HCV Positive Lung Transplant with Antiviral Therapy for Hepatitis C

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University Health Network, Toronto

Disqualifiers: Other trials

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to make lung transplants safer for patients without hepatitis C (HCV) by using lungs from HCV-positive donors. Researchers will treat the donor lungs with a technique called Normothermic Ex Vivo Lung Perfusion (EVLP) to reduce the risk of virus transmission. If an HCV infection occurs, patients will receive standard antiviral treatment with sofosbuvir-velpatasvir. This trial suits individuals currently waiting for a lung transplant who do not have hepatitis C. After the transplant, participants will be closely monitored for infections or other complications. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to benefit from this innovative approach.

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

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

What prior data suggests that Ex Vivo Lung Perfusion (EVLP) is safe for lung transplant recipients?

Research has shown that sofosbuvir-velpatasvir, also known as Epclusa, is generally safe for transplant patients. In past studies, almost all heart transplant patients who took this medication had their new heart functioning well after a year, with no major safety issues identified.

Additionally, lung transplant data indicates that the risk of rejection remains similar whether the lung comes from a donor with hepatitis C or not, suggesting that the treatment does not increase the risk of rejection.

Overall, the evidence supports that sofosbuvir-velpatasvir is safe and effective for patients receiving organ transplants from donors with hepatitis C. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatment of using sofosbuvir-velpatasvir for lung transplants from HCV-positive donors because it leverages a unique approach. Unlike traditional antiviral treatments, which typically aim to manage hepatitis C post-transmission, this method uses Normothermic Ex Vivo Lung Perfusion (EVLP) to reduce the viral load in donor lungs before transplantation. This pre-treatment minimizes the risk of hepatitis C transmission to recipients. Additionally, if recipients do become viremic, the direct-acting antiviral combination of sofosbuvir and velpatasvir is administered for 12 weeks, offering a targeted and effective way to clear the virus.

What evidence suggests that Ex Vivo Lung Perfusion (EVLP) and sofosbuvir-velpatasvir could be effective for reducing HCV transmission in lung transplants?

Studies have shown that the medication sofosbuvir-velpatasvir effectively treats hepatitis C virus (HCV) infections. Research indicates that this medication can eliminate the virus in most people after 12 weeks of treatment. In this trial, Normothermic Ex Vivo Lung Perfusion (EVLP) will treat HCV-positive donor lungs to reduce viral load and minimize the risk of HCV transmission. Patients who become viremic, defined as having at least two consecutive positive samples, will receive sofosbuvir-velpatasvir. Previous research demonstrated that lung transplant patients who received organs from HCV-positive donors and were treated with sofosbuvir-velpatasvir successfully eliminated the infection. Additionally, this treatment is generally well-tolerated and can greatly reduce the risk of complications from HCV after a transplant. ^{1 2 4 6 7}

Who Is on the Research Team?

Marcelo Cypel, MD MSc FRCSC

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for HCV negative patients on the lung transplant waitlist who can consent to receiving HCV positive lungs. They will be monitored closely and treated with antivirals if they get infected.

Inclusion Criteria

You do not have the hepatitis C virus as confirmed by a specific test.

Ability to provide written informed consent

I am on the list for a lung transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Monitoring

HCV negative recipients receive lungs from HCV positive donors, followed by initial monitoring for HCV infection

6 months

Regular visits for HCV PCR tests

Treatment

Participants who become viremic receive sofosbuvir/velpatasvir for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including long-term monitoring for HCV infection and complications

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ex Vivo Lung Perfusion (EVLP)
• Sofosbuvir-velpatasvir

Trial Overview The study tests whether treating donated HCV positive lungs with EVLP before transplant reduces infection rates in recipients. If patients do get infected, standard antiviral drugs are used as treatment.

How Is the Trial Designed?

Group I: HCV+ lung transplant to HCV- recipients Experimental Treatment 2 Interventions

HCV+ donor lungs will be treated with Normothermic Ex Vivo Lung Perfusion (EVLP) in order to reduce viral load and minimize risk of HCV transmission. Patients who become viremic defined as at least two consecutive positive samples will receive sofosbuvir/velpatasvir 400 mg/100 mg (Epclusa) for 12 weeks.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a phase 3 study of 111 patients with chronic hepatitis C, 97% achieved a sustained virologic response (SVR12) after 12 weeks of treatment with sofosbuvir-velpatasvir, demonstrating its high efficacy across various HCV genotypes.

The treatment was well tolerated, with a safety profile similar to placebo, and only one patient discontinued due to an adverse event not related to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection. Asselah, T., Shafran, SD., Bourgeois, S., et al.[2020]

In a study of 19 kidney transplant recipients treated with sofosbuvir-daclatasvir, 100% achieved a sustained virological response 12 weeks after treatment, indicating the treatment's high efficacy against chronic hepatitis C virus (HCV) infection.

Patients also showed significant improvements in liver function, with notable decreases in liver enzyme levels (ALT and AST), and stable kidney function throughout the therapy, suggesting that the treatment is well-tolerated and safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis C viral infection with sofosbuvir and daclatasvir in kidney transplant recipients. Huang, H., Tang, H., Deng, H., et al.[2021]

Sofosbuvir/velpatasvir/voxilaprevir is highly effective for treating hepatitis C virus (HCV) in patients with genotypes 1 through 6 who have previously been treated with an NS5A inhibitor, as shown in the POLARIS-1 study with a 12-week treatment duration.

The treatment is generally safe, with common side effects including headache, fatigue, diarrhea, and nausea, making it a viable option for patients with chronic HCV, especially those with prior exposure to direct-acting antivirals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C. Chahine, EB., Kelley, D., Childs-Kean, LM.[2021]

In a study of 26 HCV-negative kidney transplant recipients from HCV-infected donors, treatment with Sofosbuvir/Velpatasvir for 12 weeks was effective, with all patients maintaining negative HCV RNA levels post-treatment.

The treatment was deemed safe, as adverse events occurred in 57.7% of patients, but none were related to the medication, and renal function remained stable throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir Prophylaxis for 12 Weeks in Hepatitis C Virus (HCV)-Negative Recipients Receiving Kidney Transplantation from HCV-Positive Donors. Chen, R., Li, D., Zhang, M., et al.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2950133423000290

Outcomes of lung transplantation from donors with hepatitis ... Another analysis of United Network of Organ Sharing data reported that overall rates of acute rejection were similar in lung transplant recipients who received ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10306429/

The SHELTER Trial of Transplanting Hepatitis C Virus– ... SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1812406

Heart and Lung Transplants from HCV-Infected Donors to ... We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03207399?term=Epclusa&rank=1

Lung Transplantation in Chronic HCV Infection With Post ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10328796/

Preemptive antiviral therapy in lung transplantation from ... The study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors ...

6. askgileadmedical.com askgileadmedical.com/docs/epclusa/epclusa-use-post-heart-transplant

Epclusa® Use Post-Heart Transplant Nearly all participants (94%; 15/16) with ≥12 months of follow-up had graft survival, and. 1 recipient of a heart transplant died at post-transplant Month 8 ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150105/

A single center experience of concomitant administration ... The aim of this study was to report our experience with the concomitant administration of SOF/VEL and amiodarone in heart and lung transplant recipients.