Hepatitis B, Liver Transplantation
Conditions
Keywords
Hepatitis B, HBV, Orthotopic liver transplantation, Liver transplantation, Recurrence, Reinfection, Protective titers, HBsAb, Hepatitis B virus immune globulin, Niuliva
Brief summary
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.
Interventions
DRUGHepatitis B immune globulin
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.
Sponsors
Instituto Grifols, S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HBV Recurrence | First six and twelve months after liver transplantation | HBV recurrence is measured by seroconversion or reappearance of HBsAg and HBV DNA positivity |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerance | During and after each product administration (during the 12 month treatment period) | Safety and tolerance to the product administration will be measured by the detection of adverse events or clinically relevant changes in vital signs. |
Countries
Italy
Participant flow
Recruitment details
Fifteen subjects (newly liver transplanted due to HBV induced liver disease) were screened in the study, all received the study medication, and all completed the clinical study. First subject enrolled - 26 July 2010 Last subject completed - 16 June 2014
Participants by arm
| Arm | Count |
|---|---|
| Hepatitis B Immune Globulin Treatment group
Hepatitis B immune globulin: 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. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Hepatitis B Immune Globulin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Alcohol consumption - abstemious | 15 participants |
| Height | 170.33 centimeters STANDARD_DEVIATION 8.08 |
| Hepatitis history Has chronic HBV | 15 participants |
| Hepatitis history Has fulminant HBV | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment Italy | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
| Weight | 73.73 kilogram STANDARD_DEVIATION 12.05 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration)
Time frame: Days 3 to 7, Weeks 2 to 4, Months 2 to 6, and Months 7 to 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Day 3 | 764.7 IU/L | Standard Deviation 375.91 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Day 4 | 910.7 IU/L | Standard Deviation 282.39 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Day 5 | 969.6 IU/L | Standard Deviation 96.13 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Day 6 | 1000.0 IU/L | Standard Deviation 0 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Day 7 | 1000.0 IU/L | Standard Deviation 0 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Week 2 | 1073.6 IU/L | Standard Deviation 244.21 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Week 3 | 945.2 IU/L | Standard Deviation 250.38 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Week 4 | 1029.2 IU/L | Standard Deviation 175.21 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 2 | 592.5 IU/L | Standard Deviation 260.14 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 3 | 439.2 IU/L | Standard Deviation 218.22 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 4 | 398.1 IU/L | Standard Deviation 272.68 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 5 | 351.9 IU/L | Standard Deviation 179.01 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 6 | 369.0 IU/L | Standard Deviation 182.75 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 7 | 277.7 IU/L | Standard Deviation 89.14 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 8 | 304.3 IU/L | Standard Deviation 50.24 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 9 | 266.0 IU/L | Standard Deviation 34.7 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 10 | 301.0 IU/L | Standard Deviation 61.99 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 12 | 284.3 IU/L | Standard Deviation 137.47 |
| Hepatitis B Immune Globulin | HBsAb Pre-infusion Levels (Trough Levels Before Each Niuliva Administration) | Month 11 | 273.3 IU/L | Standard Deviation 117.93 |
Primary
HBV Recurrence
HBV recurrence is measured by seroconversion or reappearance of HBsAg and HBV DNA positivity
Time frame: First six and twelve months after liver transplantation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hepatitis B Immune Globulin | HBV Recurrence | Six Months | 0 participants |
| Hepatitis B Immune Globulin | HBV Recurrence | Twelve Months | 0 participants |
Secondary
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.
Time frame: During and after each product administration (during the 12 month treatment period)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hepatitis B Immune Globulin | Safety and Tolerance | 15 participants |