Sofosbuvir/Velpatasvir for Heart Transplant

Overseen By Christopher Sciortino, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mary E. Keebler, MD

Must not be taking: Amiodarone

Disqualifiers: HIV, Hepatitis B, Liver cirrhosis, 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

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 using hearts from hepatitis C (HCV) positive donors for heart transplants. Participants will receive sofosbuvir/velpatasvir to prevent or treat hepatitis C infection after the transplant. The study consists of two parts: one for hearts from donors with signs of past HCV infection but no active virus, and another for donors with active HCV infection. Individuals with end-stage heart failure on the heart transplant list at UPMC who can attend follow-up visits for a year after the transplant might be suitable candidates. 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 does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using amiodarone for heart rhythm issues.

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

Research shows that the drug combination sofosbuvir/velpatasvir is generally safe for people who have had a heart transplant. In one study, almost all participants (94%) had their new heart functioning well a year after the transplant. Another study found that this drug combination was safe and effective for recipients of organs from donors with the hepatitis C virus (HCV).

These studies suggest that sofosbuvir/velpatasvir is usually well-tolerated. However, since researchers are still testing this treatment, side effects can occur. It's important to discuss any concerns with your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sofosbuvir/velpatasvir for heart transplant patients from HCV-positive donors because it offers a proactive approach to managing potential HCV infections. Unlike standard antiviral treatments that are typically reactive, this combination drug acts directly to inhibit the hepatitis C virus (HCV) replication through two mechanisms: sofosbuvir is a nucleotide analogue HCV NS5B polymerase inhibitor, and velpatasvir is a NS5A inhibitor. This dual-action strategy could potentially streamline the post-transplant process by addressing HCV transmission right from the start, which is particularly important for patients receiving hearts from viremic donors. This approach has the potential to not only prevent infection but also improve overall transplant success rates and patient outcomes.

What evidence suggests that this trial's treatments could be effective for heart transplant patients?

Research has shown that the drug combination sofosbuvir/velpatasvir effectively treats hepatitis C (HCV) in transplant recipients. In this trial, participants receiving hearts from HCV seropositive non-viremic donors will be monitored for HCV, and treatment with sofosbuvir/velpatasvir will begin if HCV RNA is detected. Participants receiving hearts from HCV seropositive viremic donors will start treatment with sofosbuvir/velpatasvir on post-operative day 1. Studies have found that heart transplant patients treated with these drugs have survival rates similar to those who received hearts from donors without HCV. When the heart donor had HCV, sofosbuvir/velpatasvir successfully eliminated the virus. For transplant patients, this treatment is part of successful plans to protect the new heart from the virus. These drugs stop the virus from multiplying, making them a reliable choice for managing HCV in heart transplant cases. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 on the UPMC heart transplant waitlist with end-stage heart failure and no major issues preventing a liver transplant. They must be able to visit UPMC post-transplant for at least a year, agree to use contraception for that period, and provide informed consent. Both HCV antibody-positive individuals, whether they currently have active hepatitis C or not (HCV NAT negative or positive), can join.

Inclusion Criteria

You have had a heart transplant procedure at UPMC.

You have a high level of antibodies in your blood that may prevent you from participating in the study.

I have no known reasons preventing me from having a liver transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Treatment

Heart transplantation from HCV seropositive donors to HCV seronegative recipients, followed by initiation of sofosbuvir/velpatasvir treatment

12 weeks

Frequent monitoring visits post-transplant

Follow-up

Participants are monitored for HCV transmission and adverse events, with virological response assessed at 4 weeks, end of treatment, and 12 weeks after completion of therapy

1 year

Regular follow-up visits for monitoring

Long-term Follow-up

Participants are monitored for adverse events and HCV status up to 5 years post-transplant

5 years

What Are the Treatments Tested in This Trial?

Interventions

• sofosbuvir/velpatasvir

Trial Overview The trial tests if it's safe and effective to transplant hearts from donors with different hepatitis C statuses into recipients without hepatitis C. It uses sofosbuvir/velpatasvir as treatment/prophylaxis after transplantation, depending on the donor's infection status.

How Is the Trial Designed?

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

HCV seropositive viremic (HCV Ab+/NAT+) donor hearts to HCV seronegative recipients. Starting post-operative day 1, heart 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). Intervention: Drug: sofosbuvir/velpatasvir

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

HCV seropositive non-viremic (HCV Ab+/NAT-) donor hearts to HCV seronegative recipients. Heart 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). Intervention: Drug: sofosbuvir/velpatasvir

Who Is Running the Clinical Trial?

Mary E. Keebler, MD

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

The combination of sofosbuvir and velpatasvir (Epclusa®) is a once-daily, single-tablet treatment that has shown very high rates of sustained virological response (SVR12) in adults with chronic hepatitis C virus (HCV) genotypes 1-6, including those with cirrhosis or HIV-1 co-infection, based on phase III ASTRAL trials.

Sofosbuvir/velpatasvir is generally well tolerated with low rates of adverse events, making it a safe and effective treatment option for a wide range of patients with chronic HCV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/Velpatasvir: A Review in Chronic Hepatitis C. Greig, SL.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9782687/

Review of heart transplantation from hepatitis C-positive ... With the effective treatment against HCV with DAAs, the 1-year survival rate is 90.4% in HCV-positive recipients similar to HCV-negative recipients[37,48,61].

2. sciencedirect.com sciencedirect.com/science/article/pii/S0914508725002357

Early outcomes in patients undergoing heart re- ... 2-year survival was similar in heart re-transplantation from hepatitis C virus (HCV) + and HCV– donors. •.

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. onlinejcf.com onlinejcf.com/article/S1071-9164(17)31124-7/fulltext

Rational Heart Transplant From a Hepatitis C Donor Cardiac donor–derived hepatitis C was cured with the use of a pangenotypic direct-acting antiviral agent, velpatasvir/sofosbuvir.

5. jhltopen.org jhltopen.org/article/S2950-1334(25)00074-6/fulltext

A single center experience of concomitant administration ... Results. Twenty thoracic transplant recipients (10 lung and 10 heart) from an HCV viremic donor received SOF/VEL in this open-label protocol.

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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8434773/

Sofosbuvir/Velpatasvir Prophylaxis for 12 Weeks in ... Sofosbuvir/Velpatasvir pre- and post-transplantation treatment was effective and safe in HCV-uninfected recipients who received a transplant kidney from HCV ...