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

26 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Sofosbuvir-velpatasvir for treating HCV in lung transplant patients?

Research shows that Sofosbuvir-velpatasvir is highly effective in treating hepatitis C, with cure rates exceeding 90% in various conditions, including liver transplants and patients with liver cirrhosis. This suggests it could also be effective for HCV-positive lung transplant patients. ^{1 2 3 4 5}

Is Sofosbuvir/Velpatasvir safe for use in humans?

Sofosbuvir/Velpatasvir has been shown to be safe in various studies, including those involving kidney transplant recipients and patients with chronic hepatitis C. Common side effects include headache, fatigue, and nausea, but serious side effects were rare and not related to the medication. ^{2 6 7 8 9}

How is the drug Sofosbuvir-velpatasvir unique for treating HCV in lung transplant patients?

Sofosbuvir-velpatasvir is unique because it is a pangenotypic (effective against all types) direct-acting antiviral combination specifically designed to treat hepatitis C, making it suitable for HCV-positive lung transplant patients who need effective viral clearance before or after transplantation. ^{1 2 10 11 12}

What is the purpose of this trial?

In this study HCV negative recipients will be transplanted with HCV positive lungs. Investigators will attempt to decrease infectivity rates by performing Normothermic Ex vivo Lung Perfusion (EVLP), which is an approved method of donor lung preservation, assessment and treatment, and could be an excellent platform to reduce/eliminate hepatitis C virus. Patients will be treated by the standard approved direct-acting antivirals (DAAs) if infection occurs. It is planned to enroll 20 patients from the Lung transplant wait list in this study. Patients will be actively followed for 6 months including HCV PCR tests and then for up for 5 years to look for evidence of HCV infection and any liver or extra-hepatic complications, as well as standard post-transplant complications. This will be a single center pilot study.

Research Team

Marcelo Cypel, MD MSc FRCSC

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

References

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

Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report. [2020]

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

Sofosbuvir/Velpatasvir: The First Pangenotypic Direct-Acting Antiviral Combination for Hepatitis C. [2018]

3. Turkey pubmed.ncbi.nlm.nih.gov

Efficacy of Posttransplant Ledipasvir-Sofosbuvir in the Treatment of Patients Who Have Undergone Chronic Hepatitis C-Related Liver Transplant. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of 12-weeks velpatasvir plus sofosbuvir-based regimen in HCV-naive subjects with mild fibrosis: a meta-analysis. [2020]

6. United States 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. [2021]

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

Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C. [2021]

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

Sofosbuvir-velpatasvir single-tablet regimen administered for 12 weeks in a phase 3 study with minimal monitoring in India. [2020]

9. England 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. [2020]

10. Denmark pubmed.ncbi.nlm.nih.gov

Successful treatment of donor-derived hepatitis C infection in a lung transplant recipient. [2021]

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

Outcomes after lung transplantation and practices of lung transplant programs in the United States regarding hepatitis C seropositive recipients. [2011]

12. Denmark pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis C viral infection with sofosbuvir and daclatasvir in kidney transplant recipients. [2021]