Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients (EXPANDER-1)

August 8, 2018 updated by: Johns Hopkins University

An Open-label Pilot Study to Determine the Tolerability and Efficacy of Fixed-dose Grazoprevir/Elbasvir Treatment in Hepatitis C Uninfected Recipients of Renal Transplants From Hepatitis C Infected Deceased Donors

In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include Grazoprevir (GZR) 100 mg/Elbasvir (EBR) 50 mg administered on-call to the operating room for the renal transplant procedure and continued for 12 weeks post-renal transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Hepatitis C treatment will include Grazoprevir (GZR) 100 mg/Elbasvir (EBR) 50 mg administered on-call to the operating room for the renal transplant procedure and continued for 12 weeks post-renal transplant. The donor hepatitis C genotype will be tested. If the donor has genotype 1a without resistance or genotype 1b treatment will remain GZR/EBR for 12 weeks. If the donor has genotype 1a with resistance variants, then Ribavirin will be added and treatment will be given for 16 weeks starting from the date ribavirin was added. If the donor has hepatitis C genotype 2 or 3, Sofosbuvir will be added and treatment will be for 12 weeks from the date Sofosbuvir was added.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants ≥ 50 years old
  • On the deceased donor kidney waiting list at Johns Hopkins Hospital
  • Awaiting a first kidney transplant
  • No available living kidney donors
  • On hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min for ≥ past 90 days
  • HCV-uninfected (by both antibody and RNA PCR) and without any behavioral risk factors for contracting HCV other than being on hemodialysis.
  • Calculated panel reactive anti-human leukocyte antigen (HLA) antibody (cPRA) below 20 percent

  • Female who is:

    • practicing total abstinence from sexual intercourse (minimum 1 complete menstrual cycle)
    • sexually active with female partners only
    • not of childbearing potential: defined as postmenopausal for at least 2 years prior to screening defined as amenorrheic for longer than 2 years, age appropriate, and confirmed by a follicle-stimulating hormone level indicating a postmenopausal state, or surgically sterile: defined as bilateral tubal ligation, bilateral oophorectomy or hysterectomy or has a vasectomized partner(s);
    • of childbearing potential and sexually active with male partner(s): currently using at least one effective method of birth control at the time of screening and agree to practice two effective methods of birth control while receiving study drug (as outlined in the participant information and consent form starting with Study Day 1 and for 30 days after stopping study drug, or for 6 months after stopping study drug if receiving RBV (Note: Estrogen-containing hormonal contraceptives, including oral, injectable, implantable, patch and ring varieties, may not be used during study drug treatment).
  • Males who are not surgically sterile and are sexually active with female partner(s) of childbearing potential must agree to practice two effective forms of birth control (as outlined in the participant information and consent form) throughout the course of the study, starting with starting with Study Day 1 and for 30 days after stopping study drug, or for 6 months after stopping study drug if receiving ribavirin (RBV)

Exclusion Criteria:

  • Plan to receive a multi-organ transplant
  • Plan to receive a dual kidney transplant (including en bloc)
  • Prior solid organ transplant
  • Participating in another study that involves an intervention or investigational product
  • Plan to receive a blood type incompatible kidney
  • History of human immunodeficiency (HIV), hepatitis C (HCV), or active hepatitis B (HBV) infection defined as being on active antiviral treatment for HBV, detectable hepatitis B surface Ag or detectable hepatitis B DNA
  • Active or unresolved bacterial, viral, or fungal infection that is clinically significant
  • History of cirrhosis or pre-existing liver disease such as non-alcoholic steatohepatitis
  • History of illicit drug use or alcohol abuse within 12 months prior to screening
  • Psychiatric or physical illness that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donor genotype 1a no resistance or 1b
Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks
Drug: Zepatier
Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks
Other Names:
  • Fixed dose Grazoprevir /Elbasvir
Experimental: Donor genotype 1a with resistance
Participants who receive donors found to have hepatitis C genotype 1a with nonstructural protein 5A associated resistance mutations Zepatier one tablet daily for 16 weeks Ribavirin weight based dosing for 16 weeks
Drug: Zepatier
Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks
Other Names:
  • Fixed dose Grazoprevir /Elbasvir
Drug: Ribavirin
Ribavirin 1200 mg/d (> 75 kg) or 1000 mg/d (< 75 kg) by mouth daily in two divided doses
Other Names:
  • Rebetol, Copegus, Virazole, and Ribasphere
Experimental: Donor genotype 2 or 3
Participants who receive donors found to have hepatitis C genotype 2 or 3 Zepatier one tablet daily for 12 weeks Sofosbuvir 400 mg daily for 12 weeks
Drug: Zepatier
Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks
Other Names:
  • Fixed dose Grazoprevir /Elbasvir
Drug: Sofosbuvir
Sofosbuvir 400 mg daily
Other Names:
  • Sovaldi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Grade 3 or Higher Treatment-related Adverse Events as US Department of Health and Human Services Common Terminology of Adverse Events (CTCAE) Version 4
Time Frame: 12 weeks after transplant
Proportion of participants with grade 3 or higher treatment-related adverse events (AE) as assessed by US Department of Health and Human Services Common Terminology of AEs version 4. An AE is an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5. Grade 3 Severe or medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. The investigator will determine if the AE is related to the treatment.
12 weeks after transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viral Response
Time Frame: 12 weeks after completing treatment
This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 12
12 weeks after completing treatment
Antibody Development
Time Frame: 12 weeks
Number of kidney transplant recipients who become reactive for HCV antibody
12 weeks
Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors
Time Frame: Baseline

Number of participants with NS5A resistance mutations in the HCV population from the deceased donors.

Number of donors with NS5A resistance mutations
Baseline
IP-10 Elevations
Time Frame: 12 weeks
Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection.
12 weeks
Kidney Function at 6 Months
Time Frame: 6 months following transplantation
Serum creatinine mg/dL at 6 months following transplantation
6 months following transplantation
Kidney Function at 12 Months
Time Frame: 12 months following transplantation
Serum creatinine mg/dL at 12 months following transplantation
12 months following transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2016

Primary Completion (Actual)

May 3, 2017

Study Completion (Actual)

January 1, 2018

Study Registration Dates

First Submitted

May 10, 2016

First Submitted That Met QC Criteria

May 23, 2016

First Posted (Estimate)

May 24, 2016

Study Record Updates

Last Update Posted (Actual)

September 6, 2018

Last Update Submitted That Met QC Criteria

August 8, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00089751

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Peer reviewed publications

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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