- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00507689
Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant
A Phase 2, Open-Label Randomized Study to Evaluate the Efficacy and Safety of the Combination Product, Emtricitabine/Tenofovir Disoproxil Fumarate in the Presence or Absence of Hepatitis B Immunoglobulin (HBIg) in Preventing Recurrence of Chronic Hepatitis B (CHB) Post-Orthotopic Liver Transplant (OLT)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90048
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San Francisco, California, United States, 94115
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San Francisco, California, United States, 94143
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Georgia
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Atlanta, Georgia, United States, 30322
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Illinois
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Chicago, Illinois, United States, 60608
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New York
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New York, New York, United States, 10016
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New York, New York, United States, 10029
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: FTC/TDF+HBIg
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.
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Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
Other Names:
HBIg was administered either intravenously or by intramuscular injection at a dose and frequency as prescribed by the investigative site protocol.
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Experimental: FTC/TDF
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.
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Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With HBV Recurrence Prior to or at Week 72
Time Frame: Pretreatment baseline through Week 72
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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.
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Pretreatment baseline through Week 72
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With HBV Recurrence at Week 96
Time Frame: Week 96
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HBV recurrence was defined as HBV DNA ≥ 400 at the Week 96 visit.
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Week 96
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Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72
Time Frame: Week 72
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Week 72
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Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96
Time Frame: Week 96
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Week 96
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Percentage of Participants With Normal ALT at Week 72
Time Frame: Week 72
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Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69.
Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.
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Week 72
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Percentage of Participants With Normal ALT at Week 96
Time Frame: Week 96
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Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69.
Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.
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Week 96
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lewis Teperman, MD, NYU Langone Health
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Disease Attributes
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Recurrence
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
- Immunoglobulins
- Immunoglobulins, Intravenous
Other Study ID Numbers
- GS-US-203-0107
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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