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Zepatier/Trial Underway for Hep C-Positive Kidney Transplants
  DECEMBER 14, 2016
By Gina Shaw
Several patients have now been treated in two first-of-their-kind clinical trials involving kidney transplants from donors who had hepatitis C virus (HCV), according to investigators at the University of Pennsylvania who are leading one of the trials (the other is at Johns Hopkins University).
Typically, when an organ donor has HCV, all of the person's organs are discarded, but the advent of new hepatitis C medications offering a nearly 100% cure rate has opened up the possibility that these organs could be used after all.
In the trial, known as THINKER, 10 patients at both institutions will receive kidney transplants from donors who were infected with HCV. After transplant, they will undergo a full 12-week course of treatment with elbasvir-grazoprevir (Zepatier, Merck). That regimen was chosen because a subset of kidney transplant patients do not immediately recover full kidney function and require a period of dialysis, and elbasvir-grazoprevir has been demonstrated as safe for dialysis patients.
Merck is providing the drug for free in both trials, as well as funding other components of the research.
Two trial participants have given the investigators full permission to discuss their cases with the media, David Goldberg, MD, an assistant professor of medicine and a transplant specialist at the University of Pennsylvania in Philadelphia, and a lead investigator in the trial, told Specialty Pharmacy Continuum. "The first patient, who received her transplant in July, has already completed the full 12 weeks of treatment with Zepatier. Seven weeks after completing the regimen, she has no detectable viral load, has normal kidney function and is enjoying life. We can't call her cured until 12 weeks after completion of treatment, but things are looking good."
The other patient who gave permission for his case to be discussed completed his course of treatment with elbasvir-grazoprevir on Nov. 1, and has undetectable levels of the virus at this point as well. "I can't say how many other patients have been transplanted at this point, but everyone in the trial so far is doing well," Dr. Goldberg noted. About 100,000 people are currently on the waiting list for a donor kidney, with a median wait time of about 3.5 years. Approximately 5% of the people on the waiting list die each year. The researchers estimate that at least 500 additional transplants could be performed each year if their trial is successful.
Penn Medicine transplants Hepatitis C-infected kidneys in clinical trial
News Release
September 13, 2016
Expanding Access: First Clinical Trial Transplants Hepatitis C-Infected Kidneys at Penn
Clinical trial tests the effect of giving organ recipients antiviral therapy after being transplanted with kidneys that otherwise go unused

PHILADELPHIA - Patients who need a kidney transplant may have new hope, through an innovative Penn Medicine clinical trial using kidneys from deceased donors who had the Hepatitis C virus (HCV). The first study participant received a kidney transplant in July 2016, and after being treated with a full regimen of Zepatier - a recently-approved oral medication prescribed to eradicate HCV - her doctors announced today that there is no evidence of the virus in her blood. Irma Hendricks of East Stroudsburg, PA, faced upwards of five years on the transplant waiting list with dialysis three days a week for many hours, before enrolling and receiving a kidney transplant as part of this trial. The research team says if the new approach works, for patients who do not have HCV, there is the potential to provide a chance at a lifesaving kidney transplant for hundreds more patients each year.
The clinical trial, known as THINKER, led by David S. Goldberg, MD, MSCE, and Peter Reese, MD, MSCE, both assistant professors of Medicine and Epidemiology at Penn, aims to determine the safety and efficacy of transplanting kidneys from Hepatitis C-positive donors into patients currently on the kidney transplant waitlist who do not have the Hepatitis C virus.
"There are more than 99,000 Americans are awaiting a kidney transplant," said Reese, who is also an assistant professor of Medical Ethics and Health Policy at Penn and chair of the Ethics Committee for the United Network of Organ Sharing (UNOS). "Yet despite very long waiting times for transplant, hundreds of otherwise good kidneys from deceased donors infected with Hepatitis C are discarded each year. If we can demonstrate that it's possible to eradicate HCV from patients who contract the virus from a transplant, this approach could open up access to an entirely new pool of donor organs that are currently being discarded. Ultimately, our hope is that this trial will show that it is possible, and will then afford far more patients who are on the waiting list an opportunity to receive a lifesaving transplant much sooner."
Reese and Goldberg estimate that if this experimental course of transplantation and treatment proves effective in the long term, at least 500 more kidneys could become available for transplantation each year. Currently, individuals who have Hepatitis C are only eligible to donate organs to recipients who also have the virus. But in most cases, these HCV-infected organs would be discarded, and never used for transplantation. The study is enrolling patients between 40 and 65 years of age, with a Blood type A, B, or O, with varying ethnicities and socioeconomic statuses, who do not have Hepatitis C and are receiving chronic dialysis, a treatment that often causes severe fatigue and medical complications and can require a tremendous time investment. Typically, patients must undergo dialysis to filter their blood often three or more times a week, for upwards of three hours each session. Though many patients who receive kidney transplants are able to obtain a donor organ from a relative or matching unrelated donors, thousands have no such option and can wait years for a kidney to become available from a suitable, deceased donor. After a rigorous informed consent process, participants in the new Penn study are enrolled and eligible to receive kidneys from donors with Hepatitis C.
In this study, only donated kidneys that are infected with a certain strain of HCV are used. There are six genotypes of HCV that have been identified, but patients will only receive HCV genotype 1-infected kidneys, since the viral treatment used in this study has a 95 percent success rate in eradicating this type of HCV in the general population. Additional steps are taken to ensure that the kidneys study participants receive are high quality, with the best possible chance of successful transplant.
"While these kidney quality criteria may be more selective than our usual approach to choosing organs, we are aiming to evaluate safety and efficacy in only the most viable organs in this initial pilot phase of the clinical trial," said Goldberg, who is also the medical director for Living Donor Liver Transplantation at Penn. "We realized that the amazing transformation of treatment options for Hepatitis C should also transform how we think about organs with Hepatitis C. At this very early point in the study, we are pleased with how our first patients have responded to transplantation and antiviral treatment." Researchers intend to transplant and treat 10 patients in this pilot study. Patients who receive an HCV-infected kidney, who are then treated with an extended regimen of Zepatier, can be classified as HCV-free or "cured" if they have undetectable levels of the virus three months after completion of the oral medication. One risk of participating in this clinical trial, which is discussed during the informed consent process, is that patients who receive the HCV-positive kidney may become infected with the Hepatitis C, and may never be cleared of the virus despite the medication regimen.
There are an estimated 3.9 million Americans living with the Hepatitis C virus, a contagious viral disease that causes inflammation of the liver and can range in severity from mild illness lasting a few weeks to a lifelong disease leading to weakened liver function or liver failure. HCV often goes unnoticed as many of those infected don't show symptoms until significant liver damage is detected. Those with ongoing HCV can develop cirrhosis - scarring of the liver - leading to complications such as bleeding, yellowing of the skin or eyes, fluid buildup, infections and even liver cancer. New treatments for Hepatitis C approved over the past several years have high cure rates and much better side effect profiles than historical treatment options.
Additional Penn Medicine experts involved in this study span disciplines including infectious diseases, transplantation surgery, gastroenterology, hepatology, and pathology and laboratory medicine, including Deirdre Sawinski, Roy Bloom, Raj Reddy, Emily Blumberg, Jennifer Trofe-Clark, Vivianna Van Deerlin, Midhat Farooqi, Peter Abt, Matthew Levine, Paige Porrett, Susanna Nazarian, Ali Naji, Maureen McCauley, and Anna Sicilia. The study is supported by a research grant from the Merck Investigator Initiated Studies Program. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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