Hepatitis C
Parallel, open-label, randomized, multiple-dose study to evaluate the safety, pharmacokinetics and pharmacodynamics of BMS-790052 and BMS-650032 in combination in null responders to standard of care infected with chronic hepatitis C virus genotype 1
Background:
HCV genotype 1 null responders respond poorly to re-treatment with peginterferon (peg-IFN) and ribavirin (RBV). Even triple therapy of telaprevir (NS3 or protease inhibitor), peg-IFN and RBV yields only 30% SVR rate in this difficult to treat population. Combination of direct-acting antivirals (DAAs) may be needed for these patients.
BMS-790052 is an HCV NS5A replication complex inhibitor and BMS-650032 is an HCV NS3 protease inhibitor.
Results of part 1 of this study were presented at EASL meeting (European Association for the Study of the Liver) on April 2, 2011. In brief, 4/11 (2/2 genotype 1b and 2/9 genotype 1a) patients who received 2DAAs alone (BMS-790052 and BMS-650032) achieved SVR24 and 9/10 patients who received these 2 DAAs+peg-IFN+RBV achieved SVR24.Enrollment Status:
- Part 1 – Closed for enrollment
- Part 2 – Anticipated to open for enrollment in May 2010, IRB approved
Primary efficacy endpoint:
Undetectable HCV RNA 12 weeks after end of treatment (SVR12)
Main Inclusion Criteria
- HCV genotype 1 patients who are null responders, defined as subjects who after at least 12 weeks of therapy with the current standard of care have never attained ≥ 2 log10 (100-fold) drop in HCV RNA level
- HCV RNA viral load of ≥ 100,000 IU/mL at screening
- Ages 18–70 years.
Main Exclusion Criteria
- Cirrhosis
- Other major medical problems
- Subjects who previously did not tolerate interferon or ribavirin therapy
- Current or known history of cancer.
Study design - Part 2
Arm A – Genotype 1b patients only, 2 DAAs only x 24 weeks
Arm A1: BMS-790052 60 mg QD + BMS-650032 200 mg BID
Arm A2: BMS-790052 60 mg QD + BMS-650032 200 mg QD
Arm B – Genotype 1a and 1b, 2 DAAs + peg-IFN and RBV
Arm B1: BMS-790052 60 mg QD + BMS-650032 200 mg BID + peg-IFN and RBV
Arm B2: BMS-790052 60 mg QD + BMS-650032 200 mg QD + peg-IFN and RBV
Arm B3: BMS-790052 60 mg QD + BMS-650032 200 mg BID + Ribavirin (this arm will be deferred subject to responses in arm A)
Patients will be monitored very closely (daily for the first week and three times in the second week) then every 1–4 weeks to evaluate side effects and viral response.
Costs for the Patient
All study-related tests, procedures, and study-related medications will be covered by the sponsor and provided free of charge to the patient. Subjects will be reimbursed $100 (regular visit) and $200 (for longer visit with PK blood draw) for each completed study visit to offset travel expenses.
Contact persons
Diane White - Study Coordinator (734) 763-6647, Fax: 734-615-1112 (dfwhite@med.umich.edu)
Anna Lok, MD - Principal Investigator aslok@med.umich.edu
A phase 3, safety and efficacy study of boceprevir in previously untreated subjects with chronic hepatitis C virus genotype 1
Enrollment Status: Closed for enrollment; patients will continue to be followed in long-term follow-up study
Primary aim
To compare the efficacy of boceprevir in combination with standard of care (Pegintron + ribavirin) and standard of care alone in previously untreated patients with hepatitis C virus genotype 1.
Sponsor
Schering Plough (Merck)
Contact persons
Diane White - Study Coordinator (734) 763-6647, Fax: 734-615-1112 (dfwhite@med.umich.edu)
Anna Lok, MD - Principal Investigator aslok@med.umich.edu
A randomized, partially blinded study to evaluate the safety, tolerability and effect on virological response of treatment with the HCV protease inhibitor RO5190591 in combination with Pegasys and Copegus for 12 weeks, versus treatment with Pegasys and Copegus alone, in treatment-naïve patients with chronic hepatitis C genotype 1 virus infection
Enrollment Status: Closed for enrollment; patients will continue to be followed in long-term follow-up study
Primary aim
To evaluate the safety, tolerability, and effect on virological response of a 12-week duration of RO5190591 in combination with Pegasys and Copegus compared to the combination of Pegasys and Copegus alone in treatment naïve patients with chronic hepatitis C genotype 1 virus infection.
Sponsor
Hoffmann-La Roche
Contact persons
Diane White - Study Coordinator (734) 763-6647, Fax: 734-615-1112 (dfwhite@med.umich.edu)
Anna Lok, MD - Principal Investigator aslok@med.umich.edu
Hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial
Enrollment Status: Study is closed.
Primary aim
To determine whether low dose maintenance pegylated interferon will prevent disease progression in patients with advanced hepatitis C who failed to respond to combination therapy with pegylated interferon and ribavirin.
Sponsor
National Institutes of Health
Results of this study have been published in approximately 50 papers. See www.haltctrial.org for information about this study. Data analyses still ongoing.
Contact person
Anna Lok, MD - Principal Investigator aslok@med.umich.edu
