| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of Subjects with Chronic Hepatitis B and who are currently not on Treatment |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 19.0 |
| 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 |
|
| 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 |
- To evaluate the safety and tolerability of GS-9620 in adult subjects with chronic hepatitis B (CHB) infection who are currently not being treated
-To evaluate the efficacy of GS-9620 as measured by the change from Baseline (BL) to Week 24 in serum Hepatitis B surface Antigen (HBsAg log10 IU/mL) levels |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the proportions of subjects with HBeAg loss and seroconversion at Weeks 24 and 48
- To evaluate the proportions of subjects with HBsAg loss and seroconversion at Weeks 24 and 48
- To evaluate the change in serum HBsAg log10 IU/mL from Baseline (BL) at Weeks 12 and 48
- To evaluate the proportions of subjects with a ≥ 0.5 log10 IU/mL decline in HBsAg at Weeks 12, 24, and 48
- To evaluate the proportions of subjects with HBV DNA <LLOQ at Weeks 24 and 48
- To evaluate the proportion of subjects experiencing virologic breakthrough
- To evaluate the incidence of drug resistance mutations through Week 48
- To evaluate the pharmacokinetics (PK) of GS-9620 |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic (PK) Substudy
All subjects who are willing to consent will be eligible to participate in the optional intensive PK substudy. The PK substudy may occur at the Week 11 visit.
Sample for Optional Genomic Research
All subjects who are willing to consent will be eligible to participate in Optional Genomic Research. If consent is given, an additional
blood sample should be drawn at the Baseline/Day 1 visit. If sample is not obtained at Baseline/Day 1 visit, it may be drawn at any time
during the study. The sample will be stored for possible future genomics analyses. |
|
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible to participate in the study:
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 or non-pregnant female subjects, 18-65 years of age inclusive based on the date of the screening visit
3 Documented evidence of chronic HBV infection (e.g., documented HBsAg positive for more than 6 months)
4 Screening HBV DNA ≥ 2000 IU/mL
5 Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
6 Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to randomization.
7 Willing to provide blood sample for TLR-7 and IL28B SNP assessment
8 Must be willing and able to comply with all study requirements |
|
| E.4 | Principal exclusion criteria |
1 Extensive bridging fibrosis or cirrhosis as defined clinically
2 Received oral antiviral (OAV) treatment for HBV within 3 months of screening
3 Received prolonged therapy with immune-modulators or biologics within 3 months of screening
4 Subjects meeting any of the following laboratory parameters at screening:
a) White blood cell count < 2500 cell/mm
b) Neutrophil count < 1500 cell/mm3 (or < 1000 cell/mm3 if considered a physiological variant in a subject of African descent)
c) ALT > 5x the upper limit of normal (ULN)
d) INR >ULN unless the subject is stable on anticoagulant regimen affecting INR
e) Albumin <3.9 g/dL
f) Total bilirubin >2 mg/dL
g) Platelet count <125,000 /mL
h) Estimate creatinine clearance (CLcr) <50 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation
5 Co-infection with HCV, HIV or HDV
6 Evidence of hepatocellular carcinoma (e.g., as evidenced by recent imaging)
7 Any malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection. Subjects under evaluation for possible malignancy are not eligible
8 Significant cardiovascular, pulmonary, or neurological disease
9 Any of the following conditions that may worsen in response to IFN
10 Chronic liver disease of a non-HBV etiology
11 Received solid organ or bone marrow transplant
12 Use of investigational agents within 3 months of screening, unless allowed by the Sponsor
13 Use of any prohibited concomitant medications as described in protocol
14 Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
15 Screening electrocardiogram (ECG) with clinically significant abnormalities, including QTcF interval (QT corrected using Fridericia’s formula) ≥ 450 msec for males and ≥ 470 msec for females
16 Known hypersensitivity to study drugs, metabolites or formulation excipients
17 Lactating or pregnant females or those who may wish to become pregnant during the course of the study
18 Male subjects unwilling to refrain from sperm donation, or those intending to father a child, for at least 90 days after the last dose of GS-9620/ Placebo and for at least 30 days after the lost dose of TDF
19 Believed by the Principal Investigator to be inappropriate for study participation for any reason |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the mean change (measured in log10 IU/mL) in serum HBsAg from Baseline to Week 24.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline to Week 24.
- Screening Visit
- Treatment Period Visits: Baseline/Day 1, Baseline + 7 hours, Weeks 2, 4, 8, 10, 11, 11 +24 hours (24 hours after 12th dose), 12, 16, 24, 36, and 48 |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
- Proportions of subjects with HBeAg loss and seroconversion at Weeks 24 and 48
- Proportions of subjects with HBsAg loss and seroconversion at Weeks 24 and 48
- The mean change (measured in log10 IU/mL) in serum HBsAg at Weeks 12 and 48
- Proportions of subjects with a ≥ 0.5 log10 IU/mL decline in serum HBsAg titers from Baseline at Weeks 12, 24 and 48
- Proportions of subjects with HBV DNA <LLOQ at Weeks 24 and 48
- Proportion of subjects experiencing virologic breakthrough (defined as confirmed HBV DNA ≥ 69 IU/mL after having been <69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir)
- Proportion of subjects with drug resistance mutations through Week 48 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Screening Visit
- Treatment Period Visits: Baseline/Day 1, Baseline + 7 hours, Weeks 2, 4, 8, 10, 11, 11 +24 hours (24 hours after 12th dose), 12, 16, 24, 36, and 48
- Optional Treatment Extension Phase Visits: Weeks 60, 72, 96, 120, and 144 |
|
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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, Democratic People's Republic of |
| New Zealand |
| Romania |
| Taiwan |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
Print
