本帖最后由 StephenW 于 2013-12-2 16:07 编辑
Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B This study is currently recruiting participants.
Verified November 2013 by Gilead Sciences
Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01943799
First received: September 12, 2013
Last updated: November 14, 2013
Last verified: November 2013
 Purpose This is a randomized, open-label, multicenter Phase 2 study to evaluate the safety and efficacy of GS-4774 in subjects with chronic hepatitis B (CHB) viral infection who have been virally suppressed with an oral antiviral medication. One hundred and seventy-five subjects will be randomized in a 1:2:2:2 ratio to the treatment arms for 20 weeks.
| Study Type: | Interventional | | Study Design: | Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment | | Official Title: | A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B |
Resource links provided by NLM:
MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B
Drug Information available for: Recombinant Hepatitis B vaccine Hepatitis A Vaccines
U.S. FDA Resources
Further study details as provided by Gilead Sciences:
Primary Outcome Measures: - Mean change in log10 IU/mL serum hepatitis B surface antigen (HBsAg) from Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
Secondary Outcome Measures: - Mean change in log10 IU/mL serum HBsAg from Baseline to Weeks 12 and 48 [ Time Frame: Baseline to Weeks 12 and 48 ] [ Designated as safety issue: No ]
- Proportion of participants with HBsAg loss and HBsAg seroconversion at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
- Proportion of participants with hepatitis B e antigen (HBeAg) loss and HBeAg seroconversion at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
- Proportion of participants with a 1-log decline in HBsAg at Weeks 12, 24, and 48 [ Time Frame: Weeks 12, 24, and 48 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 175 | | Study Start Date: | September 2013 | | Estimated Study Completion Date: | March 2015 | | Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions | Experimental: OAV AloneParticipants will continue their prebaseline OAV treatment alone from baseline to Week 48.
| Drug: OAV RegimenOral antiviral (OAV) regimen as administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
| Experimental: OAV + GS-4774 2 YUParticipants will continue their prebaseline OAV from baseline to Week 48, and will receive GS-4774 2 yeast units (YU) from baseline to Week 20.
| Biological: GS-4774GS-4774 2, 10, or 40 YU administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV RegimenOral antiviral (OAV) regimen as administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
| Experimental: OAV + GS-4774 10 YUParticipants will continue their prebaseline OAV from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.
| Biological: GS-4774GS-4774 2, 10, or 40 YU administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV RegimenOral antiviral (OAV) regimen as administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
| Experimental: OAV + GS-4774 40 YUParticipants will continue their prebaseline OAV from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.
| Biological: GS-4774GS-4774 2, 10, or 40 YU administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Drug: OAV RegimenOral antiviral (OAV) regimen as administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
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Eligibility
| Ages Eligible for Study: | 18 Years to 65 Years | | Genders Eligible for Study: | Both | | Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria: - Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- Currently taking an HBV oral antiviral medication
- Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months)
- Virally-suppressed (HBV DNA below the lower limit of quantification [LLOQ] by for ≥ 1 year)
Exclusion Criteria: - Cirrhosis
- Inadequate liver function
- Co-infection with hepatitic C virus (HCV), HIV or hepatitic D virus (HDV)
- Evidence of hepatocellular carcinoma
- Significant cardiovascular, pulmonary, or neurological disease
- Females who are pregnant or may wish to become pregnant during the study
- Received solid organ or bone marrow transplant
- Use of another investigational agents within 3 months of screening
- Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
- History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease ulcerative colitis, autoimmune disease
- Known hypersensitivity to study drug, metabolites or formulation excipients
- Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Participants under evaluation for possible malignancy are not eligible.
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发表于 2013-12-2 16:06
，没听说过啊，只听说过GS9620 ，arc-520，rep 9ac,这是什么类型的药物？
As shown in the graphic to the right, administration of Tarmogens initially results in binding of the yeast to white blood cells called antigen-presenting cells, the most important of which are known as dendritic cells, near the injection site. The dendritic cells are activated as a result of the Tarmogens binding to molecules called Toll-like receptors and other receptor molecules on the surface of the dendritic cell, resulting in the activation of immune signaling molecules called cytokines. The dendritic cell then engulfs the Tarmogen. Multiple Tarmogens may be taken up by the same dendritic cell.
The Tarmogen is processed by the dendritic cell in two ways. First, the Tarmogen is engulfed by subcellular bodies known as endosomes and the protein inside the endosome is cut into shorter fragments called peptides. These peptides are presented by Class II MHC molecules on the surface of the dendritic cell. In combination with IL-12, a cytokine that is produced by the dendritic cell, these MHC-peptide complexes on the surface of the dendritic cell are recognized by and activate cells involved in viral immunity called CD4+ helper T cells.
Dendritic cells also process Tarmogens by engulfing them with different subcellular bodies called phagosomes. This results in presentation of peptides, including the antigen from inside the Tarmogen, to cells, known as CD8+ killer T cells, via Class I MHC molecules on the surface of the dendritic cell, resulting in proliferation of identical antigen specific CD8+ T cells. CD4+ helper T cells are so named because one of their roles is to “help” activate killer T cells by expressing a cytokine called interferon gamma, IFNγ.
The newly activated CD8+ killer T cells move throughout the body and identify any other cell that expresses the same disease protein as the one recognized by the CD8+ killer T cells. Once the CD8+ killer T cell finds another cell in the body containing the target protein, it can kill the cell using multiple mechanisms.
