HCV-Positive Organ Transplant Safety

Overseen By Nellie Kamkar, MSc

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Jordan Feld

Must be taking: Direct-acting antivirals

Disqualifiers: Chronic liver disease, other trial, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether organs from donors with hepatitis C (HCV) can be safely transplanted into patients without HCV. Recipients will take antiviral drugs, Glecaprevir/Pibrentasvir, and another drug, ezetimibe, before the transplant to prevent HCV infection. The study aims to demonstrate that these drugs can either prevent HCV transmission to the recipient or make it easy to treat if transmission occurs. Suitable candidates include those awaiting a kidney, pancreas, heart, or lung transplant who do not have HCV. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

Research has shown that the antiviral combination of Glecaprevir/Pibrentasvir (G/P) safely prevents the spread of hepatitis C from infected organ donors to uninfected recipients. In one study, a 7-day course of G/P started before surgery successfully prevented hepatitis C in all 10 cases tested, indicating that the treatment is well-tolerated.

Ezetimibe, a cholesterol-lowering drug, was also tested with G/P to block hepatitis C from entering cells. Studies show that this combination helps prevent long-term hepatitis C infection after organ transplants and does not cause serious side effects.

In summary, both G/P and Ezetimibe have strong safety records and are expected to be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatment of using glecaprevir/pibrentasvir in HCV-positive organ transplants because it offers a targeted antiviral approach that could enhance the safety of transplants from HCV-positive donors. Unlike standard antiviral treatments, this combination is administered in a short course of eight doses and targets multiple stages of the hepatitis C virus life cycle, potentially reducing the risk of HCV transmission to recipients. Additionally, for lung transplants, donor lungs are preserved and treated using normothermic ex vivo lung perfusion (EVLP), a method that helps repair and assess lungs under protective conditions, which is not a common practice in current transplant protocols. This dual approach of antiviral treatment and innovative lung preservation may significantly improve outcomes for recipients.

What evidence suggests that this trial's treatments could be effective for HCV-positive organ transplant safety?

Research has shown that the drug combination glecaprevir/pibrentasvir effectively treats hepatitis C. Studies have found that patients using this combination often have no detectable virus in their system 12 weeks after treatment, indicating the virus is no longer a problem for them. In this trial, all transplant recipients will receive glecaprevir/pibrentasvir alongside ezetimibe. Early evidence suggests that adding ezetimibe can help prevent long-term hepatitis C infection in people who have had organ transplants. This short treatment regimen aims to stop the virus from taking hold initially, potentially making organ transplants from donors with hepatitis C both safe and successful. ^{1 2 3 6 7}

Who Is on the Research Team?

Jordan Feld, MD, MPH

Principal Investigator

University Health Network Toronto General Hospital

Are You a Good Fit for This Trial?

This trial is for individuals under the age of 70 who need an organ transplant and are willing to receive organs from donors with Hepatitis C, using antiviral prophylaxis. It's not suitable for those outside this age range or those who may have conditions that could interfere with the study.

Inclusion Criteria

I am younger than 70 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Antiviral Prophylaxis

Participants receive an initial dose of antiviral prophylaxis using Glecaprevir/Pibrentasvir and ezetimibe prior to transplantation

1 day

Transplantation and Immediate Post-Transplant Treatment

Participants undergo organ transplantation and receive daily doses of Glecaprevir/Pibrentasvir and ezetimibe for 7 days post-transplant

1 week

Follow-up

Participants are monitored for safety, HCV transmission, and organ function with blood samples taken daily for the first 2 weeks and then weekly until 12 weeks post-transplant

12 weeks

Long-Term Follow-up

Participants are monitored for long-term organ function and HCV seroconversion up to 1 year post-transplant

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ezetimibe
• Glecaprevir/Pibrentasvir

Trial Overview The trial tests if it's safe to transplant organs from Hepatitis C positive donors into recipients without the virus by giving them antivirals (Glecaprevir/Pibrentasvir) and a cholesterol drug (Ezetimibe) that also blocks HCV entry into cells before and after surgery.

How Is the Trial Designed?

Group I: Non Randomized Intervention Experimental Treatment 3 Interventions

Intervention description: recipients on the wait-list for lung, heart, kidney, and/or pancreas transplants will all receive antiviral treatment in the form of 8 total doses of oral tablets. Lung recipients will also receive donor lungs that are treated with normothermic EVLP (details of both described below). Drug: All recipients will receive glecaprevir (300mg)/pibrentasvir (120mg) supplied as three tablets per dose 6-12 hours prior to transplant, and for 7 days post-transplant. Other Names: Maviret. Patients will also receive ezetimibe (10mg), supplied as one tablet per dose to be taken at the same time as Maviret tablets (6-12 hours prior to transplant in addition to 7 daily doses post-transplant). Ex Vivo Lung Perfusion (EVLP): Normothermic EVLP is a method of donor lung preservation, assessment, treatment, and repair of injured organs. This method allows donor lungs to be treated for at least 12h under protective physiological conditions. Other names: Normothermic EVLP.

Who Is Running the Clinical Trial?

Jordan Feld

Lead Sponsor

Trials

2

Recruited

3,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7391837/

Evaluation of short-course direct-acting antivirals and ... Ezetimibe combined with glecaprevir/pibrentasvir given one dose before and for 7 days after transplant prevented establishment of chronic HCV infection in ...

2. jhltonline.org jhltonline.org/article/S1053-2498(24)00159-1/fulltext

Efficacy of Short Course Direct Acting Antivirals and ... Shorter duration of 14 doses of DAA plus HCV entry blocker is safe and effective at preventing persistent HCV viremia in heart and lung transplant recipients.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125320300819

Articles Short-course, direct-acting antivirals and ezetimibe ... This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10567032/

Real-world Experiences in the Transplantation of Hepatitis ... We present data from a single major transplant center describing our real-world experience with HCV-NAAT–positive organ transplantation to HCV- ...

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

Outcomes of short-duration antiviral prophylaxis for ... We report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R– transplants (N = 102).

6. amjtransplant.org amjtransplant.org/article/S1600-6135(23)00796-7/fulltext

Outcomes of early vs late treatment initiation in solid organ ... Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer ...

7. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-022-02107-1

Hepatitis C positive organ transplantation to negative ... Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft ...