Clinical trial NCT00895713: Efficacy and Safety of Intramuscular HBIG Grifols for the Prevention of Recurrence After Liver Transplantation
Official title: Efficacy and Safety of Intramuscular Hepatitis B Virus Immune Globulin Grifols for the Prevention of Hepatitis B Virus Recurrence After Orthotopic Liver Transplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Keywords: Hepatitis B
HBV
Anti-hepatitis B antibodies
Immunoglobulins
liver transplantation
Protective levels
Recurrence
Intramuscular
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
First posted: 2009-05-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if treatment with intramuscular hepatitis B virus immune globulin Grifols, a new specific hepatitis B immune globulin, is effective and safe for the prevention of hepatitis B virus recurrence after orthotopic liver transplantation.


Eligibility criteria: Inclusion Criteria:

1. Male or female.
2. Age \> 18 years and \< 70 years.
3. OLT recipient for HBV infection-related disease for \> 18 months before inclusion in the clinical trial.
4. Serum HBsAg-positive within 3 months before transplantation.
5. Serum HBsAg-negative just before inclusion in the clinical trial.
6. Serum HbeAg-negative just before inclusion in the clinical trial.
7. Serum HBV DNA-negative by DNA PCR-amplification assay (lower detection limit 102 genomes/ml) just before inclusion in the clinical trial.
8. Continuous and interrupted prophylaxis with HBIG after an-hepatic phase as part of the subject clinical care.
9. Trough serum HBsAg Ab (HBsAg IgG) titer (immediately pre-dose) \> 150 I.U./l in at least 2 consecutive determinations within last 3 months before inclusion in the clinical trail.
10. Signed informed consent.

Exclusion Criteria:

1. Serum HBsAg-positive just before inclusion in the clinical trial.
2. Serum HBeAg-positive within 3 months before transplantation.
3. Serum HBV DNA-positive by standard DNA hybridisation assay (lower detection limit 105 genomes/ml), or by any less sensitivity technique, within 3 months before transplantation.
4. Unknown serum HBV replication status (no data about HbeAg and HBV DNA) within 3 months before transplantation.
5. Previous recurrence of HBV in the transplanted liver defined by serum HBV DNA- positive by sensitive hybridisation (lower detection limit 105 genomes/ml) assay or any less sensitive technique, and/or serum HBeAg-positive, and/or serum HBsAg-positive.
6. Re-transplanted liver even for reasons not related to HBV infection.
7. Evidence of hepatocellular carcinoma in the transplanted liver, or metastatic disease, at time of inclusion in the clinical trial.
8. Evidence of graft rejection at time of inclusion in the clinical trial.
9. Life-expectancy less than 1 year.
10. VHC infection.
11. HIV type 1 or type 2 infection.
12. Acute HAV infection.
13. Previous treatment with i.m. HBIG Grifols within 3 months before inclusion in the clinical trial.
14. Intolerance or allergy to any i.m. HBIG Grifols containing substance (glycine, sodium chloride, sterile water for injection, homologous human immune globulin).
15. History of SAEs related to the administration of human blood-derived products.
16. History of frequent AEs, even non-serious, related to the administration of human blood-derived products.
17. Selective IgA deficiency with Abs against IgA.
18. Platelet count \< 50 x 109/L.
19. Prothrombin time (PT) \< 60%.
20. Activated partial thromboplastin time (APTT) ratio \> 1.5.
21. Any haemostatic abnormality contraindicating i.m. injection according to investigator's judgement.
22. Haemoglobin \< 11 g/dl.
23. Alcohol or drug abuse at the moment or within 1 year before inclusion in the clinical trial.
24. Pregnant woman or woman who is expecting to be pregnant within 1 year after inclusion in the clinical trial.
25. Breast-feeding woman.
26. Any severe acute or chronic medical, surgical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, makes the subject inappropriate for entry in this clinical trial.
27. Impossibility to donate a serum sample before the first investigational product administration.
28. Planned treatment with Ig other than i.m. HBIG Grifols within the clinical trial period.
29. Planned modification, during the clinical trial period, of the prophylactic regimen with nucleoside analogues followed by the subjects, if any, within last 3 months before inclusion in the clinical trial.
30. The subject has been previously admitted to this clinical trial.
31. Participation in other clinical trial within 3 months before study inclusion.
32. Subject's incapacity of giving consent personally.

Primary outcomes:
measure: Mean trough serum HBsAg Ab titer
timeFrame: Months 4-6
Secondary outcomes:
measure: HBV recurrence percentage in long-term OLT recipients during i.m. HBIG Grifols treatment period
timeFrame: Week 2 - 7 months
measure: Mean trough HBsAg Ab titer
timeFrame: 4 months
measure: Individualised trough HBsAg Ab titer
timeFrame: Week 2 - 7 months
measure: Number of subjects with serum HBV DNA-positive samples by DNA PCR-amplification assay
timeFrame: Week 2 - 7 months
measure: Safety and tolerability
timeFrame: 7 months
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: Cisanello Hospital. (University of Pisa).
city: Torino
country: Italy
facility: Ospedaliera Molinette
Study officials:
affiliation: Liver Transplantation Co-ordinating Section. Cisanello Hospital. (University of Pisa).
name: Franco Filipponi, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: