Digimeds to Optimize Adherence in Patients With Hepatitis C and Increased Risk for Nonadherence

Hepatitis C virus (HCV) is a preventable and curable blood-borne virus. Adherence to HCV
therapies is essential to achieve sustained virologic response (SVR) or cure. New
direct-acting agents (DAA) are now available, such as fixed-dose combination of ledipasvir
and sofosbuvir, which is given once daily with or without ribavirin to treat HCV infection in
8-12 weeks, which can cure hepatitis C with a once daily regimen.

which is given once daily with or without ribavirin to treat HCV infection in 8-12 weeks.

Providers and third-party payers are concerned that patients use these high-cost therapies as
prescribed and obtain the intended value of their treatment, so as to prevent otherwise
avoidable medicine wastage and re-treatment. Some HCV-infected patients are currently
excluded from using the newer direct-acting therapies because they are considered to have a
high risk of not completing their intended treatment, or they do not have access to care due
to other issues like transportation difficulties.

Additionally, third party payers and providers have proposed to assess patient adherence
during treatment with HCV RNA level and additional adherence assessments. However,
determining adherence to anti-viral therapy based upon decreases that are observed in RNA
titers at intermittent intervals, or periodic assessments of medication use, subsequent to
therapy initiation are indirect and retrospective. Additionally, this practice can be a
burden for patients, especially those who live far away from their providers.

Proteus Discover™ provides wirelessly observed therapy (WOT) for passive direct, timely
confirmation of medication ingestion. Proteus Discover includes a FDA cleared and CE-marked
device, which consists of three components: 1) an Ingestible Sensor (IS) embedded inside of a
placebo pill, which can be co-encapsulated with prescribed medication (CEM); 2) a wearable
sensor patch (herein referred to as the Proteus Patch), which passively detects and stores
time-stamped CEM ingestions, as well as physiological and behavioral metrics such as heart
rate and activity patterns (e.g., step count, time spent in physical activity, number of
hours of rest); and 3) software to aggregate and display Proteus Patch data. The offering
also includes the Proteus Discover App, which allows the subject to review and interact with
the data via a mobile device. Providers can view the data via the Proteus Discover Portal.

To provide WOT in this study, the Proteus Ingestible Sensor pill will be placed in a capsule
along with HCV medication by the patient's pharmacy to create a digital medicine version of
the therapy. The adhesive wearable sensor patch worn by the patient on the left lower torso
will be used for detection of CEM ingestions which are then displayed on a mobile application
for the patient, and on a web portal for physicians and the study healthcare teams to assist
them in identifying when support for the subject may be needed for taking medication
consistently.

Participants must have insurance or other method (e.g. patient assistance program) to pay
for medicine.

Inclusion Criteria:

- A subject must meet ALL of the following criteria to be considered for enrollment into
this study:

1. Adults (≥18 years old) who are diagnosed with hepatitis C deemed chronic by the
investigator

2. Candidate for treatment for oral direct acting agent for hepatitis C such as
fixed-dose velpatasvir and sofosbuvir; fixed-dose ledipasvir and sofosbuvir; or
fixed-dose glecaprevir and pibrentasvir with insurance coverage for therapy.
Subjects may take other medicines that will not be co-encapsulated (e.g.
ribavirin)

3. One of more of the following risk factors for nonadherence:

1. Active alcohol or substance abuse (positive urine drug screen, illicit use
in past 3 months, and/or in opioid substitution program), OR

2. Patient reported history of hospitalization within past 2 years for a
psychiatric comorbidity, OR

3. Evidence of nonadherence to medications (e.g. self-report or refill history
indicative of nonadherence), OR

4. History of at least one missed clinic visit for hepatitis management, OR

5. Patient-reported history of one or more transportation barriers (e.g. burden
due to time and/or distance or lack of access to regular transportation) to
healthcare access, which creates a risk for missed or delayed care

4. Study subject has daily access to a telephone for communicating with the study
personnel and study personnel contacting the study subject

5. Ability to read and understand the instructions for the study.

6. Willingness to adhere to all study procedures (both onsite and offsite),
including troubleshooting of the product by a third-party, if needed.

7. Capacity to and willing to provide informed consent. All subjects must have a
signed informed consent document prior to participating in this study

8. Currently owns and uses a smart phone or tablet, or has capacity to learn use of
study mobile device as determined by investigator.

9. Adequate data connectivity at home via cellular service and/or access to a secure
wireless internet (WiFi) network with the proficiency to connect a mobile device
to the WiFi network.

- Note: None of the five individual sub-criteria (i.e., 3a, 3b, 3c, 3d, or 3e)
alone may be used to qualify more than approximately 20% of the total study
population for randomization. For example, "3d" may be used to qualify no
more than 20% of the study population for randomization without an
additional sub-criteria also being met (e.g., "3d" + "3a"). The data center
will monitor the use of these five enrolment sub-criteria, and study sites
will be notified when qualification for enrollment may no longer be based
upon meeting only a specific one of the five sub-criteria alone (e.g., "3d"
alone).

Exclusion Criteria:

- ANY 1 of the following will exclude a subject from being enrolled into the study:

1. BMI > 40 kg/m2 2. Active skin infection or active dermatitis, OR history of chronic
inflammatory skin condition including psoriasis and chronic dermatitis (except atopic
dermatitis) 3. Allergy to adhesive bandages/tapes (e.g. Band-Aids®) 4. Severely
decompensated cirrhosis (Child-Pugh C) or a liver transplant candidate 5. Any
condition that in the investigator's opinion could preclude safe participation in the
study (e.g. contraindication to hepatitis C therapy) or would preclude the subject
from being able to participate in the study protocol requirements 6. Participating in
a drug study or medical device clinical study (including its safety follow-up period
as defined by protocol) 30 days prior to study start or completion 7. Unwilling to
take a gelatin capsule because it is manufactured from animal origins (e.g. for
religious reasons) 8. Allergy to food dye 10. Terminal illness (≤ 1 year of life
anticipated). 10. Currently known to be pregnant or nursing an infant. 11. For women
of childbearing potential, not using an acceptable form of contraception for at least
2 months prior to screening and throughout the duration of the study. Accepted means
of contraception include oral contraceptive or implant, condom, diaphragm, spermicide,
intrauterine device, tubal ligation, or partner with vasectomy.

12. Positive pregnancy test during screening 13. Inability to swallow the test capsule