Hepatitis C Kidneys Transplantation for Kidney Failure

(THINKER-NEXT Trial)

Recruiting at 11 trial locations

Overseen By Peter Reese, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

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

201 Participants Needed

Trial Summary

What is the purpose of this trial?

The Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients \[THINKER-NEXT\] study will include adult kidney transplant candidates without hepatitis C virus (HCV) infection on the transplant waiting list who will consent to kidney transplantation from a deceased donor infected with HCV, followed by treatment with a direct acting antiviral. The one-year allograft function and one-year risk of CMV infection will be compared between THINKER-NEXT kidney transplant recipients and matched recipients who received hepatitis C uninfected kidney transplants (these patients are called Transplant Cohort). The survival rate of patients opting-in for offers of kidneys from HCV-viremic donors will be compared to the survival rate of matched comparators from the kidney transplant waitlist who did not consent to receive offers of a HCV-viremic kidney. Lastly, renal pathologic findings will be compared among HCV-viremic donors and HCV-negative comparator donors.

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.

What data supports the idea that Hepatitis C Kidneys Transplantation for Kidney Failure (also known as: Epclusa, Epclusa, sofosbuvir/velpatasvir) is an effective treatment?

The available research shows that the drug sofosbuvir/velpatasvir is effective for kidney transplant patients who receive kidneys from donors with Hepatitis C. In a study, all patients who received this drug after their transplant had no detectable Hepatitis C virus in their blood after 12 weeks of treatment. This suggests that the drug is effective in preventing the spread of the virus from the donor kidney to the recipient. Additionally, the study found that the drug was safe, as none of the adverse events reported were related to the medication. This indicates that sofosbuvir/velpatasvir is both effective and safe for use in this context. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Epclusa (sofosbuvir/velpatasvir) for kidney transplantation in patients with kidney failure?

Research shows that sofosbuvir/velpatasvir is effective and safe for preventing hepatitis C in patients who received a kidney from an infected donor, with all patients having no detectable virus after treatment. ^{1 2 3 4 5}

What safety data exists for using Sofosbuvir/Velpatasvir in kidney transplants from HCV-positive donors?

A study evaluated the safety of Sofosbuvir/Velpatasvir in HCV-negative recipients receiving kidneys from HCV-positive donors. All 26 patients completed the 12-week treatment, with 100% achieving negative HCV RNA. Adverse events occurred in 57.7% of patients, including graft rejection (11.5%), delayed graft function (23.1%), and bleeding (11.5%), but none were related to the medication. Renal function remained stable, indicating the treatment was effective and safe. ^{1 3 4 5 6}

Is sofosbuvir/velpatasvir safe for use in kidney transplant patients?

Research shows that sofosbuvir/velpatasvir is generally safe for kidney transplant patients, with no adverse events directly related to the medication. In a study, 57.7% of patients experienced some adverse events, but these were not linked to the treatment. ^{1 3 4 6 7}

Is the drug Epclusa a promising treatment for kidney failure patients receiving a hepatitis C kidney transplant?

The research articles focus on sofosbuvir and daclatasvir, not Epclusa (sofosbuvir/velpatasvir). However, they show that sofosbuvir-based treatments are effective and safe for kidney transplant patients with hepatitis C. This suggests that Epclusa, which also contains sofosbuvir, could be promising for similar patients. ^{1 2 5 8 9}

How is the drug Epclusa unique for kidney failure patients receiving hepatitis C kidneys?

Epclusa, which combines sofosbuvir and velpatasvir, is unique because it is a pangenotypic treatment, meaning it can treat all types of hepatitis C virus, and it is specifically designed to be effective and safe for patients with kidney issues, including those undergoing kidney transplantation. ^{1 2 5 8 9}

Research Team

Peter Reese, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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 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]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. 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]

4. England 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. [2022]

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

Generic sofosbuvir-based direct-acting antivirals in hepatitis C virus-infected patients with chronic kidney disease. [2022]

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

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease. [2020]

9. New Zealand 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. [2022]