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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biotest
ClinicalTrials.gov Identifier:
NCT01856413
First received: May 15, 2013
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

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.

Sixty 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).


Condition Intervention Phase
Hepatitis B
Drug: Zutectra
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Biotest:

Primary Outcome Measures:
  • Trough levels of serum anti-HBs antibody concentrations [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hepatitis B related re-infections [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Adverse Events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    The number of adverse events will be documented including safety laboratory parameters reported as AEs.


Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01856413

Locations
France
Hopital de la Croix Rousse
Lyon, France, 69004
Hôpital Paul Brousse
Villejuif, France, 94804
Italy
S. Orsola Hospital
Bologna, Italy, 40139
Ospedale Brotzu
Cagliari, Italy, CA 09135
Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia
Modena, Italy, 41100
Azienda Ospedialera di Padova
Padova, Italy, 35122
Molinette Hospital
Torino, Italy, 10126
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital 12 de Octubre
Madrid, Spain, 28041
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
United Kingdom
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
King's College Hospital
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Biotest
Investigators
Principal Investigator: Didier Samuel, Professeur Hospital Paul Brousse, Centre Hepato-Biliaire
  More Information

No publications provided

Responsible Party: Biotest
ClinicalTrials.gov Identifier: NCT01856413     History of Changes
Other Study ID Numbers: BT 987, 2012-002516-51
Study First Received: May 15, 2013
Last Updated: May 26, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Biotest:
Prevention
Hepatitis B virus re-infection
HBV-DNA negative
Liver transplantation

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Immunoglobulins
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014