HCV Prophylaxis Strategies for Kidney Transplant Recipients

(PREVENT-HCV Trial)

Recruiting at 8 trial locations

Overseen By Christine Durand, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Active HCV, Cirrhosis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2-12 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal timing for starting medication to prevent Hepatitis C in individuals receiving a kidney from a Hepatitis C-positive donor. Participants will be divided into two groups: one group will begin the Hepatitis C medication (Prophylaxis, also known as Sofosbuvir/Velpatasvir or Epclusa) two weeks before the transplant, while the other group will start the medication (Transmit and Treat, which includes Direct-acting Antivirals for HCV like Sofosbuvir/Velpatasvir, Ledipasvir/Sofosbuvir, or Elbasvir/Grazoprevir) after the transplant, continuing it for twelve weeks. The study seeks individuals who are HCV-negative, eligible for a kidney transplant, and able to provide informed consent. As an unphased trial, it offers a unique opportunity to contribute to medical knowledge and potentially improve transplant outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are unable to safely stop or switch a medication that conflicts with the study medication.

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

Research shows that the treatments tested in this trial are generally well-tolerated by patients. For the Prophylaxis group, studies have found that using sofosbuvir/velpatasvir before and after a kidney transplant is safe for individuals without Hepatitis C. No major safety issues were reported, and the treatment effectively prevented infections.

For the Transmit and Treat strategy, research indicates that the medications used in this trial, known as direct-acting antivirals (DAAs), are generally safe and effective. In kidney transplant patients, these medications have a high success rate in curing Hepatitis C without causing major side effects. Both treatment options in the trial have a good safety record based on previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for kidney transplant patients at risk of Hepatitis C (HCV) infection because they offer innovative approaches to prevention and management. The Prophylaxis (P2W) strategy involves administering sofosbuvir/velpatasvir (SOF/VEL) before the transplant and continuing for two weeks, potentially reducing the risk of HCV transmission during this critical period. On the other hand, the Transmit and Treat (T&T) strategy starts the SOF/VEL regimen as soon as possible post-transplant, allowing for treatment flexibility based on insurance approvals or within two weeks, whichever comes first. Both strategies leverage the combination of SOF/VEL, known for its efficacy and safety, offering new hope for preventing and managing HCV in kidney transplant recipients.

What evidence suggests that this trial's treatments could be effective for HCV in kidney transplant recipients?

Research has shown that the combination of sofosbuvir and velpatasvir (SOF/VEL) effectively prevents and treats Hepatitis C Virus (HCV) in kidney transplant patients. In this trial, participants may receive one of two strategies. The "Prophylaxis (P2W)" approach, where SOF/VEL is used briefly before the transplant, has lowered HCV transmission rates to about 13% in studies. Alternatively, the "Transmit and Treat (T&T)" method involves using direct-acting antivirals like SOF/VEL after the transplant, curing HCV in 97% of kidney transplant recipients. Overall, these treatments are both effective and safe for those receiving kidneys from donors with HCV. ^{1 2 3 5 6}

Who Is on the Research Team?

Christine Durand, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need a kidney transplant and can give informed consent. They must meet standard criteria for transplantation, have normal liver function (AST or ALT within safe limits), and not be infected with HIV, active hepatitis B, or have had hepatitis C. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

I meet the kidney transplant criteria at my local center.

I understand the study and can give my consent.

Exclusion Criteria

I have a history of hepatitis C.

I have a liver condition with a FIB-4 score of 1.45 or higher, or a history of severe liver scarring.

I cannot stop or change a medication I'm taking that's not allowed with the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sofosbuvir/velpatasvir (SOF/VEL) for either 2 weeks starting pre-transplant (prophylaxis) or 12 weeks starting post-transplant (transmit-and-treat)

2-12 weeks

Follow-up

Participants are monitored for safety, effectiveness, and various health outcomes post-transplant

At least 6 months, up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Prophylaxis (P2W)
• Transmit and Treat (T&T)

Trial Overview The study compares two timings to start Hepatitis C medication in patients receiving kidneys from HCV-positive donors: 'Prophylaxis' starts treatment before the transplant with a shorter course of medication; 'Transmit and Treat' begins after the transplant with a full course.

How Is the Trial Designed?

Group I: Transmit and Treat (T&T) Experimental Treatment 1 Intervention

T\&T is study-supplied SOF/VEL for 12 weeks starting on post-HCV D+/R- kidney transplant day participant's insurance approves standard of care DAAs, or post-KT day 14, whichever comes first.

Group II: Prophylaxis (P2W) Experimental Treatment 1 Intervention

Prophylaxis is one dose of sofosbuvir/velpatasvir (SOF/VEL) pre-HCV D+/R- kidney transplant (KT), continued for 2 weeks.

Prophylaxis (P2W) is already approved in United States, European Union for the following indications:

Approved in United States as Epclusa for:

• Chronic hepatitis C virus (HCV) infection
• Prevention of HCV transmission in HCV-negative recipients of HCV-positive organ transplants

Approved in European Union as Epclusa for:

• Chronic hepatitis C virus (HCV) infection
• Prevention of HCV transmission in HCV-negative recipients of HCV-positive organ transplants

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a pilot study involving 25 kidney transplant recipients, a sofosbuvir-based regimen demonstrated high efficacy, with 88% of patients achieving a rapid virological response by week 4 and all patients having undetectable HCV RNA by the end of therapy.

The treatment was well-tolerated with no adverse events reported, indicating that new-generation direct antiviral agents (DAAs) are both effective and safe for treating hepatitis C virus infection in kidney transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sofosbuvir-Based Antiviral Therapy to Treat Hepatitis C Virus Infection After Kidney Transplantation. Kamar, N., Marion, O., Rostaing, L., et al.[2023]

In a study of 22 HCV-infected renal transplant recipients treated with sofosbuvir-based regimens, there was a remarkable 100% sustained viral response at both 12 and 24 weeks, indicating high efficacy of the treatment.

The treatment was generally safe, although ribavirin caused anemia in some patients, and there was a notable decrease in tacrolimus levels, necessitating dose adjustments for many participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct-acting Antiviral Agents in Hepatitis C Virus-infected Renal Allograft Recipients: Treatment and Outcome Experience from Single Center. Prasad, N., Patel, MR., Pandey, A., et al.[2020]

Sofosbuvir-based therapy demonstrated 100% effectiveness in treating chronic hepatitis C virus infection in 40 stable kidney transplant recipients, with successful virologic responses at all assessed time points.

While the treatment was safe overall, it significantly reduced hemoglobin levels in half of the patients, necessitating careful monitoring and potential dose adjustments of ribavirin, as well as a notable decrease in calcineurin inhibitor levels during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of sofosbuvir-based therapy against chronic hepatitis C infection after successful kidney transplantation. Musialik, J., Kolonko, A., Kwiecień, K., et al.[2019]

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 30 patients with chronic hepatitis C genotype 1, treatment with generic sofosbuvir/ledipasvir (SOF/LDV) resulted in a 100% sustained virologic response, indicating its high efficacy in clearing the virus.

The treatment was found to be safe, with no severe adverse events reported, although 20% of patients experienced mild to moderate side effects, demonstrating that generic SOF/LDV is a viable option even for patients with cirrhosis or previous interferon treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life efficacy of generic sofosbuvir/ledipasvir for treatment of Iranian patients with chronic hepatitis C: A cohort study. Sharafi, H., Alavian, SH., Behnava, B., 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 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]

A 7-day prophylaxis with sofosbuvir/velpatasvir (SOF/VEL) significantly reduced hepatitis C virus (HCV) transmission in kidney transplant recipients from infected donors, with only 4% of patients experiencing transmission compared to 13% with a 2- to 4-day protocol.

All patients who developed HCV transmission achieved a sustained virologic response after full-course therapy, indicating effective treatment outcomes, and there were no significant differences in transplant outcomes between HCV-positive and HCV-negative recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants. Gupta, G., Yakubu, I., Zhang, Y., et al.[2023]

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. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522088050

Outcomes of short-duration antiviral prophylaxis for ... We previously reported HCV transmission of 13% among D+/R– transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis ...

4. 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].

5. 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 ...

6. 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. ...