Clinical trial NCT01856413: A Clinical Trial of Zutectra in Patients Who Recently Received a Liver Transplant
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B
Keywords: Prevention
Hepatitis B virus re-infection
HBV-DNA negative
Liver transplantation
Lead sponsor: Biotest
Sponsor class: INDUSTRY
Collaborators: name: AMS Advanced Medical Services GmbH
First posted: 2013-05-17
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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).


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

Primary outcomes:
measure: Trough levels of serum anti-HBs antibody concentrations
timeFrame: 24 weeks
Secondary outcomes:
measure: Hepatitis B related re-infections
timeFrame: 24 weeks
Other outcomes:
measure: Adverse Events
timeFrame: 24 weeks
Locations:
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Bari
country: Italy
facility: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
city: Bologna
country: Italy
facility: S. Orsola Hospital
city: Cagliari
country: Italy
facility: Azienda ospedaliera "G. Brutzu" di Cagliari
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia
city: Modena
country: Italy
facility: Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia
city: Padova
country: Italy
facility: Azienda Ospedialera Universitaria di Padova
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: Fondazione Policlinico Tor-Vergata U.O.C.
city: Torino
country: Italy
facility: Molinette Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: Hospital Paul Brousse, Centre Hepato-Biliaire
name: Didier Samuel, Professeur
role: PRINCIPAL_INVESTIGATOR
References: