E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Long term infection with hepatitis B virus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are as follows: -To evaluate the efficacy of switching to TAF 25 mg QD versus continued TDF 300 mg QD in virologically suppressed subjects with chronic HBV as determined by the proportion of subjects with HBV DNA ≥ 20 IU/mL (as defined by the modified US FDA-defined snapshot algorithm) at Week 48 -To compare the safety and tolerability of switching to TAF 25 mg QD versus continuing TDF 300 mg QD in virologically suppressed subjects with chronic HBV at Week 48 |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives of this study are as follows: -To compare the safety of switching to TAF 25 mg QD versus continued TDF 300 mg QD as determined by the percent change from baseline in hip and spine Bone Mineral Density at Week 48 -To compare the safety of switching to TAF 25 mg QD versus continued TDF 300 mg QD as determined by the change from baseline in estimated creatinine clearance by Cockcroft-Gault method at Week 48 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures 2)Adult male and non-pregnant, non-lactating female subjects, ≥18 years of age based on the date of the screening visit. A negative serum pregnancy test at Screening is required for female subjects of childbearing potential 3) Documented evidence of chronic HBV infection previously (e.g., documented HBsAg positive for more than 6 months) 4) Maintained on TDF 300 mg QD for at least 48 weeks, and as monotherapy for CHB for at least 24 weeks prior to screening and with viral suppression (HBV DNA < LLOQ by local laboratory assessment) for a minimum of 12 weeks prior to Screening, and including a Screening HBV DNA value of < 20 IU/mL (by central laboratory). The assay that will be used to quantify HBV DNA in Study GS-US-320-4018 is the Roche COBAS Ampliprep-COBAS TaqMan Hepatitis B Test v2.0 5) Estimated creatinine clearance ≥ 50 ml/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the Screening evaluation 6) Normal ECG (or if abnormal, determined by the Investigator not to be clinically significant) 7) Must be willing and able to comply with all study requirements |
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E.4 | Principal exclusion criteria |
1) Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study 2) Males and females of reproductive potential who are unwilling to use an “effective”, protocol-specified method(s) of contraception during the study. 3) Co-infection with HCV, HDV, HIV -Subjects who are HCV positive, but have a documented negative HCV RNA, are eligible 4)Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging) 5) Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage) 6) Abnormal hematological and biochemical parameters 7) Received solid organ or bone marrow transplant 8) Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the investigator 9) Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (e.g. basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible. 10) Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion 11) Known hypersensitivity to study drugs, metabolites, or formulation excipients 12) Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance 13) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements. 14) Use of investigational agents within 3 months of Screening, unless allowed by the Sponsor 15) Use of any prohibited medications. Subjects on prohibited medications, who are otherwise eligible, will need a wash out period of at least 30 days prior to the Baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is: -Proportion of subjects with HBV DNA ≥ 20 IU/mL (as determined by the modified US FDA-defined snapshot algorithm) at Week 48 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are: -Proportion of subjects with HBV DNA ≥ 20 IU/mL (as determined by the modified US FDA-defined snapshot algorithm) at Week 96 -Proportion of subjects with serological response (loss of Hepatitis B s antigen [HBsAg] and seroconversion to anti-HBs, and loss of Hepatitis B e antigen [HBeAg] and seroconversion to anti-HBe in HBeAg-positive subjects) at Weeks 48 and 96 -Proportion of subjects with biochemical response (normal ALT and normalized ALT) at Weeks 48 and 96 -Change from baseline in fibrosis as assessed by FibroTest® at Weeks 48 and 96 -Proportion of subjects with HBV DNA < 20 IU/mL and target detected/not detected (i.e. < LLOD) at Weeks 48 and 96 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Hong Kong |
Italy |
Korea, Republic of |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Study is defined as when the last subject has completed 96 weeks of treatment, or when the last subject has completed 96 weeks of treatment and up to 24 weeks of treatment free follow-up if appropriate, alternative anti-HBV treatment is not initiated after completing 96 weeks of study treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |