Technology-Based Application To Improve The Triple Therapy Adherence Rate In Subjects With Hepatitis C Infection

This protocol is a Phase II Open Label Clinical Trial of a technology-based application
"On-Plan" (OP) which is expected to improve adherence to boceprevir-based triple therapy in
subjects with chronic genotype 1 hepatitis C infection compared to historical controls from
the University of Louisville. OP uses a combination of smart phone and computer-based social
support to correct non-adherence and manage side effects as well as contingency management
(positive reinforcement) when patient-reported compliance is documented by pill counts
and/or electronic compliance monitors. 52 consenting subjects prescribed boceprevir-based
triple therapy for chronic genotype 1 HCV according the U.S. prescribing information will be
enrolled and all will receive the OP application. A Simon's two stage procedure will be
utilized to minimize risk while preliminary efficacy/safety data are collected on this
innovative "app" for HCV therapy.

Inclusion Criteria:

The subject must meet ALL of the criteria listed below for entry:

1. Each subject must be willing and able to provide written informed consent for the
trial.

2. Subjects must be willing to adhere to dose and visit schedules.

3. Each subject must be > 18years of age.

4. Each subject's weight must be ≥ 40 kg and ≤ 125 kg.

5. Subject must have previously documented HCV genotype 1 infection. Subjects with other
or mixed genotypes are not eligible. The HCV-RNA result obtained from the central
laboratory at the Screening Visit must confirm HCV genotype 1 infection with HCV RNA
>10,000 IU/mL. Patients may be either treatment naïve or previously treated as long
as they have not been treated with a protease inhibitor. Patients may have
compensated cirrhosis.

6. Subject and subject's partner(s) must each agree to use acceptable methods of
contraception for at least 2 weeks prior to Day 1 and continue until at least 6
months after last dose of study medication, or longer if dictated by local
regulations. Postmenopausal women are not required to use contraception.
Postmenopausal is defined as at least 12 consecutive months without a spontaneous
menstrual period. Each sexually active male subject with a female partner(s) of
child-bearing potential must also provide written informed consent to provide
information regarding any pregnancy.

Exclusion Criteria:

The subject will be excluded from entry if ANY of the criteria listed below are met:

1. Subject is under the age of legal consent, is mentally or legally incapacitated, has
significant emotional problems at the time of pre-study screening visit or expected
during the conduct of the study or has a history of a clinically significant
psychiatric disorder which, in the opinion of the investigator, would interfere with
the study procedures.

2. Subjects co-infected with the human immunodeficiency virus (HIV) or hepatitis B virus
(Hepatitis B surface antigen [HBsAg] or HIV positive.

3. Treatment for hepatitis C with any investigational medication. Prior treatments with
herbal remedies with known hepatotoxicity are exclusionary. All herbal remedies
including but not limited to St. John's Wort (Hypericum perforatum) used for
hepatitis C treatment must be discontinued before Day 1. Only silibinin based
products such as silymarin (milk thistle) are allowed during the trial.

4. Subjects receiving any of the following medication(s) within 2 weeks prior to the Day
1 visit that are highly dependent on CYP3A4/5 for clearance, and for which elevated
plasma concentrations could be associated with serious and/or life-threatening events
such as orally administered midazolam, pimozide, amiodarone, flecainide, propafenone,
quinidine, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine,
methylergonovine). The following medications are also exclusionary if taken within 2
weeks prior to the Day 1 visit: alfuzosin, cisapride, triazolam, sildenafil, and
tadalafil (the latter 2 only if they are used for the indication of chronic
obstructive pulmonary disease (COPD).

5. Participation in any other clinical trial within 30 days of the screening visit in
this trial or intention to participate in another clinical trial during participation
in this trial. Collection of additional blood, urine, or tissue samples or additional
data, beyond that specified in this protocol, is prohibited (other than that related
to the subject's medical care).

6. Evidence of decompensated liver disease.

7. Subject has evidence of hepatocellular carcinoma (HCC) or is under evaluation for
HCC.

8. Subject is diabetic and/or hypertensive with clinically significant ocular
examination findings within 6 months prior to the screening visit or between the
screening visit and Day 1: retinopathy, cotton wool spots, optic nerve disorder,
retinal hemorrhage, or any other clinically significant abnormality.

9. Subject has pre-existing psychiatric condition(s) including but not limited to:
Current moderate or severe depression or history of severe psychiatric disturbance.

10. Subject has a clinical diagnosis of substance abuse which the investigators of the
following specified drugs within specified timeframes:

1. Alcohol, intravenous drugs, inhalational (not including marijuana),
psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs:
within 1 year of the screening visit, OR

2. Multi-drug abuse (e.g., two or more of the substances listed in Exclusion
Criterion 10a within 3 years of screening visit, OR

3. Subjects receiving opiate agonist substitution therapy within 1 year of
screening visit (except for those subjects monitored in an opioid substitution
maintenance program as specified in Section 7.3.5) OR

4. Subject's historic marijuana use is deemed excessive by a physician investigator
or is interfering with the subject's daily function. If subject's marijuana use
is not deemed excessive and does not interfere with daily function, subject must
be instructed to discontinue any current use of recreational marijuana prior to
entry into trial and throughout the trial period.

11. Subject has any known medical condition that could interfere with the subject's
participation in and completion of the trial, including, but not limited to:

1. Central nervous system (CNS) trauma requiring intubation, intracranial pressure
monitoring, brain meningeal or skull surgery, or resulting in seizure, coma,
permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid
(CSF) leak. Prior brain hemorrhage and/or intracranial aneurysms (whether
adequately repaired or not).

2. Current uncontrolled seizure disorder unless now controlled on stable medical
regimen that does not interact with boceprevir.

3. History of stroke or transient ischemic attack.

4. Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's
disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic
thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic
anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected
treatment, or symptomatic thyroid disorder).

5. Clinically significant chronic pulmonary disease (e.g., clinical chronic
obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis,
sarcoidosis).

6. Current or history of any clinically significant cardiac
abnormalities/dysfunction (e.g., angina, congestive heart failure, myocardial
infarction, pulmonary hypertension, complex congenital heart disease,
cardiomyopathy, significant arrhythmia) including current uncontrolled
hypertension, history of use of antianginal agents for cardiac conditions, or
clinically significant abnormality on ECG performed at the pre-study screening
visit.

7. Any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids during the course of the trial.

8. Clinically significant gout within the last year.

9. Clinically significant hemoglobinopathy, including, but not limited to,
thalassemia major.

10. Myelodysplastic syndromes.

11. Coagulopathy, including, but not limited to, hemophilia.

12. Organ transplants (including hematopoietic stem cell transplants) other than
cornea and hair.

13. Poor venous access that precludes routine peripheral blood sampling required for
this trial.

14. Subject with a history of gastric surgery (e.g., stapling, bypass) or subject
with a history of malabsorption disorders (e.g., celiac sprue disease).

p) Other serious medical condition which could be exacerbated by peg-IFN alfa-2a
and/or RBV, in the opinion of the investigator.

12. Subject has evidence of active or suspected malignancy, or a history of malignancy,
within the last 5 years (except adequately treated carcinoma in situ and basal cell
carcinoma of the skin. Subjects under evaluation for malignancy are not eligible.

13. Female subject is pregnant, lactating, expecting to conceive or donate eggs OR Male
subject is planning to impregnate or provide sperm donation or has a female sexual
partner who is pregnant or is of childbearing potential and is unwilling to commit to
using two methods of birth control throughout treatment and after the completion of
all treatment (see Inclusion Criterion).

14. Subject has any other condition which, in the opinion of the principal investigator
or physician, would make the subject unsuitable for enrollment or could interfere
with the subject participating in and completing the study.

15. Subject had a life-threatening SAE during the screening period.

16. Subject is a member or a family member of the investigational study staff or sponsor
staff directly involved with this study.

Laboratory Exclusion Criteria Note: If any of the laboratory exclusion criteria are met,
the site may have the subject retested. If a single value is within 10% of the listed
laboratory exclusion criterion value, and the value is considered not clinically
significant by the investigator, the subject may be considered for enrollment. The value
for platelets counts cannot be retested.

1. Hemoglobin <10 g/dL for females and <11 g/dL for males.

2. Neutrophils <1500/mm3, or <1,200/mm3 for subjects of African descent.

3. Platelets <60,000/mm3; this may not be retested and there is no variance allowed for
this entry criteria.

4. Thyroid disorders:

1. The subject may be enrolled if clinically euthyroid, AND

2. The euthyroid function is confirmed by thyroxine/triiodothyronine (T4/T3)
testing.

5. Serum glucose: Hemoglobin A1C >8.5%.

6. Positive pregnancy test.