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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug sofosbuvir/velpatasvir for heart transplant patients?

Sofosbuvir/velpatasvir has shown high cure rates and is well-tolerated in patients with chronic hepatitis C, including those with complex conditions like cirrhosis or HIV co-infection. Additionally, sofosbuvir combined with other drugs has been effective and safe in heart transplant recipients with hepatitis C. ^{1 2 3 4 5}

How does the drug Sofosbuvir/Velpatasvir differ from other treatments for heart transplant patients?

Sofosbuvir/Velpatasvir is unique because it is a direct-acting antiviral combination originally used for treating hepatitis C, and it is being explored for heart transplant patients. This drug is known for its effectiveness and safety in treating hepatitis C without the need for interferon, which can have significant side effects. ^{1 4 6 7 8}

What is the purpose of this trial?

This is an open-label, pilot trial to test the safety and efficacy of transplantation of hearts from HCV seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the heart transplant waitlist. Treatment and prophylaxis will be administered, using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

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

2. 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]

3. Poland pubmed.ncbi.nlm.nih.gov

Sofosbuvir/velpatasvir in treatment-experienced HCV-infected patients - short report. [2022]

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

Sofosbuvir-based Interferon-Free Direct Acting Antiviral Regimens for Heart Transplant Recipients With Chronic Hepatitis C Virus Infection. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. Mexico pubmed.ncbi.nlm.nih.gov

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. [2021]

7. Mexico pubmed.ncbi.nlm.nih.gov

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Sofosbuvir plus velpatasvir combination for the treatment of chronic hepatitis C in patients with end stage renal disease on renal replacement therapy: A systematic review and meta-analysis. [2022]