Sofosbuvir/Velpatasvir for Kidney Transplant Recipients

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amit D Tevar, 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 a treatment for kidney transplant patients receiving kidneys from donors with hepatitis C (HCV). The goal is to evaluate how effectively the combination of sofosbuvir and velpatasvir prevents or treats HCV in these patients. Two groups participate: one receives treatment if the virus is detected post-transplant, while the other begins treatment immediately. The trial seeks individuals with end-stage kidney disease who are on dialysis and awaiting a kidney transplant, but who do not have hepatitis C themselves. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information 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.

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

Research has shown that the drug combination sofosbuvir/velpatasvir is generally safe for individuals who have undergone a kidney transplant. One study found that this treatment was effective and safe for patients who received kidneys from donors with hepatitis C. Most patients tolerated the treatment well, experiencing only mild side effects. The FDA has also approved this drug combination for treating hepatitis C in other cases, indicating that its safety has been thoroughly studied. Overall, evidence suggests that sofosbuvir/velpatasvir is well-tolerated in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sofosbuvir/velpatasvir for kidney transplant recipients because this combination targets hepatitis C virus (HCV) with a unique one-two punch. While most treatments for HCV involve various drug combinations to target multiple stages of the virus's life cycle, sofosbuvir/velpatasvir combines a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir) with a NS5A inhibitor (velpatasvir) to effectively halt viral replication. This dual-action approach is particularly promising for kidney transplant recipients who receive organs from HCV-positive donors, as it provides a streamlined, 12-week oral treatment that could make post-transplant care simpler and potentially more effective than current multi-drug regimens.

What evidence suggests that sofosbuvir/velpatasvir might be an effective treatment for kidney transplant recipients?

Research has shown that the medication sofosbuvir/velpatasvir is effective and safe for treating hepatitis C in individuals who have undergone a kidney transplant. In this trial, participants will receive sofosbuvir/velpatasvir in different treatment arms. One arm treats kidney recipients from HCV seropositive viremic donors starting on post-operative day 1. Another arm monitors recipients from HCV seropositive non-viremic donors and initiates treatment if HCV RNA is detected. Studies have found that using this treatment before and after a transplant successfully controls hepatitis C. Specifically, if the hepatitis C virus is detected, taking sofosbuvir/velpatasvir for 12 weeks can effectively eliminate the virus. This medication stops the virus from multiplying, preventing its spread. It has proven effective in transplant patients, making it a suitable option for those receiving kidneys from donors with hepatitis C. ^{1 4 5 6 7}

Who Is on the Research Team?

Fernanda Silviera, MD

Principal Investigator

University of Pittsburgh

Amit Tevar, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults over 18 with end-stage renal disease on the kidney transplant waitlist at UPMC, without a living donor, and willing to use contraception post-transplant. Excluded are pregnant women, those with liver cirrhosis or certain heart conditions, HIV/HBV positive individuals, previous organ transplants recipients, or anyone with contraindications as assessed by investigators.

Inclusion Criteria

I am on dialysis or have stage 5 kidney disease.

I am on the kidney transplant list at UPMC with end-stage renal disease.

You don't have a living donor who can donate a kidney.

Exclusion Criteria

You are pregnant.

I am currently receiving treatment for hepatitis C.

You are on a waiting list for receiving multiple organs for transplantation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Treatment

Kidney transplantation from HCV seropositive donors to HCV seronegative recipients. Immediate post-operative treatment with sofosbuvir/velpatasvir for 12 weeks in arm 2.

12 weeks

Regular monitoring visits

Monitoring and Transmission-Triggered Treatment

Monitoring for HCV RNA in recipients from HCVAb+/NAT- donors. Initiation of 12-week sofosbuvir/velpatasvir treatment if HCV RNA is detected.

Up to 1 year

Close monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of virological response.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• sofosbuvir/velpatasvir

Trial Overview The trial tests if kidneys from hepatitis C positive donors can be safely transplanted into hepatitis C negative patients using sofosbuvir/velpatasvir for prevention and treatment of potential HCV transmission. It's an open-label study comparing two approaches based on the donor's viral status.

How Is the Trial Designed?

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

Starting post-operative day 1, kidney 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

Kidney 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?

Amit D Tevar, MD

Lead Sponsor

Trials

1

Recruited

30+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Published Research Related to This Trial

In a systematic review of 233 randomized controlled trials on kidney transplant immunosuppression, only 69% reported adverse events (AEs), and many did not adequately define or measure the severity of these events, raising concerns about the reliability of the data for clinical decision-making.

Trials that reported AEs were more likely to be industry-funded, multicenter, and have shorter follow-up periods, suggesting potential biases in the reporting of adverse effects that could impact patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness of reporting of adverse events in trials of maintenance immunosuppression in kidney transplantation: a systematic review. Howell, M., Yeo, R., Tong, A., et al.[2022]

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]

In a study of 4,110 kidney transplant recipients, 38.9% of those hospitalized experienced adverse safety events, highlighting the significant risk of complications in this population.

Factors such as lower estimated glomerular filtration rate (GFR), history of cardiovascular disease, and diabetes were associated with a higher incidence of these safety events, indicating the need for careful monitoring and management of medications in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety events in kidney transplant recipients: results from the folic Acid for vascular outcome reduction in transplant trial. Weir, MR., Gravens-Muller, L., Costa, N., et al.[2018]

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]

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]

In a study of 6 male kidney transplant patients with hepatitis C, treatment with sofosbuvir and daclatasvir resulted in a 100% sustained virological response rate after 12 weeks, indicating high efficacy in clearing the virus.

The treatment was generally safe, with no serious adverse events reported, although two patients required a reduced dose of sofosbuvir due to elevated serum creatinine levels, suggesting careful monitoring of kidney function is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sofosbuvir and daclatasvir in treatment of kidney transplantation recipients with hepatitis C virus infection. Xue, Y., Zhang, LX., Wang, L., et al.[2021]

Citations

1. 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- ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03809533

NCT03809533 | The Use of Hepatitis C Positive Kidneys in ... If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10175878/

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis ... Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. ...

4. ajkd.org ajkd.org/article/S0272-6386(23)00592-9/fulltext

A Systematic Review for the KDIGO 2022 Hepatitis C ... Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies ...

5. 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 ...

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

Epclusa® Use in Post-Kidney Transplant Patients Efficacy and Safety of Sofosbuvir and Velpatasvir in Renal. Transplant Recipients with Chronic Hepatitis C Virus Infection [Abstract SP786].

7. hcvguidelines.org hcvguidelines.org/guidance/kidney-transplant-patients/

Kidney Transplant Patients One study evaluated treatment safety and efficacy among 20 HCV-infected kidney transplant recipients (88% genotype 1; 50% with advanced fibrosis; 60% treatment- ...