Ignite Creation Date:
2024-05-05 @ 12:07 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00255177
Status:
COMPLETED
Last Update Posted:
2009-11-03
First Post:
2005-11-15
Brief Title:
Antiviral Activity and Safety of 3 Different Doses of Mifepristone in Hepatitis C Infected Patients
Sponsor:
VGX Pharmaceuticals LLC
Organization:
VGX Pharmaceuticals LLC
Study Overview
Official Title:
A Randomized Open-label Phase II Trial of the Anti-HCV Activity and Safety of VGX-410 Mifepristone at 3 Dose Levels in HCV Infected Patients
Status:
COMPLETED
Status Verified Date:
2009-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hepatitis C virus HCV infects approximately 170 million people worldwide The current standard- of- care therapy of chronic HCV infection is a regimen of subcutaneously administered pegylated-interferon-α and ribavirin for 24 weeks for genotypes 2 and 3 to 48 weeks for genotype 1 The sustained viral response rates SVR in patients infected with genotypes 2 and 3 are 80 but remain 50 in patients infected with genotype 1 The treatment is quite toxic with approximately 30 of patients experiencing adverse events ie depression fever anemia fatigue requiring dose reduction or discontinuation of therapy This regimen is contraindicated in women who are pregnant and in patients with decompensated liver disease The absence of acceptable therapies for many patients with HCV infections makes new therapies desirable for this disease
Detailed Description:
The 341-nucleotide 5 non-translated region is the most conserved part of the hepatitis C virus HCV genome It contains a highly structured internal ribosomal entry site IRES that mediates cap-independent initiation of translation of the viral polyprotein by a mechanism that is unprecedented in eukaryotes The first step in translation initiation is assembly of eukaryotic initiation factor eIF 3 eIF2 GTP initiator tRNA and a 40S ribosomal subunit into a 43S preinitiation complex 1 2 The IRES contains sites that bind independently with the eIF3 and 40S ribosomal subunit components of 43S complexes and structural determinants that ensure the correct spatial orientation of these binding sites so that the 48S complex assembles precisely at the initiation codon Since inhibiting this early translation of viral protein should block HCV replication downstream this early critical step in replication is of great interest as a drug target All genotypes of HCV use the same pathway this drug target should be effective for all HCV genotypes
VGX-410 represents the first drug in a novel class of HCV IRES inhibitors under development VGX-410 is an orally active and bioavailable small-molecule organic drug Because a related formulation of mifepristone has been previously approved by the FDA for another indication medical abortion there are pre-existing data from animal toxicity tests showing the safety of this compound at very high doses 5 mgkg for 6 months in rats and macaques In addition chronic administration up to 200 mgday of this compound for the experimental treatment of a variety of malignant and non-malignant conditions has been well tolerated in non-HCV-infected subjects for up to 1 year 3-6
In cell culture tests VGX-410 has been shown to be effective in inhibiting HCV replication with the 50 and 90 effective antiviral concentrations EC50 and EC90 of 2 and 10 μM respectively Furthermore VGX-410 was shown to act synergistically with interferon-a IFN-a the most widely-used drug treatment option available today When used in combination with a low dose IFN-a at 1 IUml EC90 of VGX-410 was reduced to 3 µM Moreover since VGX-410 inhibits viral replication by blocking the cellular protein complex for HCV IRES there is reduced potential for viral mutation and resistance to this drug
From these in vitro data we would expect to observe 50 to 90 anti-HCV effects in humans at serum drug concentrations of 2 to 10 μM respectively Moreover we compiled the drug concentration results from several previously-reported clinical data on the level of steady-state concentrations in patients who took repeat daily doses of mifepristone 4 days For instance repeated oral administration of 100 and 200-mg mifepristone daily for 4 days achieved maximum plasma levels of 45 and 54 μM respectively 9
VGX-410 represents the first drug in a novel class of HCV IRES inhibitors under development VGX-410 is an orally active and bioavailable small-molecule organic drug Because a related formulation of mifepristone has been previously approved by the FDA for another indication medical abortion there are pre-existing data from animal toxicity tests showing the safety of this compound at very high doses 5 mgkg for 6 months in rats and macaques In addition chronic administration up to 200 mgday of this compound for the experimental treatment of a variety of malignant and non-malignant conditions has been well tolerated in non-HCV-infected subjects for up to 1 year 3-6
In cell culture tests VGX-410 has been shown to be effective in inhibiting HCV replication with the 50 and 90 effective antiviral concentrations EC50 and EC90 of 2 and 10 μM respectively Furthermore VGX-410 was shown to act synergistically with interferon-a IFN-a the most widely-used drug treatment option available today When used in combination with a low dose IFN-a at 1 IUml EC90 of VGX-410 was reduced to 3 µM Moreover since VGX-410 inhibits viral replication by blocking the cellular protein complex for HCV IRES there is reduced potential for viral mutation and resistance to this drug
From these in vitro data we would expect to observe 50 to 90 anti-HCV effects in humans at serum drug concentrations of 2 to 10 μM respectively Moreover we compiled the drug concentration results from several previously-reported clinical data on the level of steady-state concentrations in patients who took repeat daily doses of mifepristone 4 days For instance repeated oral administration of 100 and 200-mg mifepristone daily for 4 days achieved maximum plasma levels of 45 and 54 μM respectively 9
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| C Jo White MD | None | None | None |
| Viral Genomix Inc VGX | None | None | None |
| 450 Sentry Parkway | None | None | None |
| Blue Bell PA 19422 | None | None | None |