Clinical trial NCT01309932: Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin
Official title: A Phase 2B, Randomized Study to Evaluate the Safety and Efficacy of Pegylated Interferon Lambda (BMS-914143) Administered With Ribavirin Plus a Single Direct Antiviral Agent (BMS-790052 or BMS-650032) Versus Pegasys Administered With Ribavirin (Part A) and of Pegylated Interferon Lambda (BMS-914143) Administered With or Without Ribavirin Plus 2 Direct Antiviral Agents (BMS-790052 and BMS-650032) (Part B) in Chronic Hepatitis C Genotype-1 Treatment naïve Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-03-07
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if combination therapy with Pegylated Interferon Lambda (BMS-914143) plus Ribavirin (RBV) with a single direct antiviral agent (BMS-790052 or BMS-650032) for 24 weeks is effective and safe for treatment of Chronic Hepatitis C (CHC) compared to current standard therapy with Pegylated Interferon Alpha-2a plus RBV for 48 weeks.

Detailed description: Study Classification: Pharmacokinetics/ Pharmacodynamics

Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

* Chronic Hepatitis C, Genotype 1
* HCV RNA \>100,000 IU/mL at screening;
* Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg);
* Liver biopsy within prior 2 years; subjects with compensated cirrhosis can enroll and will be capped at approximately 10%

Exclusion Criteria:

* Any evidence of liver disease other than HCV;
* Co-infection with HIV;
* Diagnosed or suspected hepatocellular carcinoma;
* Medical history or laboratory value abnormalities that would prohibit the use of Pegylated Interferon Alpha-2a or Ribavirin

Primary outcomes:
measure: Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs)
timeFrame: Up to end of treatment ( maximum of 48 weeks) plus 30 days
measure: Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)
timeFrame: At end of treatment (maximum of 48 weeks)
measure: Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)
timeFrame: Post-treatment Week 24
Secondary outcomes:
measure: Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B
timeFrame: Weeks 4, Weeks 12 and post-treatment Weeks 24
measure: Proportion of subjects with either a 2-log or greater decrease in Hepatitis C virus (HCV) Ribonucleic acid (RNA) levels from baseline or undetectable levels of HCV RNA
timeFrame: Weeks 2, Weeks 4 and Weeks 12
measure: Proportion of subjects with viral breakthrough, defined as confirmed > 1 log10 increase in HCV RNA over nadir or confirmed HCV RNA ≥ Lower limit of quantitation (LLOQ) after confirmed undetectable HCV RNA while on treatment
timeFrame: Post-treatment Week 48
measure: Proportion of subjects with undetectable HCV RNA at the end of treatment that develop detectable levels of HCV RNA in the post-treatment follow-up period
timeFrame: Post-treatment Week 48
measure: Serum HCV Ribonucleic acid (RNA) levels over time
timeFrame: Days 1, 3, Weeks 1, 2, 4, 6, 8, 12, 16, 20, and end of treatment (Week 16, 24 or 48 depending on treatment assignment)
measure: Proportion of subjects with undetectable HCV RNA over time
timeFrame: Days 1, 3, Weeks 1, 2, 4, 6, 8, 12, 16, 20, and end of treatment (Week 16, 24 or 48 depending on treatment assignment)
measure: Time to viral clearance, defined as an absence of detectable HCV RNA
timeFrame: Day 1, 3, Week 1, 2, 4, 6, 8, 12, 24, 36, end of treatment (Week 48), Post-Treatment at Week 4, 12, 24, 36, 48, and 56
measure: Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Maximum observed serum/plasma concentration (Cmax)
timeFrame: Cmax will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
measure: Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Time to maximum concentration (Tmax)
timeFrame: Tmax will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
measure: Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Minimal observed serum/plasma concentration (Cmin)
timeFrame: Cmin will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
measure: Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Area under the serum/plasma concentration-time curve during one dose interval AUC(TAU)
timeFrame: AUC(TAU) will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
measure: Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In all subjects, trough concentrations will be assessed (Ctrough)
timeFrame: Troughs at baseline (week 0), weeks 2, 4, 8, 12, 16, and 24
measure: Proportion of subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA
timeFrame: At end of treatment (maximum of 48 weeks) and follow-up Week 12
measure: Proportion of subjects with 4-week sustained virologic response (SVR4), defined as undetectable HCV RNA
timeFrame: At end of treatment (maximum of 48 weeks) and follow-up Week 4
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Palm Springs
country: United States
facility: Desert Medical Group Inc.
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver And Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Lutherville
country: United States
facility: Johns Hopkins University
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Manhasset
country: United States
facility: Bristol-Myers Squibb/David E. Bernstein, Md
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Statesville
country: United States
facility: Carolinas Center For Liver Disease
state: North Carolina
city: Houston
country: United States
facility: St. Luke'S Episcopal Hospital - Baylor College Of Medicine
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Clayton Vic
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Clichy Cedex
country: France
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Pisa
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Hiroshima-shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Kawasaki-shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Osaka-shi
country: Japan
facility: Local Institution
state: Osaka
city: Iruma-gun
country: Japan
facility: Local Institution
state: Saitama
city: Minato-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Musashino-shi
country: Japan
facility: Local Institution
state: Tokyo
city: Grafton
country: New Zealand
facility: Local Institution
state: Auckland
city: Christchurch
country: New Zealand
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Fundacion De Investigacion De Diego
city: Barcelona
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: