UV Light + Antivirals for Lung Transplant Recipients from Hepatitis B Donors

(CLEAR-HBV Trial)

Overseen By Atul Humar, MD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University Health Network, Toronto

Must be taking: Hepatitis B vaccine

Must not be taking: Antivirals

Disqualifiers: Chronic liver disease, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate peri-operative period

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to safely use lungs from donors with Hepatitis B for transplants. The study combines a special UV light treatment (EVLP UV Light Treatment) with antiviral medications to determine if this method prevents the spread of Hepatitis B to lung transplant recipients. Candidates eligible for a lung transplant, who have tested negative for Hepatitis B and have been vaccinated against it, might be suitable for this trial. The goal is to increase the availability of donor lungs without compromising safety. As a Phase 4 trial, this research aims to understand how the already FDA-approved treatment benefits more patients, contributing to broader medical knowledge.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for the treatments in this trial?

Research shows that using UV light on lungs outside the body safely prepares them for transplant. Studies have found that UV light can significantly reduce viruses, like hepatitis C, in donor lungs, helping to prevent viral spread during the transplant.

Animal tests have proven this method safe. It treats higher-risk donor lungs, improving their suitability for transplant. The antiviral drugs used are approved treatments and are generally well-tolerated. No major safety issues have been reported in humans for these treatments in similar situations.

For those considering joining a trial, this information indicates that the treatment has undergone thorough testing and is considered safe based on previous research. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this treatment because it combines UV light therapy with antiviral medications, offering a unique approach to making lung transplants from Hepatitis B donors safer. Unlike the standard of care, which typically focuses on antiviral drugs alone, this treatment uses UV light during ex-vivo lung perfusion to potentially reduce the viral load before transplantation. Additionally, the use of a short course of Entecavir and HBIG right after surgery aims to protect the recipient from the virus more effectively. This innovative combination could lead to better outcomes for lung transplant recipients by minimizing the risk of Hepatitis B transmission.

What evidence suggests that UV Light + Antivirals is effective for lung transplant recipients from Hepatitis B donors?

In this trial, participants will receive lungs from HBV NAT+ donors, treated with EVLP UV light therapy during ex-vivo perfusion. Research has shown that using EVLP with UV light can effectively kill viruses like hepatitis C in donor lungs, making them safer for transplants. This method has lowered virus levels in test models. Participants will also receive Entecavir and HBIG prophylaxis in the immediate peri-operative period. Entecavir, an antiviral drug, helps prevent hepatitis B infection after transplants by controlling the virus. Studies have found that Entecavir and HBIG, a hepatitis B immune treatment, help maintain transplant patients' health by preventing the spread of hepatitis B. Together, these treatments offer a promising way to safely use lungs from donors with hepatitis B. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for lung transplant recipients. It's specifically looking at the safety of using lungs from donors with Hepatitis B when treated with a special procedure and antiviral medications.

Inclusion Criteria

I am listed for a lung transplant.

HBV NAT negative

Provides written informed consent

Exclusion Criteria

I have tested positive for HTLV 1/2.

My liver disease is at least stage 2 fibrosis.

HIV positive

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Lungs from HBV NAT+ donors are treated with UV light therapy during ex-vivo perfusion, and patients receive Entecavir and HBIG prophylaxis in the immediate peri-operative period

Immediate peri-operative period

In-person visits for transplantation and initial treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood samples taken at days 3 and 7, then weekly for the first 4 weeks, then every two weeks until 12 weeks post-transplant, and at month 6

6 months

Multiple visits for blood sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Entecavir
• EVLP UV Light Treatment
• HBIG

Trial Overview The study tests if it's safe to transplant lungs treated with EVLP (a technique that keeps the lungs working outside the body) and UV light, along with giving patients Entecavir and HBIG as antivirals against Hepatitis B.

How Is the Trial Designed?

Group I: UV Light + Short-course Entecavir/HBIG Experimental Treatment 3 Interventions

Patients will receive lungs from HBV NAT+ donors, which will be treated with UV light therapy during ex-vivo perfusion. Patients will also receive Entecavir and HBIG prophylaxis in the immediate peri-operative period.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213260019302681

Prevention of viral transmission during lung transplantation ... Early and intermediate clinical outcomes were not significantly different between patients receiving viraemic HCV donor lungs and HCV-negative donor lungs.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9098710/

Ex Vivo Lung Perfusion: A Review of Current and Future ... Ex vivo lung perfusion (EVLP) is a modality that allows donor lungs to be evaluated in a closed circuit outside of the body and extends lung donor assessment.

3. nature.com nature.com/articles/s41467-018-08261-z

Inactivating hepatitis C virus in donor lungs using light ... Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor ...

4. researchgate.net researchgate.net/figure/Effect-of-EVLP-and-light-based-therapies-LbT-on-HCV-RNA-levels-in-HCV-NAT-human-donor_fig2_330711787

Effect of EVLP and light-based therapies (LbT) on HCV ... EVLP systems have also proven to be effective in treating donor lungs infected with chronic hepatitis C. In an early preclinical model, lung resident hepatitis ...

5. journal.chestnet.org journal.chestnet.org/article/S0012-3692(18)32283-9/fulltext

The Future of Lung Transplantation - Chest Journal Treatment with antibacterial therapy could ameliorate donor-derived bacterial infections, and a recent study using ultraviolet light therapy of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07189377

Combined Light, ExVivo, and Antivirals for Recipients of ... The aim of the study is to show that transplantation of organs from HBV NAT+ve donors is safe with the use of UV light treatment on EVLP ...

7. eujtransplantation.com eujtransplantation.com/article/view/57

THE PRESENT AND FUTURE OF EX-VIVO LUNG ... During EVLP, high risk donor lungs can be assessed, treated and repaired prior to transplantation. Indeed, many transplant centers have now ...