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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if fingolimod can help new kidney transplant patients by preventing kidney damage and improving transplant success. Fingolimod works by blocking harmful pathways in the body. The study aims to see if this treatment is safe and effective over time. Fingolimod has been used in multiple sclerosis treatment and is known for its immunomodulating effects, but it has significant potential side effects.

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.

What data supports the effectiveness of the drug Fingolimod for kidney transplant rejection?

Fingolimod, when combined with other drugs like cyclosporine, has shown potential in preventing acute rejection in kidney transplant patients, as seen in studies where it was used as part of a combination therapy. ^{1 2 3 4 5}

How does the drug fingolimod differ from other treatments for kidney transplant rejection?

Fingolimod is unique because it is an oral medication that works by trapping immune cells in the lymph nodes, preventing them from attacking the transplanted kidney. This mechanism is different from the standard immunosuppressive drugs used in kidney transplants, which often involve a combination of drugs like calcineurin inhibitors and glucocorticoids. ^{5 6 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Exposure-efficacy relationships of a fingolimod-everolimus regimen in kidney transplant patients at risk for delayed graft function. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Novel immunosuppressive agents in kidney transplantation. [2021]

3. England pubmed.ncbi.nlm.nih.gov

FTY720 combined with tacrolimus in de novo renal transplantation: 1-year, multicenter, open-label randomized study. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Immunosuppressive strategies to improve outcomes of kidney transplantation. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

[Modern immunosuppression following renal transplantation. Standard or tailor made?]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence Study of 2 Capsule Formulations of Fingolimod 0.5 mg Assessing Both Parent Drug and Active Metabolite in New Zealand Healthy Subjects (Truncated Design). [2021]

8. England pubmed.ncbi.nlm.nih.gov

Delayed fingolimod-associated asystole. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Fingolimod for Relapsing-Remitting Multiple Sclerosis: The Experience From Saudi Arabia. [2021]