Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant

NCT00507689 | Completed Phase 2 Results

• 1 other identifier: GS-US-203-0107
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

The objective of this 96-week study was to evaluate the safety and antiviral efficacy of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, coformulated; Truvada®) with or without hepatitis B immunoglobulin (HBIg) in preventing the recurrence of chronic hepatitis B following liver transplantation, in participants who were chronically infected with hepatitis B prior to transplantation. Prior to enrollment, participants were required to have received at least 12 weeks of HBIg therapy following liver transplantation. Enrolled participants then received FTC/TDF plus HBIg for an initial 24-week pre-randomization treatment period. Participants who completed the pre-randomization period and who achieved sustained viral suppression were randomized to continue treatment with FTC/TDF with or without HBIg for an additional 72 weeks (randomized period). The antiviral efficacy of treatment was assessed by measuring hepatitis B virus levels in the blood (HBV DNA). Safety and tolerability was monitored by assessing adverse events and various laboratory parameters.

Conditions

Chronic Hepatitis B

Keywords

Truvada; HBIg; Chronic Hepatitis B Recurrence; Post Orthotopic Liver Transplant

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With HBV Recurrence Prior to or at Week 72

  HBV recurrence was defined as either HBV DNA ≥ 400 at 2 consecutive visits before Week 72, or HBV DNA ≥ 400 at the Week 72 visit.

  Pretreatment baseline through Week 72

Secondary Outcomes (5)

• Percentage of Participants With HBV Recurrence at Week 96

  Week 96

• Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72

  Week 72

• Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96

  Week 96

• Percentage of Participants With Normal ALT at Week 72

  Week 72

• Percentage of Participants With Normal ALT at Week 96

  Week 96

Study Arms (2)

FTC/TDF+HBIg

EXPERIMENTAL

Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF+HBIg in the randomized period.

Drug: FTC/TDF; Drug: Hepatitis B Immunoglobulin (HBIg)

FTC/TDF

EXPERIMENTAL

Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF in the randomized period.

Drug: FTC/TDF

Interventions

FTC/TDF DRUG

Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.

Also known as: Truvada

FTC/TDF; FTC/TDF+HBIg

Hepatitis B Immunoglobulin (HBIg) DRUG

HBIg was administered either intravenously or by intramuscular injection at a dose and frequency as prescribed by the investigative site protocol.

FTC/TDF+HBIg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects (18-75 years of age) with either hepatitis e antigen (HBeAg) positive or HBeAg negative chronic HBV prior to transplant
• Willing and able to provide written informed consent
• Subjects with detectable antibody to hepatitis B surface antigen performed by a local laboratory result within 30 days of screening
• Subjects must have been stable and may not have had 2 or more of the following laboratory parameters associated with decompensated liver disease: conjugated bilirubin \> 1.5 x the upper limit of the normal range (ULN), prothrombin time \> 1.5 x ULN, platelets \< 60,000/mm\^3, serum albumin \< 3.0 g/dL
• Must have had at least 12 weeks of center-specific prophylactic therapy including hepatitis B immunoglobulin (HBIg) posttransplant
• Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation
• No significant evidence of ongoing deterioration of renal function
• Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)

You may not qualify if:

• Subjects with HBV recurrence, ie, confirmed HBV DNA ≥ 400 copies/mL, following liver transplant
• Pregnant women, women who were breast feeding or who believed they may have wished to become pregnant during the course of the study
• Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study and for at least 30 days from the date of last dose of study drug
• Evidence of hepatocellular carcinoma (HCC), eg, alpha-fetoprotein \> 50 ng/mL, or by any other standard of care measure or presence of multifocal HCC at the time of transplantation if transplantation was within 144 weeks of screening
• Prior TDF or FTC/TDF experience post-transplant or \> 12 months treatment with TDF or FTC/TDF treatment pretransplant
• Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus pretransplant or at screening
• Significant renal, cardiovascular, pulmonary, or neurological disease
• Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
• Were likely to receive systemic drugs with nephrotoxic potential, except immunosuppressive agents (eg, cyclosporine, tacrolimus), during the course of the study
• History of variceal bleeding or hepatic encephalopathy following orthotopic liver transplantation

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

Unknown Facility

Los Angeles, California, 90048, United States

Location

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Chicago, Illinois, 60608, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; hepatitis B hyperimmune globulin

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Lewis Teperman, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 26, 2007
• Study Start: September 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: March 14, 2014
• Results First Posted: September 19, 2013

Record last verified: 2014-02

Locations

US (7)