Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients

NCT03249194 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: HM20010320
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus (HCV) has changed the landscape of HCV therapy dramatically in the last several years with reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV positive patients including those who have received liver or kidney transplants. Since these new regimens do not include interferon and have already been studied in the post-liver and kidney transplant setting, they now offer a unique opportunity to expand the donor pool and improve the lives of those awaiting renal transplant. The address this gap in knowledge, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable risks and improved survivals compared with historical cohorts.

Conditions

Kidney Transplant; Hepatitis C

Outcome Measures

Primary Outcomes (2)

• Sustained Virologic Response (SVR)

  Among the patients who develop HCV viremia SVR rates with DAA will be measured

  12 weeks

• Graft and Patient Survival

  Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice

  1 year

Secondary Outcomes (3)

• Sustained Virologic Response (SVR) Follow Up 1

  24 weeks

• Sustained Virologic Response (SVR) Follow Up 2

  48 weeks

• Liver Disease

  1 year

Study Arms (1)

HCV+ Donor Kidney Recipient

EXPERIMENTAL

All HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant. Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks.

Drug: Direct acting Anti-Viral Therapy using Epclusa or Zepatier

Interventions

Direct acting Anti-Viral Therapy using Epclusa or Zepatier DRUG

All patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results

Also known as: Epclusa, Zepatier

HCV+ Donor Kidney Recipient

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• No evidence of HCV infection by HCV PCR (done at the time of the initial consent)
• Age\>60 yrs with an expected waiting time\>2 years; or
• Age\<60 yrs with any one of the following risk factors: Diabetes, coronary artery disease, peripheral artery disease and/or cerebrovascular disease
• Willingness to provide informed consent
• Absence of a living donor.

You may not qualify if:

• Estimated life expectancy of less than one year based on clinical judgment of the investigator
• Prior liver or renal transplantation
• Pregnant women
• Incarcerated patients
• Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
• Unable or unwilling to return for follow-up visits
• HBV sAg positive
• HIV PCR or antibody positive
• HCV RNA negative

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Gupta G, Yakubu I, Bhati CS, Zhang Y, Kang L, Patterson JA, Andrews-Joseph A, Alam A, Ferreira-Gonzalez A, Kumar D, Moinuddin IK, Kamal L, King AL, Levy M, Sharma A, Cotterell A, Reichman TW, Khan A, Kimball P, Stiltner R, Baldecchi M, Brigle N, Gehr T, Sterling RK. Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients. Am J Transplant. 2020 Mar;20(3):739-751. doi: 10.1111/ajt.15664. Epub 2019 Nov 15.

  PMID: 31652392 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Gaurav Gupta, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: August 15, 2017
• Study Start: August 17, 2017
• Primary Completion: March 15, 2020
• Study Completion: March 15, 2020
• Last Updated: March 27, 2020

Record last verified: 2020-03

Locations

US (1)