| Eligibility |
Inclusion Criteria:
- Provision of written informed consent;
- Male and female patients aged 18 years and over;
- For Cohort One: willing to use two effective methods of contraception during the
treatment period and 24 weeks post;
- For Cohort Two and Three: If female and of childbearing potential, willing to use at
least one effective method of contraception during the treatment period and 4 weeks
post; women not of childbearing potential include those who are postmenopausal or
permanently surgically sterile (no contraception is required for male participants);
- For Cohort One, Two and Three: Females of child-bearing potential must have a negative
pregnancy test at screening and immediately prior to first dose of study drugs;
- HCV genotype 1 infection at screening (Cohort 1 only);
- Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the
investigator is unlikely to demonstrate spontaneous viral clearance;
- Absence of cirrhosis, as defined by one of the following:
- Liver biopsy within 24 months prior to or during screening demonstrating absence
of cirrhosis (eg, METAVIR fibrosis score = 3, Ishak fibrosis score = 4); or
- FibroScan score < 12.5 kPa within = 6 months of screening or during screening
period; or
- Medically stable on the basis of physical examination, medical history and vital
signs;
- Adequate English to provide reliable responses to the study questionnaires;
- Recently acquired HCV infection (estimated duration of infection =12 months) as
defined by*:
1. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii)
Documented anti-HCV Ab negative within the 18 months prior to anti-HCV antibody
positive result
OR
2. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii)
Acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the previous 12
months prior to first positive HCV antibody or HCV RNA, with no other cause of
acute hepatitis identifiable
OR
3. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii)
Acute asymptomatic hepatitis (acute rise in ALT> 5 X ULN) within the previous 12
months prior to first positive HCV antibody or HCV RNA and documented normal ALT
within the previous 12 months with no othercause of acute hepatitis identifiable
(In individuals with a previously high ALT, an acute rise to >3.5 x their
previous peak ALT in last 12 months is acceptable)
OR
4. For cases of recent HCV reinfection the following criteria are required:
Documented prior HCV antibody positive with HCV RNA negative on at least 2
occasions 6 months apart AND new HCV RNA positive within the previous 6 months.
* Estimated duration of infection based on midpoint between last antibody or RNA
negative and first antibody or HCV RNA positive in the case of seroconversion and
6 weeks prior to date of maximum ALT in the case of acute hepatitis.
If co-infection with HIV is documented, the subject must meet the following
criteria:
Cohort One:
- On a stable qualifying ARV regimen for >8 weeks prior to screening visit, with CD4 T
cell count >200 cells/mm3 and a plasma HIV RNA below the limit of detection.
Cohort Two:
• On a stable qualifying ARV regimen for >8 weeks prior to screening visit, with CD4 T cell
count >200 cells/mm3 and a plasma HIV RNA below the limit of detection.
OR
• ARV naïve with CD4 T cell count >500 cells/mm3
Exclusion Criteria:
- Pregnancy/lactation
- Infection or co-infection with an HCV genotype other than 1 (Cohort 1 only)
- Subject has current or past clinical evidence of decompensated liver disease, such as
ascites, hepatic encephalopathy, oesophageal varices, and/or any of the following
screening laboratory results;
- International Normalized Ration (INR) > 1.5;
- Patients with a known inherited blood disorder and INR > 1.5 may be enrolled
after discussion with the Principal Investigator
- Serum albumin <3.3 g/dL;
- Serum total bilirubin >1.8 x upper limit of normal (ULN), unless isolated in
subjects with Gilbert's syndrome;
- Subject shows evidence of significant liver disease in addition to hepatitis C, which
may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune
hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis (NASH), or
primary biliary cirrhosis;
- Subject has active malignant disease or history of malignant disease within the past 5
years (with the exception of treated basal cell carcinoma);
- History of chronic pulmonary disease associated with functional limitation, severe
cardiac disease, major organ transplantation or other evidence of severe illness,
malignancy, or any other conditions which would make the patient, in the opinion of
the investigator, unsuitable for the study;
- Poorly controlled diabetes mellitus as evidenced by haemoglobin A1c (HbA1c) =8.5%;
- Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment
(including supraphysiologic doses of steroids and radiation) =6 months prior to the
first dose of study drug
- Prior treatment failure with an HCV protease inhibitor;
- Any investigational drug =6 weeks prior to the first dose of study drug;
- Positive test at screening for anti-HAV IgM Ab, anti-HBc IgM Ab or HBsAg;
- Confirmed presence of hepatocellular carcinoma indicated on imaging techniques such as
computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months
prior to screening or on an ultrasound performed at screening (a positive ultrasound
result will be confirmed with CT scan or MRI);
- Subject has history of organ transplant that requires chronic immunosuppression
- Corneal, skin, and hair grafts are allowed;
- History of severe psychiatric disease that in the opinion of the investigator is
unstable enough to compromise treatment adherence;
- Subject has evidence of serious or severe bacterial or fungal infection(s), including
active tuberculosis;
- Prohibited medications and herbal remedies as detailed in section 5.5;
- Screening laboratory tests showing any of the following abnormal results:
- Haemoglobin <100 g/L
- Calculated creatinine clearance <50mL/min
- Platelets <100,000 cells/mm3
- Absolute neutrophil count (ANC) <1,500 cells/µL.
|
