Chronic Hepatitis B MedDRA version: 19.0 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Tenofovir alafenamide (as hemifumarate)
Product Code: GS-7340
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tenofovir alafenamide (as hemi-fumarate)
Current Sponsor code:
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Males and non-pregnant, non-lactating females 2) Age at Baseline: 12 to 45 U/L (1.5 × ULN; 30 U/L) and = 10 × ULN (by central laboratory range) 8) Treatment-naïve (defined as =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Pregnant females, females 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. For a list of protocol-specified contraceptive methods, refer to Appendix 5. 3) Coinfection with HCV, HIV, or HDV 4) Evidence of hepatocellular carcinoma (screening alpha-fetoprotein [AFP] > 50 ng/mL or recent imaging study if AFP < 50 ng/mL) 5) Any history of, or current evidence 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) Currently receiving therapy with immunomodulators (e.g. corticosteroids), or immunosuppressants 9) Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator 10) Malignancy within the 5 years prior to screening. Subjects under evaluation for possible malignancy are not eligible. 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) Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days prior to the baseline visit. 14) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: -To evaluate the steady state pharmacokinetics (PK) of tenofovir alafenamide (TAF) and confirm the dose of TAF 25 mg tablet given once daily in treatment-naïve and treatment-experienced adolescent subjects (aged 12 to < 18 years) with chronic hepatitis B (CHB). Part B: To evaluate the safety, tolerability, and antiviral activity (HBV DNA < 20 IU/mL) of TAF 25 mg once daily versus placebo through Week 24 in treatment-naive and treatment-experienced adolescent subjects with CHB;Secondary Objective: -To evaluate for TAF 25 mg once daily versus placebo through Week 24 in treatment-naive and treatment-experienced adolescent subjects with CHB the following: 1) the serologic response (loss of HBeAg and seroconversion to anti-HBe, and loss of HBsAg and seroconversion to anti-HBs) 2)the biochemical (ALT normalisation) 3) the change in fibrosis as assessed by FibroTest 4) incidence of drug resistance mutations -To evaluate the palatability and acceptability of TAF 25 mg once daily in treatment-naïve and treatment-experienced adolescent subjects with CHB -To evaluate the open-label efficacy and safety of TAF 25 mg once daily from Week 24 to Week 240 in subjects initially randomized to TAF 25 mg once daily, and in subjects sequentially treated with placebo for 24 weeks and then switched to open-label TAF;Primary end point(s): The primary safety endpoints are: -Incidence of treatment-emergent serious adverse events (SAEs) and treatment-emergent adverse events at Week 24. The primary efficacy endpoint is: -The percentage of subjects with plasma HBV DNA < 20 IU/mL at Week 24;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Weeks 24, 48, 96, and 240;Secondary end point(s): The secondary safety endpoints are: -Graded laboratory abnormalities, Tanner stage assessment, selected bone and renal safety parameters, including percentage change in bone mineral density (BMD) of whole body minus head and lumbar spine by dual imaging x-ray absorptiometry (DXA), and change in serum creatinine, and eGFR by the Schwartz method to evaluate the safety and tolerability of the treatment regimen at Weeks 24, 48, 96, and 240. The secondary efficacy endpoints are: -The percentage of subjects with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240 -The proportion of subjects with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240 -The percentage of subjects with ALT normalization at Weeks 24, 48, 96, and 240 -The composite endpoint of ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240 -The change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240 -The percentage of subjects with HBeAg loss at Weeks 24, 48, 96, and 240, and the percentage of subjects with HBeAg seroconversion to anti-HBe at Weeks 24, 48, 96, and 240 (HBeAg-positive subjects only) -The composite endpoint of HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (HBeAg-positive subjects only) -The percentage of subjects with HBsAg loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240 - Incidence of resistance mutations at Weeks 24, 48, 96, and 240 - Acceptability/palatability of study drug at Baseline and Week 4, Week 24 , and at Week 36 | — |
Countries
Hong Kong, Korea, Republic of, Russian Federation, Taiwan, United States
Contacts
Public ContactClinical trials mailbox
Gilead Sciences International Ltd.
Outcome results
None listed