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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02781649
Recruitment Status : Completed
First Posted : May 24, 2016
Results First Posted : April 5, 2018
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Johns Hopkins University

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
End-Stage Renal Disease Hepatitis C Drug: Zepatier Drug: Ribavirin Drug: Sofosbuvir Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 20, 2016
Actual Primary Completion Date : May 3, 2017
Actual Study Completion Date : January 1, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: Fixed dose Grazoprevir /Elbasvir

Drug: Sofosbuvir
Sofosbuvir 400 mg daily
Other Name: Sovaldi


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Antibody Development [ Time Frame: 12 weeks ]
    Number of kidney transplant recipients who become reactive for HCV antibody

  3. 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


  4. IP-10 Elevations [ Time Frame: 12 weeks ]
    Measurement of interferon (IFN)-gamma inducible protein 10 (IP-10) a marker of acute hepatitis C infection.

  5. Kidney Function at 6 Months [ Time Frame: 6 months following transplantation ]
    Serum creatinine mg/dL at 6 months following transplantation

  6. Kidney Function at 12 Months [ Time Frame: 12 months following transplantation ]
    Serum creatinine mg/dL at 12 months following transplantation


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02781649


Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins University
Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:
Study Protocol and Statistical Analysis Plan  [PDF] April 11, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02781649    
Other Study ID Numbers: IRB00089751
First Posted: May 24, 2016    Key Record Dates
Results First Posted: April 5, 2018
Last Update Posted: September 6, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Peer reviewed publications
Keywords provided by Johns Hopkins University:
Renal
Transplants
Hepatitis C
 HCV-negative
Infected
Donors
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis
Kidney Failure, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
 Flaviviridae Infections
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Ribavirin
Sofosbuvir
Grazoprevir
Elbasvir-grazoprevir drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents