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A Clinical Trial of Zutectra in Patients Who Recently Received a Liver Transplant (ZEUS)

Primary Purpose

Hepatitis B

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Zutectra
Sponsored by
Biotest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatitis B focused on measuring Prevention, Hepatitis B virus re-infection, HBV-DNA negative, Liver transplantation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent obtained prior to orthotopic liver transplantation (OLT) - not more than 3 months before OLT
  • Historical evidence within the last 4 weeks that HBV-DNA is undetectable at time point of signature of Informed Consent
  • Male and female patients (age 18-75 years)
  • Patients with the diagnosis of liver failure with hepatitis B infection
  • Patients undergoing liver transplantation or re-transplantation
  • HBsAg negative on day 7 or on day 14 after OLT
  • HBV-DNA undetectable at OLT
  • Serum HBs antibody concentration on day 7 or on day 14 after OLT ≥ 400 IU/l
  • Stable patient in a condition which in the opinion of the investigator would permit safe participation in the study
  • Willingness to fill out patient diary

Exclusion Criteria:

  • Re-transplantation due to viral recurrence
  • Positive HIV or HCV test at time of transplantation
  • HBV-DNA positive at OLT
  • Patients having received organs from HBsAg positive donors
  • Pregnancy or unreliable contraceptive measures or lactation period (females only)
  • Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction)
  • Known intolerance to proteins of human origin
  • Participation in another interventional clinical trial within 90 days before entering the study or during the study and/or previous participation in this study (except screening failures)
  • Suspicion of drug and/or alcohol abuse
  • Inability or lacking motivation to participate in the study
  • Employee or direct relative of an employee of the CRO, the study site, or Biotest

Sites / Locations

  • Hopital de la Croix Rousse
  • Hôpital Paul Brousse
  • Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
  • S. Orsola Hospital
  • Azienda ospedaliera "G. Brutzu" di Cagliari
  • Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia
  • Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia
  • Azienda Ospedialera Universitaria di Padova
  • Azienda Ospedaliero-Universitaria Pisana
  • Fondazione Policlinico Tor-Vergata U.O.C.
  • Molinette Hospital
  • Hospital Clinic de Barcelona
  • Hospital General Universitario Gregorio Maranon
  • Hospital 12 de Octubre
  • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • King's College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zutectra

Arm Description

Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.

Outcomes

Primary Outcome Measures

Trough levels of serum anti-HBs antibody concentrations

Secondary Outcome Measures

Hepatitis B related re-infections
The number of all patients with hepatitis B related infections will be assessed by monitoring of clinical signs, liver function and measurement of HBsAg and HBV-DNA.

Full Information

First Posted
May 15, 2013
Last Updated
March 24, 2015
Sponsor
Biotest
Collaborators
AMS Advanced Medical Services GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01856413
Brief Title
A Clinical Trial of Zutectra in Patients Who Recently Received a Liver Transplant
Acronym
ZEUS
Official Title
An Open, Prospective, Single Arm Study Investigating Efficacy and Safety of Human Hepatitis B Immunoglobulin Zutectra in Liver Transplanted Patients - the ZEUS Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotest
Collaborators
AMS Advanced Medical Services GmbH

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Patients who receive liver transplantation for hepatitis B virus (HBV) induced liver failure require longterm therapy to prevent HBV reinfection of the transplanted liver. The approved preventative treatment is a combination of antihepatitis B immunoglobulin (HBIg) and oral antiviral medication. In the first 6 months after liver transplantation, patients receive treatment with intravenous HBIg to maintain blood antihepatitis B (antiHBs)antibody concentrations above 100 IU/L, the level considered safe for preventing hepatitis B reinfection. Zutectra is an HBIg preparation for subcutaneous injection that is approved in the EU for the 'prevention of HBV reinfection in HBV DNA negative patients ≥ 6 months after liver transplantation for hepatitis B induced liver failure'. The purpose of this study is to show that earlier subcutaneous HBIg treatment with Zutectra after liver transplantation can prevent hepatitis B reinfection. Treatment with subcutaneous HBIg (Zutectra) at home is manageable for the majority of patients and is more convenient for patients compared to intravenous treatment that must take place in the hospital setting. Fourty patients will take part in the study at approximately 19 centres in UK, France, Italy and Spain. Patients who are eligible for the study will receive treatment with Zutectra for 24 weeks. During the study, the safety and effectiveness of Zutectra will be assessed by checking for symptoms of hepatitis B related infection, as well as monitoring blood levels of antiHBs antibodies and hepatitis B surface antigen (HBsAg).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Prevention, Hepatitis B virus re-infection, HBV-DNA negative, Liver transplantation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zutectra
Arm Type
Experimental
Arm Description
Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.
Intervention Type
Drug
Intervention Name(s)
Zutectra
Other Intervention Name(s)
Human hepatitis B Immunoglobulin, HBIg
Intervention Description
Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.
Primary Outcome Measure Information:
Title
Trough levels of serum anti-HBs antibody concentrations
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Hepatitis B related re-infections
Description
The number of all patients with hepatitis B related infections will be assessed by monitoring of clinical signs, liver function and measurement of HBsAg and HBV-DNA.
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Adverse Events
Description
The number of adverse events will be documented including safety laboratory parameters reported as AEs.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent obtained prior to orthotopic liver transplantation (OLT) - not more than 3 months before OLT Historical evidence within the last 4 weeks that HBV-DNA is undetectable at time point of signature of Informed Consent Male and female patients (age 18-75 years) Patients with the diagnosis of liver failure with hepatitis B infection Patients undergoing liver transplantation or re-transplantation HBsAg negative on day 7 or on day 14 after OLT HBV-DNA undetectable at OLT Serum HBs antibody concentration on day 7 or on day 14 after OLT ≥ 400 IU/l Stable patient in a condition which in the opinion of the investigator would permit safe participation in the study Willingness to fill out patient diary Exclusion Criteria: Re-transplantation due to viral recurrence Positive HIV or HCV test at time of transplantation HBV-DNA positive at OLT Patients having received organs from HBsAg positive donors Pregnancy or unreliable contraceptive measures or lactation period (females only) Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction) Known intolerance to proteins of human origin Participation in another interventional clinical trial within 90 days before entering the study or during the study and/or previous participation in this study (except screening failures) Suspicion of drug and/or alcohol abuse Inability or lacking motivation to participate in the study Employee or direct relative of an employee of the CRO, the study site, or Biotest
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Didier Samuel, Professeur
Organizational Affiliation
Hospital Paul Brousse, Centre Hepato-Biliaire
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital de la Croix Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Facility Name
Hôpital Paul Brousse
City
Villejuif
ZIP/Postal Code
94804
Country
France
Facility Name
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
S. Orsola Hospital
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Azienda ospedaliera "G. Brutzu" di Cagliari
City
Cagliari
ZIP/Postal Code
CA 09135
Country
Italy
Facility Name
Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia
City
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Azienda Ospedialera Universitaria di Padova
City
Padova
ZIP/Postal Code
35122
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Pisana
City
Pisa
ZIP/Postal Code
54124
Country
Italy
Facility Name
Fondazione Policlinico Tor-Vergata U.O.C.
City
Roma
ZIP/Postal Code
00133
Country
Italy
Facility Name
Molinette Hospital
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Clinical Trial of Zutectra in Patients Who Recently Received a Liver Transplant

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