Fingolimod for Kidney Transplant Rejection

Overseen By Darrel Cleere, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Immunosuppressants

Must not be taking: Class Ia or III antiarrhythmics, Ketoconazole

Disqualifiers: Cardiac disease, Liver disease, Malignancies, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 183

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fingolimod (also known as Gilenya or Tascenso ODT) can prevent problems in transplanted kidneys. Specifically, it aims to stop scarring that can lead to kidney failure. Participants will take either fingolimod or a placebo (a pill with no active medicine) for three months. Those who have just received their first or second kidney transplant might be suitable, provided they have no serious heart conditions or other major health issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop any anticoagulation therapy, including aspirin, one week before and after a kidney biopsy. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that fingolimod is likely to be safe for humans?

Research shows that fingolimod, the treatment under study, has some safety information available. In earlier studies, some patients experienced changes in liver enzymes, but these levels usually returned to normal after stopping the medication. Fingolimod might also increase the risk of bacterial or viral infections.

Fingolimod is already approved for other uses, such as treating multiple sclerosis, providing some insight into its safety profile. However, this trial is a Phase 2 study, primarily aiming to assess the drug's efficacy and safety for this new use in kidney transplant patients. While some safety information exists, researchers are still exploring its effects in this specific context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for kidney transplant rejection focus on suppressing the immune system to prevent it from attacking the transplanted organ. However, Fingolimod works differently by specifically targeting and trapping certain white blood cells (lymphocytes) in the lymph nodes, preventing them from reaching the kidney and causing damage. This unique mechanism reduces the risk of transplant rejection without broadly suppressing the immune system, potentially leading to fewer side effects. Researchers are excited about Fingolimod because it offers a more targeted approach, which could improve the long-term success of kidney transplants.

What evidence suggests that fingolimod might be an effective treatment for kidney transplant rejection?

Previous studies have shown that fingolimod holds promise in preventing acute rejection in kidney transplant patients. This trial will compare fingolimod with a placebo to evaluate its effectiveness. Fingolimod adjusts the immune system to protect the transplanted kidney. Research indicates that fingolimod targets two pathways, RhoA and mTOR, which can harm kidney tissues. By blocking these pathways, fingolimod may help reduce damage and prevent kidney transplant failure. These findings suggest that fingolimod could effectively maintain kidney health after a transplant. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults aged 18-65 who are receiving their first or second kidney transplant can join this trial. They must be able to take oral medication, have a low level of antibodies, and agree to use two forms of birth control if applicable. People with heart issues, severe liver disease, recent strokes, certain infections or cancers (except some skin cancers), or those on anticoagulants cannot participate.

Inclusion Criteria

I am getting my first or second kidney transplant.

Provision of signed and dated informed consent form

I agree not to eat grapefruit or drink its juice and to stop blood thinners one week before and after a kidney biopsy.

Exclusion Criteria

I have severe liver disease with high liver enzyme or bilirubin levels.

I have had cancer before, but it was not skin cancer removed over two years ago.

I have been diagnosed with macular degeneration.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 0.5 mg/day of fingolimod or placebo for 3 months

12 weeks

Visits at baseline, 3, 14, 30, 90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Visits at 180, 270, and 365 days

What Are the Treatments Tested in This Trial?

Interventions

• Fingolimod
• Placebo

Trial Overview The trial is testing whether Fingolimod added to standard immunosuppression can prevent damage in transplanted kidneys by stopping fibrosis from developing. Participants will either receive Fingolimod or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Fingolimod Active Control 1 Intervention

Participants will take a 0.5 mg fingolimod capsule each day for 3 months. The fingolimod capsule will be placed inside an opaque closed gelatin capsule without transformation of the manufacteror's fingolimod capsule. The fingolimod blinded product and the placebo capsule will be identical in size, color, appearance, and weight.

Group II: Placebo Placebo Group 1 Intervention

Participants will take a placebo capsule daily for 3 months. Placebo will be methylcellulose encapsulated into an opaque closed gelatin capsule for blinding. Capsules will be placed in a labeled bottle, with the contents only identifiable by a code on the package label and only the compounding pharmacy and the unblinded pharmacist at Houston Methodist Investigational Drug Service will know the code definition.

Fingolimod is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Gilenya for:

• Relapsing forms of multiple sclerosis

Approved in United States as Gilenya for:

• Relapsing forms of multiple sclerosis

Approved in Canada as Gilenya for:

• Relapsing forms of multiple sclerosis

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Fingolimod is an effective oral treatment for relapsing forms of multiple sclerosis, showing significant reductions in relapse rates and MRI progression compared to placebo and other treatments like IFN-β.

While generally well tolerated, fingolimod can cause common side effects such as fatigue and headaches, and rare but serious risks like heart issues and infections, necessitating careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis. Ward, MD., Jones, DE., Goldman, MD.[2015]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4853966/

Effect of FTY720 (fingolimod) on graft survival in renal ... The results of some clinical trials have demonstrated that FTY720 has promising efficacy for preventing acute rejection in de novo renal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6392001/

Fingolimod: Lessons Learned and New Opportunities for ... FTY720 was pursued clinically as a novel immunosuppressive agent suitable for reducing rejection in organ transplantation based on multiple animal models, ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/pediatric/276_22527S024-fingolimod-clinical-both.pdf

CLINICAL REVIEW - accessdata.fda.gov ... effects), a higher percentage of renal transplant patients who received fingolimod experienced a seizure, compared with patients in the ...

4. tascenso.com tascenso.com/hcp/what-is-tascenso-odt/bioequivalence/

Efficacy and Safety The majority occurred within 6 to 9 months and returned to normal within 2 months after discontinuing fingolimod. Recurrence of liver transaminase elevations ...

5. ema.europa.eu ema.europa.eu/en/documents/product-information/gilenya-epar-product-information_en.pdf

Gilenya, INN-fingolimod - European Medicines Agency Pharmacokinetic data were obtained in healthy adult volunteers, in renal transplant adult patients and in multiple sclerosis adult patients. The ...