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

Study Overview
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Brief Summary
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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).

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

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Zutectra


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zutectra<br>Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week. | Drug: Zutectra<br>* Subcutaneous injections of Zutectra up to 1,000 IU (2 ml) per week.<br>* Other names: HBIg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention, Hepatitis B virus re-infection, HBV-DNA negative, Liver transplantation