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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, pilot trial to test the safety and efficacy of transplantation of kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney 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).

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.

What data supports the effectiveness of the drug sofosbuvir/velpatasvir for kidney transplant recipients?

Research shows that sofosbuvir/velpatasvir was effective and safe for kidney transplant recipients who received kidneys from donors with hepatitis C, as all patients had no detectable virus after treatment. ^{1 2 3 4 5}

Is Sofosbuvir/Velpatasvir safe for kidney transplant recipients?

The research articles provided do not contain specific safety data for Sofosbuvir/Velpatasvir in kidney transplant recipients. However, they highlight that kidney transplant patients are generally at increased risk for safety events due to reduced kidney function and multiple medications. ^{6 7 8 9 10}

How is the drug sofosbuvir/velpatasvir unique for kidney transplant recipients?

Sofosbuvir/velpatasvir is unique for kidney transplant recipients because it allows HCV-negative patients to safely receive kidneys from HCV-positive donors, effectively preventing HCV infection post-transplant. This drug is a once-daily, single-tablet regimen that targets multiple genotypes of the hepatitis C virus, making it versatile and effective in various patient populations. ^{1 4 11 12 13}

Research Team

Amit Tevar, MD

Principal Investigator

University of Pittsburgh

Fernanda Silviera, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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 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]

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 Prophylaxis for 12 Weeks in Hepatitis C Virus (HCV)-Negative Recipients Receiving Kidney Transplantation from HCV-Positive Donors. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

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

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

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

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

Efficacy and safety of sofosbuvir and daclatasvir in treatment of kidney transplantation recipients with hepatitis C virus infection. [2021]

5. Poland pubmed.ncbi.nlm.nih.gov

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

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

Development of a Predictive Model for Drug-Related Problems in Kidney Transplant Recipients. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Usability of mobile technology to screen for drug-drug interactions in kidney transplant patients. [2014]

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

Incidence of Statin-Associated Adverse Events in Kidney Transplant Recipients. [2023]

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

Safety events in kidney transplant recipients: results from the folic Acid for vascular outcome reduction in transplant trial. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Completeness of reporting of adverse events in trials of maintenance immunosuppression in kidney transplantation: a systematic review. [2022]

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

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

12. Turkey pubmed.ncbi.nlm.nih.gov

Virological Response to Sofosbuvir-Based Treatment in Renal Transplant Recipients With Hepatitis C in Pakistan. [2021]

13. 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]