E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis B (CHB) Infection |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
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 |
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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:
•To evaluate the safety and tolerability of GS-9620 in subjects with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV)
•To evaluate the efficacy of GS-9620 at Week 24 measured by the change from Baseline (BL) in serum hepatitis B s antigen (HBsAg log10 IU/ml) levels |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To evaluate the rates of HBsAg loss and seroconversion at Weeks 24 and 48
• To evaluate the rates of hepatitis B e antigen (HBeAg) loss and seroconversion at Weeks 24 and 48
• To evaluate the change in log10 IU/ml serum HBsAg from Baseline to Weeks 4, 8, 12 and 48
• To evaluate the proportion of subjects with serum HBsAg decline ≥ 1 log10 IU/ml at Weeks 4, 8, 12, 24 and 48
• To evaluate the proportion of subjects experiencing hepatitis B virus (HBV) virological breakthrough
• To evaluate the incidence of drug resistance mutations |
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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 |
Pharmacogenomic (PG) Sub-study for Additional PG Analyses
All subjects will be eligible to participate in the pharmacogenomics (PG) sub-study. For subjects who provide separate consent for this optional genetic testing, an additional blood sample will be obtained. This sample is recommended to be collected at the Baseline/Day 1 visit, but may be collected at any time during the study or at a separate poststudy visit, if necessary. |
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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, 18–65 years of age inclusive
3. A negative serum pregnancy test is required for female subjects
4. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
5. Documented evidence of chronic HBV infection with detectable HBsAg levels at screening
6. Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below LLOQ 6 or more months prior to screening, and HBV DNA < 20 IU/ml at screening
7. Subjects currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
8. Willing to provide blood sample for TLR-7 and IL28B SNP assessment
9. Must be willing and able to comply with all study requirements |
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E.4 | Principal exclusion criteria |
1. Extensive bridging fibrosis or cirrhosis
3. Co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
4. Evidence of hepatocellular carcinoma
5. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection.
6. Significant cardiovascular, pulmonary, or neurological disease
7. Any of the conditions described in the protocol that may worsen in response to IFN
8. Chronic liver disease of a non-HBV etiology
9. Received solid organ or bone marrow transplant
10. Received prolonged therapy with immunomodulators or biologics within 3 months of screening
11. Use of another investigational agents within 3 months of screening, unless allowed by the Sponsor
12. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
13. Known hypersensitivity to study drug, metabolites or formulation excipients
14. Screening electrocardiogram (ECG) with clinically significant abnormalities and with QTcF interval ≥ 450 msec for males and ≥ 470 msec for females
15. Women who may wish to become pregnant during the course of the study
16. Male subjects unwilling to refrain from sperm donation for at least 90 days after the last dose of study drug
17. Use of any prohibited con-medications as described in the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is:
• The mean change in serum HBsAg (log10 IU/ml) from Baseline to Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks after cessation of therapy |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are:
• The proportion of subjects with HBeAg loss and seroconversion at Weeks 24 and 48
• The proportion of subjects with HBsAg loss and seroconversion at Weeks 24 and 48
• The mean change in log10 IU/ml serum HBsAg at Weeks 4, 8, 12 and 48
• The proportion of subjects with ≥ log10 decline in serum HBsAg titers from Baseline at Weeks 4, 8, 12, 24 and 48
• The proportion of subjects with breakthrough ( HBV DNA > 69 IU/ml with confirmation > 2 weeks after the initial test in the setting of satisfactory adherence to treatment with OAV)
• The proportion of subjects with drug resistance mutations at Week 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4, 8, 24 and 48 weeks after cessation of therapy |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 12 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Italy |
Korea, Republic of |
New Zealand |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |