Efficacy and Safety of Niuliva® for the Prevention of Hepatitis B Virus Recurrence in Newly Orthotopic Liver Transplant Recipients

Study Overview
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Brief Summary
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The aim of this clinical trial is to evaluate the efficacy, safety, and tolerability of Niuliva (Hepatitis B virus immune globulin) in the prophylaxis of hepatitis B virus (HBV) reinfection in patients submitted to liver transplantation due to HBV-induced liver disease by reaching and maintaining certain hepatitis B antibody (HBsAg) levels considered as protective during the first six and twelve months post-transplantation.

Official Title
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Efficacy and Safety of Niuliva® for the Prevention of Hepatitis B Virus Recurrence in Newly Orthotopic Liver Transplant Recipients.

Conditions
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Hepatitis B, Liver Transplantation

Intervention / Treatment
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* Drug: Hepatitis B immune globulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. Patients from 18 to 70 years of age (both included). Serum HBV DNA-negative determined by DNA PCR-amplification assay just prior to anhepatic phase visit. Serum HBeAg negative just prior to anhepatic phase visit. Patients who are to undergo liver transplantation due to liver disease associated to HBV. The patient agrees to participate and comply with all the aspects of the protocol, including blood sampling, for the total duration of the study. Signed informed consent. Exclusion Criteria: Patients who have already experienced a liver transplantation even for reasons not related to HBV infection. Patients with unknown serum HBV replication status (data on HBeAg and HBV DNA). Patients with known allergies to any component of Niuliva®. History of serious adverse events (SAEs) or frequent adverse events (AEs) related to the administration of human blood-derived products. Patient with unknown viral status for HCV, HAV, HIV type 1 and type 2 Patients with selective IgA deficiency. Any haemostatic abnormality contraindicating i.v. injection according to the investigator's judgment. Patient suffers from any acute or chronic medical, surgical or psychiatric condition or laboratory abnormality that may increase the risk associated with the study participation or investigational product administration, or may interfere with the interpretation of the study results. Known abuse of alcohol, drugs or other chemical substances; or has done so in the past 6 months. Breast-feeding women or pregnant women at the time of inclusion or who are expecting to be pregnant within the next 7 months after inclusion. Subject has participated in any other investigational study within the last 3 months. Existing possibility that the patient may be treated with other products containing specific anti-hepatitis B immunoglobins (other than Niuliva®) in a period of 13 months. Subject is incapable of giving consent personally.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Hepatitis B immune globulin<br>Treatment group (newly liver transplanted subjects due to HBV induced liver disease) | Drug: Hepatitis B immune globulin<br>* Daily doses of 10,000 IU of intravenous hepatitis B immune globulin during the first week post-transplantation (anhepatic phase + days 1-7), followed by weekly and monthly doses of 5,000 IU during weeks 2,3, and 4 and months 2,3,4,5,6,7,8,9,10,11 and 12, respectively.<br>* Other names: Niuliva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV Recurrence | HBV recurrence is measured by seroconversion or reappearance of HBsAg and HBV DNA positivity | First six and twelve months after liver transplantation | 
| HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) |  | Days 3 to 7, Weeks 2 to 4, Months 2 to 6, and Months 7 to 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerance | Safety and tolerance to the product administration will be measured by the detection of adverse events or clinically relevant changes in vital signs. | During and after each product administration (during the 12 month treatment period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV, Hepatitis B, Orthotopic liver transplantation, Liver transplantation, Recurrence, Reinfection, Protective titers, HBsAb, Hepatitis B virus immune globulin, Niuliva