Hepatitis C Virus InfectionPhase 2NCT00255177
Antiviral Activity and Safety of 3 Different Doses of Mifepristone in Hepatitis C Infected Patients
A Phase 2 study testing VGX-410 (Mifepristone) in people with Hepatitis C Virus Infection, run by VGX Pharmaceuticals, LLC at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C Virus Infection
- What is being tested?
- VGX-410 (Mifepristone)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2005to Jan 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Hepatitis C infection for ≥ 1 year. Viral load at entry will be measured by the Amplicor Hepatitis C Virus Test Version 2.0 (Roche Molecular Systems; Plesasanton, CA) and genotyped by Trugene HCV 5'NC Genotyping kit (Visible Genetics; Toronto, Canada) performed within 90 days prior to study entry by a lab(s) certified for the assays.
- Male or female ages 18-65 years, inclusive.
- Plasma hepatitis C RNA of >105 copies/mL (or equivalent international units)
- Laboratory values: stable hepatic, renal, and hematological indices obtained within 30 days prior to study entry, as follows:
- Absolute neutrophil count (ANC) >= 750/mm³
- Hemoglobin >= 10.0 g/dL
Show all 25Show fewer
- Platelet count >= 100,000/mm3
- Creatinine <= 2 x ULN
- AST (SGOT), ALT (SGPT), and alkaline phosphatase <= 3 x ULN
- Total bilirubin <= 3 x ULN
- Albumin >= 3 g/dL
- Normal PT and PTT
- Serum lipase <= 1.5 x ULN
- TSH within normal limits (0.5-6.0 mIU/L)
- Morning plasma cortisol >= 20 µg/dL
- Normal fasting glucose
- Urinalysis free of clinically significant abnormalities NOTE: Fasting is defined as no oral intake except water for at least 8 hours prior to the study visit.
- Female subjects of reproductive potential (girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months or have not undergone surgical sterilization [e.g., hysterectomy, bilateral oophorectomy, or salpingotomy]) must have a negative spot urine pregnancy test result (with a sensitivity of at least 50 mIU/mL) performed at entry, before initiating study medication.
- All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, or in vitro fertilization). If participating in sexual activity that could lead to pregnancy, the subject/partner must agree to use two reliable methods of contraception simultaneously (condoms with a spermicidal agent; or a diaphragm or cervical cap with spermicide) while on study drug and for 30 days after stopping the medication.
- Female subjects, who are not of reproductive potential, are eligible without requiring the use of contraception. Male subjects must use a condom with every sexual act that could lead to pregnancy.
- NOTE: Acceptable documentation of sterilization is either written or oral documentation communicated by clinician or clinician's staff of one of the following: physician report/letter: operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy); discharge summary; laboratory report of azoospermia; or FSH measurement elevated into the menopausal range as established by the reporting laboratory.
- Karnofsky performance score >= 80 within 30 days prior to study entry.
- Ability and willingness of subject to give written informed consent.
- Willingness to return for a follow-up visit on day 56.
- Subjects taking any precautionary concomitant medications (see section 5.2.2) must be on stable doses for >8 weeks prior to study entry and have no plans to change medications or doses for the duration of the study.
Who cannot join
- Receipt of anti-hepatitis C therapy within the 4 weeks prior to study entry or intent to initiate ant-hepatitis C therapy within 60 days after entry.
- Clinical evidence of cirrhosis or decompensated liver failure.
- Chronic or acute adrenal failure, history of active hepatitis B, HIV-1 infection, porphyrias, known moderate to severe cirrhosis, hemorrhagic disorders, concurrent anticoagulant therapy, any prior pituitary tumor, surgery, radiation treatment, or pituitary failure.
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
- Breast-feeding.
Show all 16Show fewer
- Dysfunctional uterine bleeding within the 12 months prior to study entry.
- Any current hormonal contraception or IUD use.
- Use of drugs that are inhibitors or inducers of metabolism by the CYP 3A4 within 7 days of study entry.
- Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry.
- Use of any cytotoxic chemotherapy, immunomodulators or investigational therapy within 90 days prior to study entry.
- Any vaccination within 30 days prior to study entry.
- Allergy to mifepristone or its formulation.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirement.
- Weight < 40 kg.
- Any other condition thought by the investigator that may interfere with the patient's ability to comply with the study protocol.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Connecticut
Farmington, Connecticut, 06030
Orlando Clinical Research Center
Orlando, Florida, 32809
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Saint Louis University
St Louis, Missouri, 63104
About this study
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
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 (i.e. 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.
Read the 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 mg/kg for 6 months in rats and macaques). In addition, chronic administration (up to 200 mg/day) 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 IU/ml, 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 4.5 and 5.4 μM, respectively (9).
- Conditions
- Hepatitis C Virus Infection
- Being tested
- VGX-410 (Mifepristone), Placebo
- Keywords
- Hepatitis C
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VGX-410 (Mifepristone)Drug
Also called Mifepristone
VGX-410 tablets taken daily or twice daily for 28 days
PlaceboDrug
Placebo for VGX-410 tablets taken daily or twice daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| 150 mg daily | Active comparator | Not described Receives: Drug: VGX-410 (Mifepristone) |
| 300mg daily | Active comparator | Not described Receives: Drug: VGX-410 (Mifepristone) |
| 300mg twice daily | Active comparator | Not described Receives: Drug: VGX-410 (Mifepristone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Log Change in Viral Load From Baseline (Day 1) to Day 28
Mean log change in HCV RNA viral load (significant reduction is considered >0.5 log 10) from baseline (Day 1) following once or twice daily dosing for 28 days at the 28 day timepoint
Measured: Baseline (Day 1) to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2005 (estimated)
- Study startNov 2005
- Primary completionSep 2007
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- VGX Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bruce Bacon, M.D., Principal investigator, St. Louis UniversityPablo Tebas, M.D., Principal investigator, University of PennsylvaniaGeorge Wu, MD, Principal investigator, University of ConnecticutThomas Marbury, MD, Principal investigator, Orlando Clinical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00255177
- Sponsor's protocol ID
- VT003
- Other IDs
- Viral Genomix, Inc. (VGX), 450 Sentry Parkway, Blue Bell, PA 19422, C. Jo White, M.D.
- Status last verified
- Oct 2009
- First submitted
- 15 Nov 2005
- Last updated
- 3 Nov 2009
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kieft JS, Zhou K, Jubin R, Doudna JA. Mechanism of ribosome recruitment by hepatitis C IRES RNA. RNA. 2001 Feb;7(2):194-206. doi: 10.1017/s1355838201001790.
PubMed 11233977
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00255177
- Acronym / sponsor ID
- VT003
- Conditions
- Hepatitis C Virus Infection
- Keywords
- Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- VGX Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Sep 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 17 Nov 2005 (estimated)
- Results
- Posted 23 Sep 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (i.e. 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 mg/kg for 6 months in rats and macaques). In addition, chronic administration (up to 200 mg/day) 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 IU/ml, 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 4.5 and 5.4 μM, respectively (9).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| 150 mg daily | Active comparator | Drug: VGX-410 (Mifepristone) |
| 300mg daily | Active comparator | Drug: VGX-410 (Mifepristone) |
| 300mg twice daily | Active comparator | Drug: VGX-410 (Mifepristone) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Hepatitis C infection for ≥ 1 year. Viral load at entry will be measured by the Amplicor Hepatitis C Virus Test Version 2.0 (Roche Molecular Systems; Plesasanton, CA) and genotyped by Trugene HCV 5'NC Genotyping kit (Visible Genetics; Toronto, Canada) performed within 90 days prior to study entry by a lab(s) certified for the assays.
- Male or female ages 18-65 years, inclusive.
- Plasma hepatitis C RNA of >105 copies/mL (or equivalent international units)
- Laboratory values: stable hepatic, renal, and hematological indices obtained within 30 days prior to study entry, as follows:
- Female subjects of reproductive potential (girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months or have not undergone surgical sterilization [e.g., hysterectomy, bilateral oophorectomy, or salpingotomy]) must have a negative spot urine pregnancy test result (with a sensitivity of at least 50 mIU/mL) performed at entry, before initiating study medication.
Key exclusion criteria (16 listed)
- Receipt of anti-hepatitis C therapy within the 4 weeks prior to study entry or intent to initiate ant-hepatitis C therapy within 60 days after entry.
- Clinical evidence of cirrhosis or decompensated liver failure.
- Chronic or acute adrenal failure, history of active hepatitis B, HIV-1 infection, porphyrias, known moderate to severe cirrhosis, hemorrhagic disorders, concurrent anticoagulant therapy, any prior pituitary tumor, surgery, radiation treatment, or pituitary failure.
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VGX-410 (Mifepristone)Also: MifepristoneVGX-410 tablets taken daily or twice daily for 28 days | Drug | 150 mg daily, 300mg daily, 300mg twice daily |
| PlaceboPlacebo for VGX-410 tablets taken daily or twice daily for 28 days | Drug | Placebo |
Primary outcome
Mean Log Change in Viral Load From Baseline (Day 1) to Day 28
Time frame: Baseline (Day 1) to Day 28
Mean log change in HCV RNA viral load (significant reduction is considered >0.5 log 10) from baseline (Day 1) following once or twice daily dosing for 28 days at the 28 day timepoint
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2009.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11233977Kieft JS, Zhou K, Jubin R, Doudna JA. Mechanism of ribosome recruitment by hepatitis C IRES RNA. RNA. 2001 Feb;7(2):194-206. doi: 10.1017/s1355838201001790.
Related trials for Hepatitis C Virus Infection
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Bacon, M.D. principal investigator
St. Louis University
Pablo Tebas, M.D. principal investigator
University of Pennsylvania
George Wu, MD principal investigator
University of Connecticut
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VGX-410 (Mifepristone) in people with Hepatitis C Virus Infection, run by VGX Pharmaceuticals, LLC at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Log Change in Viral Load From Baseline (Day 1) to Day 28 (time frame: Baseline (Day 1) to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00255177, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2009; AzTrials last refreshed its copy on 8 Nov 2026.