Hepatitis C Positive Liver Transplants for Liver Transplant Recipients

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fernanda P Silveira, MD, MS

Must not be taking: Amiodarone, Sofosbuvir/Velpatasvir

Disqualifiers: HIV, Hepatitis B, Drug use, 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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of transplanting livers from Hepatitis C-positive donors into patients awaiting a liver transplant. It examines two types of donor livers: those with inactive Hepatitis C and those with active Hepatitis C. After the transplant, patients receive sofosbuvir/velpatasvir, an antiviral medication, to manage or prevent Hepatitis C infection. This trial targets patients on the liver transplant list without a living donor who can regularly visit UPMC for follow-up care. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the treatment used in this study, sofosbuvir/velpatasvir, is generally safe for liver transplant patients. Studies have found that most people tolerate this medication well, experiencing no severe side effects. It has been successfully used in patients who have undergone liver transplants. This drug combination effectively combats the hepatitis C virus, crucial for those receiving livers from donors exposed to the virus.

In earlier studies, patients who took sofosbuvir/velpatasvir after liver transplants reported few side effects, suggesting that the treatment should be safe for participants in this trial as well. Additionally, the FDA has approved this medication for treating hepatitis C, which supports its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sofosbuvir/velpatasvir because it offers a comprehensive approach to treating hepatitis C in liver transplant recipients. Unlike traditional treatments, which often involve separate drugs with different mechanisms, sofosbuvir/velpatasvir combines a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir) and a NS5A inhibitor (velpatasvir) into a single oral medication. This fixed-dose combination can simplify treatment regimens and improve patient compliance. Additionally, it targets the virus with a dual mechanism, potentially increasing effectiveness and reducing the chance of resistance compared to using one type of inhibitor alone.

What evidence suggests that this trial's treatments could be effective for liver transplant recipients?

Research has shown that the combination of sofosbuvir and velpatasvir effectively treats Hepatitis C. In earlier studies, 94% of patients cleared the virus after 12 weeks of treatment. This treatment stops the virus from reproducing, helping to control the infection. In this trial, participants receiving livers from HCV seropositive viremic donors will start a 12-week course of sofosbuvir/velpatasvir on post-operative day 1. Those receiving livers from HCV seropositive non-viremic donors will be monitored for HCV, with treatment beginning if HCV RNA is detected. These findings suggest that the treatment can be highly effective for transplant patients receiving livers from donors with Hepatitis C. ^{1 2 4 6 7}

Who Is on the Research Team?

Fernanda Silviera, MD

Principal Investigator

University of Pittsburgh

Naudia Jonassaint, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults over 18 on the UPMC liver transplant waitlist, without HIV or hepatitis B, and no history of multi-organ transplants or certain drug uses. They must be willing to travel for post-transplant care and use contraception for a year.

Inclusion Criteria

Have panel reactive antibody level of <98%

Able to provide informed consent

Listed for an isolated liver transplant at UPMC

Exclusion Criteria

I am currently receiving treatment for hepatitis C.

HCVAb or HCV RNA positive

You are on the waiting list for a transplant involving multiple organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Immediate Post-operative Treatment

Liver transplantation from HCV seropositive donors to HCV seronegative recipients, followed by immediate post-operative treatment with sofosbuvir/velpatasvir for 12 weeks in the prophylaxis arm

12 weeks

Regular monitoring visits

Transmission-triggered Treatment

Monitoring for HCV transmission in recipients of HCVAb+/NAT- donor livers, with treatment initiated upon detection of HCV RNA

Up to 1 year

Regular monitoring visits

Follow-up

Participants are monitored for safety, effectiveness, and virological response after treatment

1 year

Regular follow-up visits

Long-term Follow-up

Monitoring for incidence of graft loss, allograft rejection, and other outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Sofosbuvir/Velpatasvir

Trial Overview The study tests if Hepatitis C positive livers can safely be transplanted into patients without Hepatitis C. It involves two approaches: one where treatment starts only if the virus is detected after transplant, and another with immediate preventive treatment.

How Is the Trial Designed?

Group I: HCV seropositive viremic (HCV Ab+/NAT+) donor Experimental Treatment 1 Intervention

Post-operative day 1, liver recipients will be treated with 12-week oral course of sofosbuvir/ velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

Group II: HCV seropositive non-viremic (HCV Ab+/NAT-) donor Experimental Treatment 1 Intervention

Liver recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated. Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

Who Is Running the Clinical Trial?

Fernanda P Silveira, MD, MS

Lead Sponsor

Trials

2

Recruited

400+

Naudia Jonassaint. MD

Lead Sponsor

Trials

1

Recruited

70+

Naudia Jonassaint

Lead Sponsor

Trials

1

Recruited

70+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5441022/

Hepatitis C Virus and Liver Transplantation - PMC The group that received sofosbuvir/velpatasvir plus ribavirin for 12 weeks achieved the highest SVR12 rate (94%) compared to the groups without ribavirin for 12 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7772723/

Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in ... This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients ...

3. hcvguidelines.org hcvguidelines.org/guidance/treatment-of-hcv-uninfected-transplant-recipients-receiving-organs-from-hcv-viremic-donors/

Treatment of HCV-Uninfected Transplant Recipients ... Of the 51 patients with complete treatment data, 64% were treated with glecaprevir/pibrentasvir and 36% received sofosbuvir/velpatasvir. All ...

4. frontiersin.org frontiersin.org/journals/gastroenterology/articles/10.3389/fgstr.2025.1511150/full

Real-world effectiveness of sofosbuvir/velpatasvir ... Conclusion: SOF+VEL ± RBV, GLE+PIB, and SOF+VEL+VOX had good antiviral effectiveness for chronic HCV-GT3 infection in real-world settings.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1600613523007967

Outcomes of early vs late treatment initiation in solid organ ... Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02728206

Sofosbuvir/Velpatasvir Fixed-Dose Combination in HCV ... The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination ...

7. askgileadmedical.com askgileadmedical.com/docs/epclusa/epclusa-use-post-liver-transplant/pdf

Epclusa® Use Post-Liver Transplantation Short-Duration Sofosbuvir/Velpatasvir Safe and. Effective in Treating HCV Infection Immediately After Liver Transplant [Poster 604]. Paper.