Hepatitis C Kidneys Transplantation for Kidney Failure

(THINKER-NEXT Trial)

Not currently recruiting at 11 trial locations

Overseen By Peter Reese, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: Amiodarone, Dronedarone

Disqualifiers: Hepatocellular carcinoma, Hepatitis B, HIV, 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: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether kidneys from donors with hepatitis C (HCV) can be safely transplanted into patients without the virus, using Epclusa (an antiviral medication) to clear any potential infection. The study aims to assess the function of these transplanted kidneys after one year and compare health outcomes, such as survival rates and infection risks, between recipients of HCV-infected kidneys and those who did not receive them. It suits individuals on the kidney transplant waiting list who lack a living donor and are not currently infected with hepatitis C. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using amiodarone or dronedarone.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using amiodarone or dronedarone.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Epclusa, a combination of sofosbuvir and velpatasvir, is safe and effective for kidney transplant patients. Studies have found this treatment works well for patients receiving kidneys from donors with hepatitis C (HCV).

One study discovered that using Epclusa before and after kidney transplants is safe for patients without HCV who receive a kidney from an HCV-positive donor. Another study with long-term follow-up confirmed that medications like Epclusa are effective and safe for kidney transplant recipients.

These findings suggest that Epclusa is a reliable option for managing HCV after receiving a kidney from an HCV-positive donor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for kidney failure, which often involves dialysis or transplantation with kidneys from donors without Hepatitis C, Epclusa offers a unique approach by enabling the use of Hepatitis C-infected kidneys for transplantation. Epclusa, a combination of sofosbuvir and velpatasvir, is effective at treating Hepatitis C, allowing these kidneys to be safely used without long-term viral complications. This expands the donor pool significantly and reduces waiting times for kidney transplants, providing hope for patients with kidney failure. Researchers are particularly excited because it leverages a novel strategy to address organ shortages, potentially revolutionizing kidney transplantation practices.

What evidence suggests that this treatment might be an effective treatment for kidney failure?

Research shows that the combination of sofosbuvir and velpatasvir, found in the medication Epclusa, effectively treats hepatitis C. In this trial, participants will receive Epclusa, which studies have shown to work well for kidney transplant patients, even those with chronic kidney disease. Specifically, sofosbuvir/velpatasvir has been safe and effective for recipients of kidneys from donors with hepatitis C. This means that patients who receive a kidney infected with hepatitis C and then take Epclusa have a good chance of eliminating the virus. Long-term follow-up data supports that medications like Epclusa are effective and safe for kidney transplant recipients. ^{1 2 3 5 6}

Who Is on the Research Team?

Peter Reese, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults on the kidney transplant waiting list without hepatitis C can join this trial. They must be over 18, have no living kidney donor, and a low to moderate immune response to potential donors (PRA ≤97%). Pregnant women, those planning pregnancy or breastfeeding, patients with certain heart medications or other liver diseases are excluded.

Inclusion Criteria

Your panel reactive antibody level should be 97% or below, but if it's 98-100%, you may still be included depending on specific antibody levels and other criteria.

I am on the active waiting list for a kidney transplant.

You cannot have donated a kidney while still alive.

Exclusion Criteria

Participation in another interventional study, from a period starting 6 months prior to screening to last study visit, that the study PIs judge would interfere with either the aims or the safety of the THINKER-NEXT study.

I have a chronic liver condition, but it's not NAFLD with normal enzymes.

You have tested positive for HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants receive a kidney transplant from a deceased donor infected with HCV

1 day

1 visit (in-person)

Treatment

Participants receive Epclusa (sofosbuvir/velpatasvir) for 12 weeks to treat HCV

12 weeks

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety, effectiveness, and allograft function post-treatment

12 weeks

Follow-up visits to assess SVR and kidney function

What Are the Treatments Tested in This Trial?

Interventions

• Epclusa

Trial Overview The study tests if kidneys from deceased donors with Hepatitis C can be safely transplanted into patients without Hepatitis C. After transplantation, recipients will receive Epclusa to treat the virus. Their health outcomes will be compared with those who received non-HCV infected kidneys and those on the waitlist.

How Is the Trial Designed?

Group I: Epclusa (sofosbuvir/velpatasvir) Experimental Treatment 1 Intervention

Epclusa is taken by mouth for 12 weeks as per the FDA label.

Epclusa is already approved in European Union, United States for the following indications:

Approved in European Union as Epclusa for:

• Chronic hepatitis C

Approved in United States as Epclusa for:

• Chronic hepatitis C

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a study of 249 patients with genotype 1b chronic hepatitis C, the combination therapy of daclatasvir and asunaprevir showed high efficacy, with sustained virological response rates of 86.3% overall, and similar rates in patients with chronic kidney disease (CKD) compared to those without.

The safety profile was comparable between patients with CKD and those without, with adverse event rates of 21.8% and 13.9% respectively, indicating that the treatment is safe for patients with non-dialysis CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease. Kondo, C., Atsukawa, M., Tsubota, A., et al.[2020]

In a study of 71 chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection, full-dose generic sofosbuvir combined with ribavirin, ledipasvir, or daclatasvir achieved a 100% sustained virological response (SVR) at 12 weeks after treatment cessation.

The study demonstrates that sofosbuvir-based DAA therapy is highly effective and safe for HCV-infected patients with advanced CKD, including those on dialysis, indicating its potential as a treatment option in low-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generic sofosbuvir-based direct-acting antivirals in hepatitis C virus-infected patients with chronic kidney disease. Manoj Kumar, ., Nayak, SL., Gupta, E., et al.[2022]

In a study of six male patients with end-stage renal disease on hemodialysis, the combination of reduced-dose sofosbuvir (SOF) and full-dose daclatasvir (DCV) was found to be a safe and effective treatment for chronic hepatitis C virus (HCV) genotype 3, with all patients achieving a sustained virological response after 12 weeks.

The treatment was well tolerated, with no serious adverse events reported, indicating that this regimen could be a viable option for hemodialyzed patients with HCV, including those with advanced liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis. Sperl, J., Frankova, S., Kreidlova, M., et al.[2022]

Sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) demonstrated high effectiveness in treating chronic hepatitis C in patients with severe renal impairment, achieving a sustained virological response (SVR12) rate of 94.8% in evaluable patients and 100% in per-protocol analyses.

The treatment was well-tolerated, with serious adverse events not linked to SOF/VEL or RBV, and common side effects like fatigue and headache were mostly mild, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment. Liu, CH., Chen, CY., Su, WW., et al.[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]

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]

The sofosbuvir-velpatasvir regimen achieved a high sustained virological response (SVR12) rate of 94.2% in 1277 patients with chronic hepatitis C virus (HCV) infection, indicating its strong efficacy.

Adding ribavirin did not significantly improve SVR12 rates for HCV genotypes 1 and 2, but it did enhance the response for genotype 3 patients, suggesting that ribavirin may be beneficial for specific HCV genotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis. Ren, XD., Fu, X., He, YQ., et al.[2022]

Citations

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

Epclusa® Use in Post-Kidney Transplant Patients A retrospective, single-center study was conducted in 40 kidney transplant recipients with HCV+ serology to assess the impact of HCV infection ...

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

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

3. cureus.com cureus.com/articles/253314-efficacy-of-sofosbuvir-and-velpatasvir-combination-in-the-treatment-of-hepatitis-c-virus-hcv-in-chronic-kidney-disease-ckd-patients

Efficacy of Sofosbuvir and Velpatasvir Combination in the ... In this descriptive study analyzing the effectiveness of sofosbuvir and velpatasvir combination for the treatment of HCV in CKD patients, we ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03809533

NCT03809533 | The Use of Hepatitis C Positive Kidneys in ... 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 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468024922015959

POS-078 LONG TERM OUTCOMES OF TREATMENT ... Over a long term follow up period, treatment of HCV with the newer directly acting antivirals is effective and safe in kidney transplant recipients.

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

Kidney Transplant Patients SVR12 was 95% for the sofosbuvir/velpatasvir treatment arm, which was superior to the SVR12 80% among patients receiving sofosbuvir plus ribavirin for 24 weeks ...