Back to results

Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin (D-LITE)

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Pegylated Interferon Lambda (pegIFNλ)

BMS-790052 (NS5A Inhibitor)

Ribavirin (RBV)

BMS-650032 (NS3 Protease Inhibitor)

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

Pegylated Interferon Lambda (pegIFNλ)

Ribavirin (RBV)

Pegylated Interferon Lambda (pegIFNλ)

Ribavirin (RBV)

BMS-790052 (NS5A Inhibitor)

BMS-650032 (NS3 Protease Inhibitor)

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

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

Placebo for Ribavirin (RBV)

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

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

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

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

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

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

Arm Description

Part A

Part B

Outcomes

Primary Outcome Measures

Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs)

Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)

Secondary Outcome Measures

Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B

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 either a 2-log or greater decrease in Hepatitis C virus (HCV) Ribonucleic acid (RNA) levels from baseline or undetectable levels of HCV RNA

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

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

Serum HCV Ribonucleic acid (RNA) levels over time

Proportion of subjects with undetectable HCV RNA over time

Time to viral clearance, defined as an absence of detectable HCV RNA

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)

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)

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)

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)

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)

Proportion of subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA

Proportion of subjects with 4-week sustained virologic response (SVR4), defined as undetectable HCV RNA

Full Information

NCT ID

NCT01309932

First Posted

March 4, 2011

Last Updated

September 23, 2015

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01309932

Brief Title

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

Acronym

D-LITE

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

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

March 2011 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

165 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Part A

Arm Title

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

Arm Type

Experimental

Arm Description

Part A

Arm Title

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

Arm Type

Active Comparator

Arm Description

Part A

Arm Title

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

Arm Type

Experimental

Arm Description

Part B

Arm Title

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

Arm Type

Experimental

Arm Description

Part B

Arm Title

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

Arm Type

Experimental

Arm Description

Part B

Arm Title

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

Arm Type

Experimental

Arm Description

Part B

Intervention Type

Biological

Intervention Name(s)

Pegylated Interferon Lambda (pegIFNλ)

Other Intervention Name(s)

BMS-914143

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

BMS-790052 (NS5A Inhibitor)

Other Intervention Name(s)

BMS-790052

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ribavirin (RBV)

Other Intervention Name(s)

Ribasphere

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

BMS-650032 (NS3 Protease Inhibitor)

Other Intervention Name(s)

BMS-650032

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

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

Other Intervention Name(s)

Pegasys®

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Pegylated Interferon Lambda (pegIFNλ)

Other Intervention Name(s)

BMS-914143

Intervention Description

Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 weeks

Intervention Type

Drug

Intervention Name(s)

Ribavirin (RBV)

Other Intervention Name(s)

Ribasphere

Intervention Description

Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 24 weeks

Intervention Type

Biological

Intervention Name(s)

Pegylated Interferon Lambda (pegIFNλ)

Other Intervention Name(s)

BMS-914143

Intervention Description

Solution, Subcutaneous, 180 μg/mL, Once weekly, 16 weeks

Intervention Type

Drug

Intervention Name(s)

Ribavirin (RBV)

Other Intervention Name(s)

Ribasphere

Intervention Description

Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 16 weeks

Intervention Type

Drug

Intervention Name(s)

BMS-790052 (NS5A Inhibitor)

Other Intervention Name(s)

BMS-790052

Intervention Description

Tablets, Oral, 60 mg, Once daily, 16 weeks

Intervention Type

Drug

Intervention Name(s)

BMS-650032 (NS3 Protease Inhibitor)

Other Intervention Name(s)

BMS-650032

Intervention Description

Tablets, Oral, 200 mg, Twice daily, 16 weeks

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

Placebo for BMS-650032

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

Placebo for BMS-790052

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo for Ribavirin (RBV)

Other Intervention Name(s)

Placebo for Ribasphere

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo for Ribavirin (RBV)

Other Intervention Name(s)

Placebo for Ribasphere

Intervention Description

Tablets, Oral, 0 mg, Twice daily, 16 weeks

Primary Outcome Measure Information:

Title

Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs)

Time Frame

Up to end of treatment ( maximum of 48 weeks) plus 30 days

Title

Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)

Time Frame

At end of treatment (maximum of 48 weeks)

Title

Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)

Time Frame

Post-treatment Week 24

Secondary Outcome Measure Information:

Title

Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B

Description

Time Frame

Weeks 4, Weeks 12 and post-treatment Weeks 24

Title

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

Time Frame

Weeks 2, Weeks 4 and Weeks 12

Title

Time Frame

Post-treatment Week 48

Title

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

Time Frame

Post-treatment Week 48

Title

Serum HCV Ribonucleic acid (RNA) levels over time

Time Frame

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)

Title

Proportion of subjects with undetectable HCV RNA over time

Time Frame

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)

Title

Time to viral clearance, defined as an absence of detectable HCV RNA

Time Frame

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

Title

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)

Time Frame

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)

Title

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)

Time Frame

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)

Title

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)

Time Frame

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)

Title

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)

Time Frame

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)

Title

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)

Time Frame

Troughs at baseline (week 0), weeks 2, 4, 8, 12, 16, and 24

Title

Proportion of subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA

Time Frame

At end of treatment (maximum of 48 weeks) and follow-up Week 12

Title

Proportion of subjects with 4-week sustained virologic response (SVR4), defined as undetectable HCV RNA

Time Frame

At end of treatment (maximum of 48 weeks) and follow-up Week 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Mayo Clinic Hospital

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85054

Country

United States

Facility Name

Desert Medical Group Inc.

City

Palm Springs

State/Province

California

ZIP/Postal Code

92262

Country

United States

Facility Name

University Of Colorado Denver And Hospital

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Yale University School Of Medicine

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

Facility Name

Johns Hopkins University

City

Lutherville

State/Province

Maryland

ZIP/Postal Code

21093

Country

United States

Facility Name

Henry Ford Health System

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Bristol-Myers Squibb/David E. Bernstein, Md

City

Manhasset

State/Province

New York

ZIP/Postal Code

11030

Country

United States

Facility Name

Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28203

Country

United States

Facility Name

Carolinas Center For Liver Disease

City

Statesville

State/Province

North Carolina

ZIP/Postal Code

28677

Country

United States

Facility Name

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

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Texas Liver Institute

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

Facility Name

Metropolitan Research

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Virginia Mason Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98101

Country

United States

Facility Name

Local Institution

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

Local Institution

City

Clayton Vic

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Facility Name

Local Institution

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

Local Institution

City

Perth

State/Province

Western Australia

ZIP/Postal Code

6001

Country

Australia

Facility Name

Local Institution

City

Clichy Cedex

ZIP/Postal Code

92118

Country

France

Facility Name

Local Institution

City

Creteil

ZIP/Postal Code

94000

Country

France

Facility Name

Local Institution

City

Montpellier Cedex 5

ZIP/Postal Code

34295

Country

France

Facility Name

Local Institution

City

Nice Cedex 03

ZIP/Postal Code

06202

Country

France

Facility Name

Local Institution

City

Paris Cedex 12

ZIP/Postal Code

75571

Country

France

Facility Name

Local Institution

City

Paris Cedex 14

ZIP/Postal Code

75679

Country

France

Facility Name

Local Institution

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Local Institution

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

Local Institution

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Local Institution

City

Pisa

ZIP/Postal Code

56124

Country

Italy

Facility Name

Local Institution

City

Roma

ZIP/Postal Code

00161

Country

Italy

Facility Name

Local Institution

City

Hiroshima-shi

State/Province

Hiroshima

ZIP/Postal Code

7348511

Country

Japan

Facility Name

Local Institution

City

Sapporo-shi

State/Province

Hokkaido

ZIP/Postal Code

060-0033

Country

Japan

Facility Name

Local Institution

City

Kawasaki-shi

State/Province

Kanagawa

ZIP/Postal Code

2138587

Country

Japan

Facility Name

Local Institution

City

Osaka-shi

State/Province

Osaka

ZIP/Postal Code

5458586

Country

Japan

Facility Name

Local Institution

City

Iruma-gun

State/Province

Saitama

ZIP/Postal Code

3500495

Country

Japan

Facility Name

Local Institution

City

Minato-ku

State/Province

Tokyo

ZIP/Postal Code

105-0001

Country

Japan

Facility Name

Local Institution

City

Musashino-shi

State/Province

Tokyo

ZIP/Postal Code

180-0023

Country

Japan

Facility Name

Local Institution

City

Grafton

State/Province

Auckland

ZIP/Postal Code

1010

Country

New Zealand

Facility Name

Local Institution

City

Christchurch

ZIP/Postal Code

8011

Country

New Zealand

Facility Name

Fundacion De Investigacion De Diego

City

San Juan

ZIP/Postal Code

00927

Country

Puerto Rico

Facility Name

Local Institution

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

Facility Name

Local Institution

City

Valencia

ZIP/Postal Code

46010

Country

Spain

12. IPD Sharing Statement

Links:

URL

http://www.bms.com/studyconnect/Pages/home.aspx

Description

BMS clinical trial educational resource

Learn more about this trial

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

We'll reach out to this number within 24 hrs

Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin (D-LITE)

Hepatitis C

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial