Extended Release Tacrolimus for Lung Transplant Complications

Overseen By Haley Hoy, PhD, NP

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Immunosuppressants

Must not be taking: Antivirals

Disqualifiers: Prior organ transplant, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 7 months

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using tacrolimus, a drug that prevents the body from rejecting a new lung after a transplant. The researchers aim to determine if the extended-release version of tacrolimus (Tacrolimus Extended Release Oral Tablet [Envarsus]) provides the same protection while being gentler on the kidneys compared to the regular version. Participants will receive either the regular or extended-release tacrolimus, along with other standard medications. This trial may suit individuals who have recently undergone a lung transplant and are receiving care at Vanderbilt University Medical Center. As an Early Phase 1 trial, this research focuses on understanding how the extended-release version works in people, offering participants a chance to contribute to groundbreaking insights.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, it focuses on using a specific form of tacrolimus, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that extended-release tacrolimus (LCP-tacrolimus) is generally safe and well-tolerated in kidney transplant patients. The FDA has approved it to help prevent organ rejection in these patients, indicating a known safety record in transplant situations. Studies have found that the body absorbs it better, resulting in lower peak blood levels, which may reduce side effects like tremors and headaches compared to the immediate-release version.

While information is limited for lung transplants, several case reports indicate that patients who switched from the immediate-release to the extended-release form due to side effects or absorption issues tolerated it well. This suggests that LCP-tacrolimus might be a safer option for lung transplant patients needing strong immune system suppression, while potentially reducing kidney damage common with traditional tacrolimus use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the extended-release tacrolimus because it offers a potentially more convenient dosing schedule compared to the standard intermediate-release tacrolimus, which requires twice-daily administration. This new formulation simplifies the regimen by allowing for once-daily dosing while aiming to maintain the same therapeutic levels in the body. This could improve patient adherence and overall outcomes after lung transplantation by reducing the burden of medication management. The extended-release tablet promises to streamline treatment without compromising effectiveness, making it an attractive option for both patients and healthcare providers.

What evidence suggests that extended-release tacrolimus might be an effective treatment for lung transplant complications?

Research has shown that extended-release tacrolimus, such as Envarsus XR, helps prevent organ rejection after lung transplants. In this trial, some participants will receive extended-release tacrolimus to maintain stable drug levels in the bloodstream, potentially enhancing its effectiveness. Studies have found that tacrolimus generally stops the body from attacking the new lung, but its effectiveness can be affected by unpredictable changes in drug levels. Other participants will receive intermediate-release tacrolimus, the current standard of care. Early reports suggest that switching to extended-release tacrolimus can be safe and manageable for patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Anil Trindade, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have had a lung transplant, can consent to the study, and are treated at VUMC with good adherence to medical therapies. It's not for those with certain infections (Hepatitis B/C, HIV), high liver enzymes, unresolved kidney injury post-transplant, issues taking oral meds, pregnant or breastfeeding women, severe graft dysfunction post-transplantation, GI absorption problems, prior organ transplants or tacrolimus intolerance.

Inclusion Criteria

I have had a lung transplant.

Participant is able to give informed consent for participation in the study.

Actively receives care at VUMC and is adherent with medical therapies.

Exclusion Criteria

I have a history of seizures.

You are currently enrolled in another study where you are receiving a treatment.

I often have headaches.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IR-tacrolimus or LCP-tacrolimus for immunosuppression post-lung transplant

7 months

Regular visits for monitoring trough levels and side effects

Follow-up

Participants are monitored for safety, tolerability, and effectiveness of the treatment

2 months

Visits for eGFR assessment and quality of life evaluations

Extension

Optional continuation of monitoring for long-term outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Azathioprine
• Mycophenolate Mofetil Hydrochloride
• Prednisone
• Tacrolimus
• Tacrolimus Extended Release Oral Tablet [Envarsus]

Trial Overview The study tests if early use of Long-acting Tacrolimus (LCP-tacrolimus) after lung transplantation is safe and tolerable compared to immediate-release tacrolimus. The goal is to see if LCP-tacrolimus better preserves kidney function while still preventing rejection of the new lungs.

How Is the Trial Designed?

Group I: Immunosuppression with Extended-Release Tacrolimus Experimental Treatment 4 Interventions

LCP-tacrolimus administered daily to target a goal trough level of 10-14 ng/mL x 7 months (with Mycophenolate mofetil and prednisone). Additional standard immunosuppression with either mycophenolate mofetil (500-1500mg twice daily) OR Azathioprine (up to 2mg/kg daily) AND Prednisone (5-10mg daily) will be administered.

Group II: Immunosuppression with Intermediate Release Tacrolimus Active Control 4 Interventions

IR-tacrolimus administered twice daily to target a goal trough level of 10-14 ng/mL x 7 months (with Mycophenolate mofetil and prednisone). This is currently the standard of care at Vanderbilt University Medical Center and most other lung transplant centers (ISHLT Registry 2019). Additional standard immunosuppression with either mycophenolate mofetil (500-1500mg twice daily) OR Azathioprine (up to 2mg/kg daily) AND Prednisone (5-10mg daily) will be administered.

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

Approved in European Union as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of autoimmune diseases such as rheumatoid arthritis

Approved in United States as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Approved in Canada as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Veloxis Pharmaceuticals

Industry Sponsor

Trials

43

Recruited

3,200+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40294109/

Comparison of Early Conversion to LCP-Tacrolimus ... Tacrolimus is highly effective at preventing allograft rejection and prolonging survival after lung transplantation. However, erratic pharmacokinetics may limit ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04420195?term=tacrolimus&rank=2

NCT04420195 | Envarsus XR in Lung Transplant Envarsus XR is an FDA-approved drug for the prophylaxis of organ rejection in de novo kidney transplant patients or in kidney transplant patients converted ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11935420/

Erratic tacrolimus levels at 6 to 12 months post-lung ... Erratic tacrolimus levels at 6 to 12 months post-lung transplant were associated with poor lung transplant outcomes.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/ctr.70159

Comparison of Early Conversion to LCP‐Tacrolimus ... Tacrolimus is highly effective at preventing allograft rejection and prolonging survival after lung transplantation.

5. jhltonline.org jhltonline.org/article/S1053-2498(24)00114-1/fulltext

Randomized Controlled Trial Comparing Immediate versus ... Different studies have shown similar efficacy profiles for both tacrolimus formulas. LTx patients have higher tacrolimus serum trough levels compared to other ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4801790/

Overview of extended release tacrolimus in solid organ ... Overall, extended release tacrolimus was shown to be safe and effective for nonsensitized kidney transplant recipients[27]. Yang et al[28] performed a 24-wk ...

7. envarsusxr.com envarsusxr.com/hcp/efficacy-safety

Clinical Data | ENVARSUS XR® (tacrolimus extended- ... ENVARSUS XR offers lasting efficacy · At 1 year, recipients on ENVARSUS XR had a 9% lower risk of treatment failure vs those on Prograf® · At 2 years, recipients ...

8. jhltonline.org jhltonline.org/article/S1053-2498(20)30119-4/abstract

Efficacy and Safety of LCP-Tacrolimus (Envarsus XR® ... LCPT offers improved bioavailability and lower peak blood concentrations which may lead to fewer neurological adverse effects while allowing for adequate ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34974456/

Lung Transplant Outcomes in Adults in the United States The cumulative incidence of graft failure or death at 1 y posttransplant in adult lung transplant patients receiving TAC + MMF was 8.6% (95% ...