Antiviral Activity and Safety of 3 Different Doses of Mifepristone in Hepatitis C Infected Patients
Condition: Hepatitis C Virus Infection
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: VGX-410 (Mifepristone); Placebo
Intervention description: VGX-410 tablets taken daily or twice daily for 28 days; Placebo for VGX-410 tablets taken daily or twice daily for 28 days
Intervention MeSH terms: Mifepristone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hepatitis C

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 (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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

               -  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.

        Exclusion Criteria:

          -  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.

          -  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.