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

An Open, Prospective, Single Arm Study Investigating Efficacy and Safety of Human Hepatitis B Immunoglobulin Zutectra in Liver Transplanted Patients - the ZEUS Study

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).

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Zutectra

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69004
    • Hôpital de La Croix Rousse
  • Villejuif, France, 94804
    • Hopital Paul Brousse
• Italy
  • Bari, Italy, 70124
    • Azienda ospedaliero-universitaria consorziale policlinico di Bari
  • Bologna, Italy, 40138
    • S. Orsola Hospital
  • Cagliari, Italy, CA 09135
    • Azienda ospedaliera "G. Brutzu" di Cagliari
  • Milano, Italy, 20162
    • Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia
  • Modena, Italy, 41100
    • Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia
  • Padova, Italy, 35122
    • Azienda Ospedialera Universitaria di Padova
  • Pisa, Italy, 54124
    • Azienda Ospedaliero-Universitaria Pisana
  • Roma, Italy, 00133
    • Fondazione Policlinico Tor-Vergata U.O.C.
  • Torino, Italy, 10126
    • Molinette Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Zutectra; Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.	Drug: Zutectra; Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.; Other Names: Human hepatitis B Immunoglobulin; HBIg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Trough levels of serum anti-HBs antibody concentrations	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number of adverse events will be documented including safety laboratory parameters reported as AEs.	24 weeks

Collaborators and Investigators

• Sponsor: Biotest
• Collaborators: AMS Advanced Medical Services GmbH
• Investigators: Principal Investigator: Didier Samuel, Professeur, Hospital Paul Brousse, Centre Hepato-Biliaire

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 15, 2013
• First Submitted That Met QC Criteria: May 15, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Liver transplantation; Prevention; Hepatitis B virus re-infection; HBV-DNA negative
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins
• Other Study ID Numbers: BT 987; 2012-002516-51 (EudraCT Number)