Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin

Phase 2

Completed

• Conditions: Hepatitis C
• Interventions: Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: BMS-790052 (NS5A Inhibitor); Biological: Pegylated Interferon Alfa-2a (pegIFNα-2a); Drug: Ribavirin (RBV); Drug: BMS-650032 (NS3 Protease Inhibitor); Drug: Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor); Drug: Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor); Drug: Placebo for Ribavirin (RBV)

• Registration Number: NCT01309932
• Lead Sponsor: Bristol-Myers Squibb

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

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-04
• Study First Submitted QC: 2011-03-04
• Study First Posted: 2011-03-07
• Primary Completion: 2014-07
• Study Completion: 2014-09
• Status Verified: 2015-09
• Disposition First Submitted: 2015-09-23
• Disposition First Submitted QC: 2015-09-23
• Last Update Submitted: 2015-09-23
• Disposition First Posted: 2015-10-09
• Last Update Posted: 2015-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 165

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%

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin	Pegylated Interferon Lambda (pegIFNλ)	Part A
A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin	BMS-790052 (NS5A Inhibitor)	Part A
A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin	Ribavirin (RBV)	Part A
A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin	Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor)	Part A
A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin	Pegylated Interferon Lambda (pegIFNλ)	Part A
A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin	BMS-650032 (NS3 Protease Inhibitor)	Part A
A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin	Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)	Part A
A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV	Pegylated Interferon Alfa-2a (pegIFNα-2a)	Part A
A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks)	BMS-790052 (NS5A Inhibitor)	Part B
A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV	Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)	Part A
A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV	Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor)	Part A
A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks)	BMS-650032 (NS3 Protease Inhibitor)	Part B
A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks)	Pegylated Interferon Lambda (pegIFNλ)	Part B
A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks)	Pegylated Interferon Lambda (pegIFNλ)	Part B
A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks)	BMS-650032 (NS3 Protease Inhibitor)	Part B
A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)	BMS-650032 (NS3 Protease Inhibitor)	Part B
A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)	Pegylated Interferon Lambda (pegIFNλ)	Part B
A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)	Placebo for Ribavirin (RBV)	Part B
A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks)	Placebo for Ribavirin (RBV)	Part B
A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks)	BMS-650032 (NS3 Protease Inhibitor)	Part B
A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks)	Pegylated Interferon Lambda (pegIFNλ)	Part B
A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin	Ribavirin (RBV)	Part A
A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks)	BMS-790052 (NS5A Inhibitor)	Part B
A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks)	Ribavirin (RBV)	Part B
A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks)	Ribavirin (RBV)	Part B
A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)	BMS-790052 (NS5A Inhibitor)	Part B
A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks)	BMS-790052 (NS5A Inhibitor)	Part B
A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV	Ribavirin (RBV)	Part A

Primary Outcome Measures

Name	Time	Method
Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs)	Up to end of treatment ( maximum of 48 weeks) plus 30 days
Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)	Post-treatment Week 24

Secondary Outcome Measures

Name	Time	Method
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	Weeks 2, Weeks 4 and Weeks 12
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	Post-treatment Week 48
Time to viral clearance, defined as an absence of detectable HCV RNA	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
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)	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)
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)	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)
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)	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)
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)	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)
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)	Troughs at baseline (week 0), weeks 2, 4, 8, 12, 16, and 24
Proportion of subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA	At end of treatment (maximum of 48 weeks) and follow-up Week 12
Proportion of subjects with 4-week sustained virologic response (SVR4), defined as undetectable HCV RNA	At end of treatment (maximum of 48 weeks) and follow-up Week 4
Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B	Weeks 4, Weeks 12 and post-treatment Weeks 24	* Part A PDR is defined as HCV RNA at Week 4 \< LLOQ and Week 12 undetectable; * Part B PDR is defined as HCV RNA at Week 2 ≥ 2 log10 decrease (or \< Lower limit of quantitation (LLOQ) if baseline HCV RNA \< 2400 IU/mL), Week 4 \< LLOQ and Week 12 undetectable
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	Post-treatment Week 48
Serum HCV Ribonucleic acid (RNA) levels over time	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)
Proportion of subjects with undetectable HCV RNA over time	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)

Trial Locations

Locations (15)

Johns Hopkins University; 🇺🇸 Lutherville, Maryland, United States

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Desert Medical Group Inc.; 🇺🇸 Palm Springs, California, United States

Local Institution; 🇪🇸 Valencia, Spain

Fundacion De Investigacion De Diego; 🇵🇷 San Juan, Puerto Rico

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

University Of Colorado Denver And Hospital; 🇺🇸 Aurora, Colorado, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Bristol-Myers Squibb/David E. Bernstein, Md; 🇺🇸 Manhasset, New York, United States

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

Yale University School Of Medicine; 🇺🇸 New Haven, Connecticut, United States

St. Luke'S Episcopal Hospital - Baylor College Of Medicine; 🇺🇸 Houston, Texas, United States

Carolinas Center For Liver Disease; 🇺🇸 Statesville, North Carolina, United States

Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Metropolitan Research; 🇺🇸 Fairfax, Virginia, United States