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

NCT01309932 | Completed Phase 2

• 2 other identifiers: AI452-0082010-022568-11
• Study Type: interventional
• Target: 165
• Locations: 9 countries
• Sites: 40

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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

• 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)

  At end of treatment (maximum of 48 weeks)

• 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 Outcomes (14)

• 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

• 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 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

• 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

• 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)

Study Arms (7)

A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin

EXPERIMENTAL

Part A

Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: BMS-790052 (NS5A Inhibitor); Drug: Ribavirin (RBV); Drug: Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor)

A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin

EXPERIMENTAL

Part A

Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: Ribavirin (RBV); Drug: BMS-650032 (NS3 Protease Inhibitor); Drug: Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)

A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV

ACTIVE COMPARATOR

Part A

Drug: Ribavirin (RBV); Biological: Pegylated Interferon Alfa-2a (pegIFNα-2a); Drug: Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor); Drug: Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)

A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks)

EXPERIMENTAL

Part B

Drug: BMS-790052 (NS5A Inhibitor); Drug: BMS-650032 (NS3 Protease Inhibitor); Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: Ribavirin (RBV)

A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks)

EXPERIMENTAL

Part B

Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: Ribavirin (RBV); Drug: BMS-790052 (NS5A Inhibitor); Drug: BMS-650032 (NS3 Protease Inhibitor)

A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)

EXPERIMENTAL

Part B

Drug: BMS-790052 (NS5A Inhibitor); Drug: BMS-650032 (NS3 Protease Inhibitor); Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: Placebo for Ribavirin (RBV)

A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks)

EXPERIMENTAL

Part B

Biological: Pegylated Interferon Lambda (pegIFNλ); Drug: BMS-790052 (NS5A Inhibitor); Drug: BMS-650032 (NS3 Protease Inhibitor); Drug: Placebo for Ribavirin (RBV)

Interventions

BMS-790052 (NS5A Inhibitor) DRUG

Tablets, Oral, 60 mg, Once daily, 24 weeks

Also known as: BMS-790052

A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin; A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks); A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)

Ribavirin (RBV) DRUG

Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks

Also known as: Ribasphere

A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin; A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin; A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV

BMS-650032 (NS3 Protease Inhibitor) DRUG

Tablets, Oral, 200 mg, Twice daily, 24 weeks

Also known as: BMS-650032

A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin; A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks); A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)

Pegylated Interferon Alfa-2a (pegIFNα-2a) BIOLOGICAL

Solution, Subcutaneous, 180 μg/mL, Once weekly, 48 weeks

Also known as: Pegasys®

A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV

Pegylated Interferon Lambda (pegIFNλ) BIOLOGICAL

Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 or 48 weeks depending on response

Also known as: BMS-914143

A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin; A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin

Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor) DRUG

Tablets, Oral, 0 mg, Twice daily, 24 weeks

Also known as: Placebo for BMS-650032

A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin; A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV

Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor) DRUG

Tablets, Oral, 0 mg, Once daily, 24 weeks

Also known as: Placebo for BMS-790052

A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin; A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV

Placebo for Ribavirin (RBV) DRUG

Tablets, Oral, 0 mg, Twice daily, 24 weeks

Also known as: Placebo for Ribasphere

A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (40)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Desert Medical Group Inc.

Palm Springs, California, 92262, United States

Location

University Of Colorado Denver And Hospital

Aurora, Colorado, 80045, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Bristol-Myers Squibb/David E. Bernstein, Md

Manhasset, New York, 11030, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Carolinas Center For Liver Disease

Statesville, North Carolina, 28677, United States

Location

St. Luke'S Episcopal Hospital - Baylor College Of Medicine

Houston, Texas, 77030, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Metropolitan Research

Fairfax, Virginia, 22031, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Local Institution

Adelaide, South Australia, 5000, Australia

Location

Local Institution

Clayton Vic, Victoria, 3168, Australia

Location

Local Institution

Heidelberg, Victoria, 3084, Australia

Location

Local Institution

Perth, Western Australia, 6001, Australia

Location

Local Institution

Clichy, 92118, France

Location

Local Institution

Créteil, 94000, France

Location

Local Institution

Montpellier, 34295, France

Location

Local Institution

Nice, 06202, France

Location

Local Institution

Paris, 75571, France

Location

Local Institution

Paris, 75679, France

Location

Local Institution

Essen, 45122, Germany

Location

Local Institution

Frankfurt, 60590, Germany

Location

Local Institution

Hamburg, 20246, Germany

Location

Local Institution

Pisa, 56124, Italy

Location

Local Institution

Roma, 00161, Italy

Location

Local Institution

Hiroshima, Hiroshima, 7348511, Japan

Location

Local Institution

Sapporo, Hokkaido, 060-0033, Japan

Location

Local Institution

Kawasaki-shi, Kanagawa, 2138587, Japan

Location

Local Institution

Osaka, Osaka, 5458586, Japan

Location

Local Institution

Iruma-gun, Saitama, 3500495, Japan

Location

Local Institution

Minato-ku, Tokyo, 105-0001, Japan

Location

Local Institution

Musashino-shi, Tokyo, 180-0023, Japan

Location

Local Institution

Grafton, Auckland, 1010, New Zealand

Location

Local Institution

Christchurch, 8011, New Zealand

Location

Fundacion De Investigacion De Diego

San Juan, 00927, Puerto Rico

Location

Local Institution

Barcelona, Barcelona, 08003, Spain

Location

Local Institution

Valencia, 46010, Spain

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis C

Interventions

peginterferon lambda-1a; daclatasvir; Ribavirin; asunaprevir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2011
• First Posted: March 7, 2011
• Study Start: March 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 9, 2015

Record last verified: 2015-09

Locations

DE (3); JP (7); IT (2); PR (1); ES (2); US (13); NZ (2); AU (4); FR (6)