A Pilot Trial of Safety and Efficacy of Telaprevir +Peginterferon +Ribavirin +Vitamin D3 v. Telaprevir +Peginterferon +Ribavirin Among Treatment-naive Veterans With Genotype 1 Hepatitis C Virus

Inclusion Criteria:

- Chronic Hepatitis C genotype 1 infection with serum HCV RNA quantifiable at ≥ 10,000
IU/ml at time of screening and a positive anti-HCV antibody test or evidence of
chronic infection.

- No prior treatment (treatment naïve) with peginterferon, ribavirin or any other
anti-HCV drugs.

- Age greater or equal to18 years

- Agree to genetic testing for IFN-λ3 (formerly called IL-28B) genotype associated with
response to peginterferon/ribavirin treatment

Exclusion Criteria:

- Liver disease other than from hepatitis C (e.g., hepatitis B, NASH, hemochromatosis,
autoimmune hepatitis, etc.).

- HCV infection with mixed genotypes (e.g., genotypes 1&2, 1&3, or 1&4)

- Decompensated liver disease (current or past history of clinically detectable
ascites, bleeding esophageal varices, hepatic encephalopathy, or hepatocellular
carcinoma)

- AFP>100ng/ml. Subjects with AFP ≥ 25 and ≤ 100 ng/mL can be enrolled if they have
had a high quality US, CT or MRI within the past 3 months demonstrating no evidence
of a mass in the liver suggestive of hepatocellular carcinoma

- Known HIV infection

- Serum 25(OH)D less than 12ng/ml or greater than 30ng/ml at screening

- Regular vitamin D supplement use (either alone or in combination with other vitamins
or minerals; calcium intake not exceeding 400 IU/day acceptable) or use of a sun
tanning bed, within 3 months prior to the start of the study

- Regular calcium supplement use (either alone or in combination with other vitamins or
minerals; multivitamin dose not exceeding 200mg/day acceptable) within 30 days prior
to the start of the study

- Refusal to abstain from vitamin D supplementation (multivitamin dose not exceeding
400 IU/day acceptable), calcium supplementation (multivitamin dose not exceeding
200mg/day acceptable), prolonged sunbathing (>1 hour/week), and the use of a sun
tanning bed throughout the study

- Current or past history of kidney stones

- Current use of any of the prohibited medications listed in section 5.5 and the
INCIVEK® package insert.

- Need for therapeutic vitamin D or calcium (e.g. treatment for osteoporosis,
osteomalacia, hyperparathyroidism etc.), in the opinion of the investigator

- Significant substance abuse within the past 6 months, excluding the use of marijuana,
or ongoing alcohol use exceeding 1 drink/day (in the opinion of the investigator)

- Suicidal attempt in the past 10 years or suicidal ideation in past 3 months, or any
other psychiatric condition that the investigator deems would make a subject unsuited
for treatment with peginterferon or ribavirin. (Subjects with mild or moderate
depression or other psychiatric conditions who obtain written clearance for HCV
treatment from their VA psychiatrist would be eligible for the study.)

- Confirmed or suspected malignancy, or history of malignancy within the past 3 years
(except treated basal cell carcinoma of the skin or in situ carcinoma of the uterine
cervix)

- Any autoimmune disease not easily controlled (in the opinion of the investigator)

- Any condition resulting in malabsorption (celiac disease, amyloidosis, chronic
pancreatitis, IBD, cystic fibrosis etc) or significant gastric resection (e.g.,
Bilroth II)

- Poorly controlled thyroid disorder, or diabetes mellitus (HbA1c > 9)

- Glomerular diseases (e.g., glomerulosclerosis or glomerulonephritis) associated with
a serum creatinine >1.5 times the upper limit of normal

- Current or history of any clinically significant cardiac abnormalities/dysfunction
(eg, angina, congestive heart failure, myocardial infarction, pulmonary hypertension,
complex congenital heart disease, cardiomyopathy, significant arrhythmia) including
current uncontrolled hypertension or history of use of antianginal agents for cardiac
conditions (Inclusion will be considered if clearance by a cardiologist is
obtained.)

- Receipt of an investigational drug within the past 30 days

- Females who have a positive pregnancy test at the time of screening, are
breastfeeding or who anticipate pregnancy within the next 18 months, or men with
pregnant partners

- Lack of agreement from subject to use two forms of acceptable contraception

- History or other evidence of any significant illness which, in the opinion of the
investigator, would make the patient, unsuitable for the study

- Laboratory Exclusions

Hemoglobin: <12gm/dl male or female

Neutrophil: <1,200/mm3

Platelets: <90,000/mm3

INR: >1.5

Albumin: <3.2gm/dl

Total Bilirubin: >2.0mg/dl

HbA1c: >9.5%

Serum Creatinine: >1.5 times the upper limit of normal

Alpha-fetoprotein: >100ng/ml If AFP >25ng/ml yet <100ng/ml a recent (<3months) US, CT, or
MRI showing no mass suggestive of HCC is required

Serum Calcium Within local laboratory normal range

Parathyroid hormone (PTH) <10 or >55 pg/mL