Comparative Effectiveness and Tolerability of Boceprevir vs Telaprevir

Study Overview
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Brief Summary
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The primary objective is to study the comparative effectiveness and tolerability of boceprevir vs. telaprevir in HCV treatment, within the VA population. The secondary objective: Resource use: recording of differences in resource use, such as direct costs (e.g., drug acquisition costs) and other indirect cost (e.g., staff utilization etc.) as the study will not only derive data by comparing those two drugs but also study the effect on different treatment lengths.

Detailed Description
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This is a randomized clinical trial comparing the effectiveness and safety of boceprevir and telaprevir. Recruitment of current eligible subjects will occur during their regular appointments at the Hepatitis C clinic. Eligible patients will have already been cleared for Hepatitis C treatment through their screening period which is including blood work, liver biopsy, urine collection/analysis, pregnancy screening and behavioral/mental health screening. On one of their standard visits to the Hepatitis C clinic, the health care provider(who is also research staff) or research staff will provide a consent form that the patient may take home and read more about the study. On the day of enrollment, which will also be the first day of treatment, health care providers within the Hepatitis C clinic will describe the study to the patient or refer them to one of the research for completion of these tasks. The consent form will be explained in detail at this meeting, and the patient will have the opportunity to ask questions and make comments about the study. Study subjects will initially be stratified into 6 groups (1a. treatment naives without cirrhosis and b. with compensated cirrhosis ; 2a. prior treatment experienced non-responders without cirrhosis and b. with cirrhosis; 3a. prior treatment experienced relapsers without cirrhosis and b. with cirrhosis). Patients in each of these groups will be randomized using random number table and allocation concealment will be achieved by using serially numbered, opaque, sealed envelopes into one of two study groups. The first group will receive boceprevir with Peg-IFN and ribavirin as indicated by package insert, and the second group will receive telaprevir with Peg-IFN and ribavirin as indicated by its package insert. All other stratified groups will receive protease inhibitor therapy as indicated by the FDA product labeling. Safety and effectiveness assessments will be conducted at study entry, PI therapy week 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 42 and 48, if applicable. Those are SOC visits during the treatment period and they will include blood tests, complete review of systems, and physical exams. Patients in all groups will be assessed for sustained viral response (SVR) at 12 and 24 weeks after the last dose of the medication is administered. Identical to SOC, safety and effectiveness assessments will be determine by health care providers and the adjudication committee, the latter of which will be unaware of the treatment arm of the patients. Members of the adjudication committee will be independent of the treating clinicians, and will be responsible for adjudicating the following outcomes: Viral response Adverse effects Decision regarding treatment discontinuation, based on adverse effect or virological failure

Official Title
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Comparative Effectiveness and Tolerability of Boceprevir vs Telaprevir and Re-assessment of Treatment Duration in Patients With Chronic Hepatitis C

Conditions
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Cirrhosis, Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Boceprevir
* Drug: Peg-IFN
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Have HCV genotype 1 infection and evidence of chronic hepatitis, as confirmed by a liver biopsy completed within three years prior to enrollment in the study, patients with cirrhosis will not need to undergo biopsy. Patients with compensated liver cirrhosis will be eligible. Patients who have previously been treated under standard of care (Peg-IFN, Ribavrin) and were non-responders, partial responders, or relapsers will also be eligible. Platelet count >60,000/mm3 Absolute neutrophil count > 1000/mm3 Hemoglobin >11.0 g/dL for females or >12.0 g/dL for males Serum creatinine </=1.5 mg/dL Adequately controlled DM Normal or adequately controlled TSH on prescription medication All other clinical laboratory values within normal limits, unless judged not clinically significant by the investigator Sterile or infertile (defined as vasectomy, tubal ligation, postmenopausal, or hysterectomy), or willing to use an approved method of double-barrier contraception (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of first dose administration until 6 months after the last dose Capable of understanding instructions, adhering to study schedules and requirements, and willing to provided informed consent Exclusion Criteria: Positive HIV or HbsAg serology Severe psychiatric or neuropsychiatric disorders including, but not limited to uncontrolled severe depression, history of suicidal ideations or suicide attempt(s), as determinate by SOC psychological evaluation 3 History or clinical manifestations of significant metabolic, hematological, pulmonary, ischemic or unstable heart disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic (including severe retinopathy), or immune mediated disease 4. Chronic hepatic diseases other than hepatitis C 5. Organ or bone marrow transplant 6. Chronic (greater than 30 days) use of immunosuppressive medications including steroids in doses equivalent to 10 mg of prednisone or higher, 30 days prior to and anytime during the course of the study 7. Female patients who are breast-feeding or have a positive pregnancy test at any time during the study 8. Males whose female partners are pregnant 9. Patients who have had a malignancy diagnosed and/or treated within the past 3 years, except for localized squamous or basal cell cancers treated by local excision 10. Patients who have participated in a clinical trial and have received an investigational drug within 30 days prior to screening 11. Current alcoholism or drug addiction

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Telaprevir<br>Telapravir was administer with Peg-IFN and Ribavirin as per package insert Dose Telaprevir : PO, tablet 1125 mg BID for 12 weeks | Drug: Telaprevir<br> <br> * Other names: INCIVEK;Drug: Peg-IFN<br>* Administration 45-180mcg in 0.5 ml solution s.c. weekly for 24-48 weeks<br>* Other names: Peg-Interferon alfa-2a, Pegasys;Drug: Ribavirin<br>* Administration: 200 mg capsules; 800 mg-1200 mg daily for 24-48 weeks<br>* Other names: Copegus;|
| Active Comparator: Boceprevir<br>Boceprevir was administer with Peg-IFN and Ribavirin as per package insert Dose Boceprevir PO capsule, 800mg TID for up to 44 weeks | Drug: Boceprevir<br> <br> * Other names: Victrelis;Drug: Peg-IFN<br>* Administration 45-180mcg in 0.5 ml solution s.c. weekly for 24-48 weeks<br>* Other names: Peg-Interferon alfa-2a, Pegasys;Drug: Ribavirin<br>* Administration: 200 mg capsules; 800 mg-1200 mg daily for 24-48 weeks<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/Adverse Event Outcome Measure | Number of Participants with Serious and Non-Serious Adverse Events | Up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C treatment,, Boceprevir,, Telaprevir,, Safety, Effectiveness, Head-to-head trial