Clinical trial NCT03164902: Digimeds to Optimize Adherence in Patients With Hepatitis C and Increased Risk for Nonadherence
Official title: Evaluation of Wirelessly Observed Therapy to Optimize Adherence in Patients With Hepatitis C and Increased Risk for Nonadherence to Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatitis C, Chronic
Nonadherence, Patient
Lead sponsor: Proteus Digital Health, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the ability of digital medicines, Proteus Discover, to promote adherence and thus achieving a cure for hepatitis C in patients at high risk for not adhering to their hepatitis therapy. In this single-arm, prospective study, subjects at high risk for nonadherence will be prescribed hepatitis C therapy that will be co-encapsulated with ingestible sensors (creating the digital medicine) by a pharmacy. Both the subject and the providers will have access to the ingestion adherence.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: SVR12 Rate
timeFrame: 12 weeks following completion of their hepatitis C therapy
Secondary outcomes:
measure: SVR4 Rate
timeFrame: 4 weeks following completion of their hepatitis C therapy
measure: Ingestion Adherence
timeFrame: 8 to 16 weeks (during therapy)
measure: Safety Profile:Summary details of all adverse events during the study
timeFrame: Up to 24 weeks
measure: Subject Satisfaction
timeFrame: 4 weeks following completion of their hepatitis C therapy
Other outcomes:
measure: Treatment efficiency
timeFrame: Up to 24 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Washington
country: United States
facility: Providence Health System
state: District of Columbia
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: Apex Clinical Research
state: Florida
city: Chicago
country: United States
facility: The Ruth M. Rothstein CORE Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Santa Fe
country: United States
facility: Southwest Care Center
state: New Mexico
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Madison
country: United States
facility: SSM Health Dean Medical Group
state: Wisconsin
Study officials:
affiliation: Johns Hopkins University
name: Mark Sulkowski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.
citation: Younossi ZM, Park H, Gordon SC, Ferguson JR, Ahmed A, Dieterich D, Saab S. Real-world outcomes of ledipasvir/sofosbuvir in treatment-naive patients with hepatitis C. Am J Manag Care. 2016 May;22(6 Spec No.):SP205-11.
citation: Sulkowski M, Luetkemeyer AF, Wyles DL, Martorell C, Muir A, Weisberg I, Gordon SC, McLain R, Huhn G. Impact of a digital medicine programme on hepatitis C treatment adherence and efficacy in adults at high risk for non-adherence. Aliment Pharmacol Ther. 2020 Jun;51(12):1384-1396. doi: 10.1111/apt.15707. Epub 2020 Apr 30.