Hepatitis C MedDRA version: 16.1 Level: LLT Classification code 10019183 Term: HCV System Organ Class: 100000004848
Conditions
Interventions
Trade Name: Victrelis
Product Name: boceprevir
Product Code: SCH 503034
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: boceprev
Sponsors
Merck Sharp & Dohme Corp, a Subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Each subject must be willing and able to provide written informed consent for the trial. 2. Each subject must be ? 18years of age. 3. Each subject’s weight must be = 40 kg and = 125 kg 4. Subject must have previously documented CHC genotype 1 infection where genotyping is performed as standard of care. If genotyping is not considered standard of care, then determination can be done at screening. 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 ³10,000 IU/mL. 5. Subjects must have IL28b CC allele gene (with SNP rs12979860) 6. Subject without the evidence of cirrhosis and hepatocellular carcinoma. 7. Subject has had an ECG within 6 months without clinically significant abnormalities prior to the screening visit (or between the screening visit and Day 1). 8. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 450
Exclusion criteria
Exclusion criteria: 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. Subjects who were previously treated with an interferon and ribavirin regimen or HCV direct acting anti-viral regimen. 4. Prior attempt to treat hepatitis C with any investigational medication or herbal product. 5. 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). 6. Subject has participated/is currently participating or intention to participate in another clinical trial with an investigational compound within 30 days at the screening visit. 7. Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. 8. Subject has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC. 9. 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. 10. Subject has pre-existing psychiatric conditions 11. Subject has a clinical diagnosis of substance abuse. 12. Subject has any known medical condition that could interfere with the subject’s participation in and completion of the trial 13. Subject has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years. Subjects under evaluation for malignancy are not eligible. 14. 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 15. Subject is a member or a family member of the investigational study staff or sponsor staff directly involved with this study. 16. Subject has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the efficacy of the two boceprevir (BOC) containing therapeutic regimens using non-inferiority in treatment naïve subjects with chronic hepatitis C genotype 1 who have the IL28B CC allele. The regimens differ in the treatment for subjects who achieve HCV RNA undetectability at the end of the Peginterferon Alfa-2a /ribavirin (PEG2a/R) 4 week lead-in. The primary endpoint of this study is sustained virologic response (SVR) defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. ; Secondary Objective: To estimate the difference in the SVR rate in subjects who have undetectable HCV RNA at TW4 (rapid virologic response, RVR) in Arm 2a compared to Arm 1a. These subjects receive 4 weeks of PEG2a/R and then: 1) Arm 1a: an additional 20 weeks of PEG2a/R for a 24 week regimen. 2) Arm 2a: an additional 20 weeks of therapy with BOC plus PEG2a/R for a 24 week regimen. ;Primary end point(s): The Primary Efficacy Endpoint is the achievement of SVR, defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24 in all randomized subjects in two boceprevir containing therapeutic regimens arm 2 compared to arm 1 of a subject is missing HCV-RNA at FW24 window but has data available after FW24 will be used for the SVR evaluation. If a subject is missing data at and after FW 24 window and has undetectable HCV-RNA at FW 12, the subject will be considered a sustained virologic responder.;Timepoint(s) of evaluation of this end point: HCV-RNA at Follow-up Week (FW) 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Key Secondary Efficacy Endpoint is the achievement of SVR defined as undetectable HCV-RNA at FW 24 in randomized subjects who are HCV-RNA undetectable at TW 4 (RVR) and are assigned shorter treatment duration PEG2a/R for additional 20 weeks (Arm 1a) or BOC + PEG2a/R 20 weeks (Arm 2a). Other Secondary Efficacy Endpoints: • The achievement of SVR12 defined as undetectable HCV-RNA at FW 12 in subjects in Arm 2 compared to Arm 1. • The achievement of SVR12 defined as undetectable HCV-RNA at FW 12 in subjects who are HCV-RNA undetectable at TW 4, Arm 2a compared to Arm 1a • The proportion of subjects with undetectable HCV-RNA at TW 4 in each Arm (1, 2) • The proportion of subjects with an undetectable HCV RNA at TW 8, TW 12 for Arm 1a, and 4 and 8 weeks after the addition of Boceprevir in Arm 2 (2a and 2b) and Arm 1b, • The SVR rates in subjects with an undetectable HCV RNA at TW 8 or TW 12 for Arm 1a, 2a and 2b, and at TW 10 or TW 14 for Arm 1b. • The proportion of subjects in each Arm (1 and 2) and subarms (1a, 1b, 2a, 2b) who relapse as defined as having undetectable HCV RNA at the end of therapy with detectable HCV RNA in the follow-up period (post-treatment) • Change from baseline in the log10 HCV RNA at TW 4, and SVR by log change from baseline at TW 4 • The proportion of subjects with HCV virologic breakthrough • The proportion of subjects with incomplete virologic response/rebound ; Timepoint(s) of evaluation of this end point: For key secondary end point: HCV-RNA at Follow-up Week (FW) 24 Other Secondary Efficacy Endpoints: HCV-RNA at Follow-up Week (FW) 12 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Estonia, Finland, France, Germany, Guatemala, Hong Kong, Hungary, India, Israel, Korea, Republic of, Lithuania, Malaysia, Mexico, New Zealand, Peru, Philippines, Poland, Portugal, Puerto Rico, Russian Federation, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States, Venezuela, Bolivarian Republic of
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp, a Subsidiary of Merck & Co., Inc.
Outcome results
None listed