Trial of MitoQ for Raised Liver Enzymes Due to Hepatitis C
Trial of MitoQ for Raised Liver Enzymes Due to Hepatitis C
A Phase 2, randomized, double-blind, parallel design trial of two doses of mitoquinone
 mesylate (MitoQ) and of placebo in patients with chronic Hepatitis C.

 MitoQ is a mitochondria-targeted antioxidant that rapidly permeates the lipid bilayer and
 accumulates within mitochondria in organs such as liver, brain, heart, skeletal muscle. There
 is strong evidence for increased oxidative stress and mitochondrial damage leading to
 apoptosis via caspase activation. Several studies have shown that MitoQ protects cells from
 apoptosis by acting as a caspase inhibitor and may be effective in reducing cell damage in
 liver disease.

 It is hypothesised that administration of MitoQ will lower raised ALT seen in patients with
 chronic Hepatitis C compared with placebo. Approximately 36 patients who have been
 unresponsive or not suitable for interferon-based therapy will be enrolled at one centre.
 Treatment duration will be 28 days with 28 days post-treatment follow-up.
Hepatitis C is a viral liver infection that contributes significantly to the burden of
 chronic liver disease. It is currently estimated that over 170 million individuals (3% of the
 world's population)are infected. In New Zealand, an estimated 25,000 people are living with
 hepatitis C virus (HCV) infection and prevalence is predicted to increase by 50% over the
 next 10 years. HCV is primarily spread by blood-to-blood contact. The single most important
 risk factor for acquiring HCV is the use of injected recreational drugs, accounting for
 approximately 80% of infections.

 Unlike hepatitis B, no hepatitis C vaccine is currently available. In the absence of an
 effective vaccine the current treatment of choice is interferon and ribavirin. However,
 treatment of chronic HCV infection with interferon-alpha monotherapy does not achieve
 sustained virologic response. Therefore, it is important to develop alternative treatment
 strategies for patients who are unresponsive or intolerant to current antiviral therapy.

 The aim of this protocol is to compare two doses of a mitochondrial antioxidant treatment
 (MitoQ) and placebo for the treatment of patients with raised liver enzymes due to HCV
 infection. Approximately 36 eligible patients with chronic HCV infection will be randomised
 to receive one of two doses of MitoQ or placebo in a 1:1:1 ratio. Treatment duration will be
 28 days with 28 days post-treatment follow-up.
Inclusion Criteria:

 1. Willing to adhere to study requirements as evidenced by providing written informed
 consent before initiation of any study-related procedures

 2. Aged between 18-65 years

 3. Documented history of chronic HCV infection (for at least 6 months prior to study
 entry) as diagnosed by either:

 1. Anti-HCV positive or

 2. HCV RNA viral load positive by PCR

 4. Be a non-responder to or unsuitable for interferon based therapy.

 5. Have liver inflammation, as defined by either AST and/or ALT levels 2-10 x ULN on at
 least 1 previous occasion within the past 6 months and at Pre-treatment visit

 6. alpha-fetoprotein (AFP) less than/equal to 50µg/L

 7. Hemoglobin ≥100g/L, platelet count ≥75x109/L, and white blood cell count ≥1.5x109/L

 8. Males, or females who are not of child-bearing potential or who are taking adequate
 contraceptive measures. Female patients must be postmenopausal for at least 2 years
 prior to the study, surgically sterile, or using effective contraception for at least
 2 months prior to starting study drug and until 28 days following the last dose of
 study drug. Acceptable methods of birth control include hormonal contraceptives, or
 double-barrier methods.Negative serum pregnancy test must be documented at the
 Pre-treatment visit (i.e. within 14 days of starting study drug)

 9. Liver biopsy within past 3 years showing stage 2 fibrosis only (i.e. excludes
 cirrhosis and cancer); or within past 6 years showing stage 0 or 1 (no or minimal
 scarring).

 Exclusion Criteria:

 1. Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or
 other imaging techniques)

 2. Presence of human immunodeficiency virus (HIV)

 3. Co-infection with hepatitis B virus (HBV)

 4. Last baseline AST and ALT level prior to Day 1 of <2.0xULN

 5. Renal impairment (creatinine>1.5 x ULN) or hepatorenal syndrome

 6. Chronic pancreatitis

 7. Hospitalization for liver disease within 60 days of the Pre-treatment visit

 8. Liver transplant recipients

 9. Use of drug therapy for Hepatitis C, including the use of:

 1. drugs with presumed anti-Hepatitis C activity in the past 3 months

 2. corticosteroids in the past 30 days

 3. drugs with medium to high risk of hepatotoxicity (including alpha methyl-dopa,
 sodium valproic acid, isoniazide, or nitrofurantoin) in the past 30 days

 10. Any patient who admits to using or has a positive screening test for: amphetamines,
 barbiturates, pethidine, benzodiazepine, cocaine, methadone, opiates, phencyclidine or
 propoxyphene (unless medically prescribed and in stable doses for at least 30 days)

 11. Alcohol consumption >5 units per week

 12. Any patient who has received any investigational drug or device within 30 days of
 dosing, or who is scheduled to receive another investigational drug or device during
 the course of this trial

 13. History of a malignancy other than treated basal cell or squamous cell carcinoma of
 the skin; those with a history of malignancy that has been treated with no recurrence
 within the last 2 years are not excluded

 14. Use of antioxidants (Coenzyme Q10 and idebenone) at doses ≥300mg/day within 120 days
 prior to enrolment. Doses between 25-300mg/day are not an exclusion and require a 7
 day washout prior to study enrolment

 15. Use of dietary supplements (vitamin or mineral) at constant doses throughout the study
 (unless medically prescribed). Patients choosing to stop using supplements are not
 excluded and require a 7 day washout period prior to study enrolment

 16. History of a hypersensitivity reaction to any components of the study drug or
 structurally similar compounds including Coenzyme Q10 and idebenone

 17. Unable to swallow tablets whole.