticals, East Hanover, NJ) (1), a sphingosine 1-phosphate receptor modulator and a RhoA inhibitor (2), to abrogate the presence of interstitial fibrosis/tubular atrophy (IF/TA) after kidney transplantation. The study may provide important information for future clinical trials for prevention of IF/TA in kidney transplant recipients.

Interstitial fibrosis and tubular atrophy almost...

Gender

ALL

Eligibility 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.