Preemptive Zepatier Treatment in Donor HCV Positive to Recipient HCV Negative Cardiac Transplant

A Proof of Concept Study for Preemptive Treatment With Grazoprevir and Elbasvir in Donor HCV-positive to Recipient HCV-negative Cardiac Transplant

This is a proof of concept, single center study for the donation of HCV-positive hearts to HCV negative recipient patients, with preemptive, interventional treatment with 12-16 weeks of grazoprevir and elbasvir (with or without ribavirin) to prevent HCV transmission upon transplantation.

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C; Cardiac Transplant Disorder
• Intervention / Treatment: Drug: Combindation treatment with Grazoprevir and Elbasvir fixed dose combination tablet, with or without ribavirin

Detailed Description

Phase 1 of this study will be a single case study with only one subject enrolled. Once safety has been demonstrated and HCV infection transmission shown to be prevented by the protocol, the study will expand to 10 additional patients.

Patients will be selected based on their diminished likelihood of receiving a heart from the waitlist within a period during which they would be likely to succumb to severe comorbidities. This will be determined in part through use of a patient's listing status (1A, 1B, 2) and clinical judgment, and the Seattle Heart Failure Model.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Masschusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recipient is Age ≥ 18 years
• Serum ALT within normal limits with no history of liver disease
• Lack of sensitization (i.e. PRA < 20%) that would be expected to result in a high likelihood of needing aggressive immunosuppression to treat rejection

Exclusion Criteria:

• Sensitization (i.e. PRA >20%)
• Any liver disease in recipient
• Albumin < 3g/dl or platelet count < 75 x 103/mL
• Need for dual organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with grazoprevir + elbasvir +/- ribavirin; 12 to 16 weeks of treatment with combination tablet of grazoprevir + elbasvir +/- ribavirin	Drug: Combindation treatment with Grazoprevir and Elbasvir fixed dose combination tablet, with or without ribavirin; HCV treatment for 12 to 16 weeks. Treatment length and addition of ribavirin based upon presence of baseline resistance associated variant in the HCV virus. Medications given concurrently.; Other Names: Zepatier

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable HCV	Negative HCV viral RNA at 12 weeks after the last dose of treatment.	12 Weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability (based on number of adverse events and out of range lab values) of grazoprevir and elbasvir (with or without ribavirin) in patients who have undergone cardiac transplantation	Safety and tolerability of grazoprevir and elbasvir in the cardiac transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient.	Upto 16 Weeks

Collaborators and Investigators

• Sponsor: Raymond T. Chung, MD
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 19, 2017
• First Posted (Estimate): January 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Hepatitis C; Heart Transplant; Cardiac Transplant; Zepatier
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Grazoprevir
• Other Study ID Numbers: 2017P000074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified patient data will be shared with research collaborators for safety and data analysis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No