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

Hepatitis B Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01856413
• Other study ID #: BT 987
• Secondary ID: 2012-002516-51
• Status: Completed
• Phase: Phase 3
• First received: May 15, 2013
• Last updated: March 24, 2015
• Start date: December 2012
• Est. completion date: September 2014

Study information

• Verified date: March 2015
• Source: Biotest
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Agence Nationale de Sécurité du Médicament et des produits de santéItaly: Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B

Intervention

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

Locations

Country	Name	City	State
France	Hopital de la Croix Rousse	Lyon
France	Hôpital Paul Brousse	Villejuif
Italy	Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari	Bari
Italy	S. Orsola Hospital	Bologna
Italy	Azienda ospedaliera "G. Brutzu" di Cagliari	Cagliari
Italy	Azienda Ospedaliera Ospedale Niguarda Ca Granda-Chirurgia	Milano
Italy	Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia	Modena
Italy	Azienda Ospedialera Universitaria di Padova	Padova
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Tor-Vergata U.O.C.	Roma
Italy	Molinette Hospital	Torino
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
United Kingdom	University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham
United Kingdom	King's College Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Biotest	AMS Advanced Medical Services GmbH

Countries where clinical trial is conducted

France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events	The number of adverse events will be documented including safety laboratory parameters reported as AEs.	24 weeks	Yes
Primary	Trough levels of serum anti-HBs antibody concentrations		24 weeks	No
Secondary	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	No