Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-negative Recipients

NCT02781649 | Completed Phase 4 Results

• 1 other identifier: IRB00089751
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

End-Stage Renal Disease; Hepatitis C

Keywords

Renal; Transplants; Hepatitis C; HCV-negative; Infected; Donors

Outcome Measures

Primary Outcomes (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

  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 Outcomes (6)

• Viral Response

  12 weeks after completing treatment

• Antibody Development

  12 weeks

• Number of Participants With Nonstructural Protein 5A (NS5A) Resistance Mutations in the HCV Population From the Deceased Donors

  Baseline

• IP-10 Elevations

  12 weeks

• Kidney Function at 6 Months

  6 months following transplantation

Study Arms (3)

Donor genotype 1a no resistance or 1b

EXPERIMENTAL

Participants who receive donors found to have hepatitis C genotype 1a without resistance Zepatier one tablet daily for 12 weeks

Drug: Zepatier

Donor genotype 1a with resistance

EXPERIMENTAL

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; Drug: Ribavirin

Donor genotype 2 or 3

EXPERIMENTAL

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; Drug: Sofosbuvir

Interventions

Zepatier DRUG

Fixed dose Grazoprevir 100 mg/Elbasvir 50 mg by mouth daily for 12 weeks

Also known as: Fixed dose Grazoprevir /Elbasvir

Donor genotype 1a no resistance or 1b; Donor genotype 1a with resistance; Donor genotype 2 or 3

Ribavirin DRUG

Ribavirin 1200 mg/d (\> 75 kg) or 1000 mg/d (\< 75 kg) by mouth daily in two divided doses

Also known as: Rebetol, Copegus, Virazole, and Ribasphere

Donor genotype 1a with resistance

Sofosbuvir DRUG

Sofosbuvir 400 mg daily

Also known as: Sovaldi

Donor genotype 2 or 3

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6.

  PMID: 29507971 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; grazoprevir; elbasvir; Ribavirin; Sofosbuvir

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Christine Durand, MD
• Organization: Johns Hopkins University

cdurand2@jhmi.edu

410-955-5684

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 24, 2016
• Study Start: July 20, 2016
• Primary Completion: May 3, 2017
• Study Completion: January 1, 2018
• Last Updated: September 6, 2018
• Results First Posted: April 5, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)