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

Hepatitis C Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01309932
• Other study ID #: AI452-008
• Secondary ID: 2010-022568-11
• Status: Completed
• Phase: Phase 2
• First received: March 4, 2011
• Last updated: September 23, 2015
• Start date: March 2011
• Est. completion date: September 2014

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: National Health and Medical Research CouncilNew Zealand: MedsafeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthItaly: National Bioethics CommitteeItaly: National Institute of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines AgencySpain: Agencia Española de Medicamentos y Productos SanitariosJapan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Description:

Study Classification: Pharmacokinetics/ Pharmacodynamics

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: September 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

Biological:
• Pegylated Interferon Lambda (pegIFN?)
Solution, Subcutaneous, 180 µg/mL, Once weekly, 24 or 48 weeks depending on response

Drug:
• BMS-790052 (NS5A Inhibitor)
Tablets, Oral, 60 mg, Once daily, 24 weeks
• Ribavirin (RBV)
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks
• BMS-650032 (NS3 Protease Inhibitor)
Tablets, Oral, 200 mg, Twice daily, 24 weeks

Biological:
• Pegylated Interferon Alfa-2a (pegIFNa-2a)
Solution, Subcutaneous, 180 µg/mL, Once weekly, 48 weeks
• Pegylated Interferon Lambda (pegIFN?)
Solution, Subcutaneous, 180 µg/mL, Once weekly, 24 weeks

Drug:
• Ribavirin (RBV)
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 24 weeks

Biological:
• Pegylated Interferon Lambda (pegIFN?)
Solution, Subcutaneous, 180 µg/mL, Once weekly, 16 weeks

Drug:
• Ribavirin (RBV)
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 16 weeks
• BMS-790052 (NS5A Inhibitor)
Tablets, Oral, 60 mg, Once daily, 16 weeks
• BMS-650032 (NS3 Protease Inhibitor)
Tablets, Oral, 200 mg, Twice daily, 16 weeks
• Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor)
Tablets, Oral, 0 mg, Twice daily, 24 weeks
• Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)
Tablets, Oral, 0 mg, Once daily, 24 weeks
• Placebo for Ribavirin (RBV)
Tablets, Oral, 0 mg, Twice daily, 24 weeks
• Placebo for Ribavirin (RBV)
Tablets, Oral, 0 mg, Twice daily, 16 weeks

Locations

Country	Name	City	State
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Clayton Vic	Victoria
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Perth	Western Australia
France	Local Institution	Clichy Cedex
France	Local Institution	Creteil
France	Local Institution	Montpellier Cedex 5
France	Local Institution	Nice Cedex 03
France	Local Institution	Paris Cedex 12
France	Local Institution	Paris Cedex 14
Germany	Local Institution	Essen
Germany	Local Institution	Frankfurt
Germany	Local Institution	Hamburg
Italy	Local Institution	Pisa
Italy	Local Institution	Roma
Japan	Local Institution	Hiroshima-shi	Hiroshima
Japan	Local Institution	Iruma-gun	Saitama
Japan	Local Institution	Kawasaki-shi	Kanagawa
Japan	Local Institution	Minato-ku	Tokyo
Japan	Local Institution	Musashino-shi	Tokyo
Japan	Local Institution	Osaka-shi	Osaka
Japan	Local Institution	Sapporo-shi	Hokkaido
New Zealand	Local Institution	Christchurch
New Zealand	Local Institution	Grafton	Auckland
Puerto Rico	Fundacion De Investigacion De Diego	San Juan
Spain	Local Institution	Barcelona
Spain	Local Institution	Valencia
United States	University Of Colorado Denver And Hospital	Aurora	Colorado
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Henry Ford Health System	Detroit	Michigan
United States	Metropolitan Research	Fairfax	Virginia
United States	St. Luke'S Episcopal Hospital - Baylor College Of Medicine	Houston	Texas
United States	Johns Hopkins University	Lutherville	Maryland
United States	Bristol-Myers Squibb/David E. Bernstein, Md	Manhasset	New York
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Desert Medical Group Inc.	Palm Springs	California
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Texas Liver Institute	San Antonio	Texas
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Carolinas Center For Liver Disease	Statesville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Japan,  New Zealand,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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)	Yes
Primary	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	Yes
Secondary	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	Weeks 4, Weeks 12 and post-treatment Weeks 24	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	Serum levels of pegIFN? and pegIFNa-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 pegIFN? and pegIFNa-2a)	No
Secondary	Serum levels of pegIFN? and pegIFNa-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 pegIFN? and pegIFNa-2a)	No
Secondary	Serum levels of pegIFN? and pegIFNa-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 pegIFN? and pegIFNa-2a)	No
Secondary	Serum levels of pegIFN? and pegIFNa-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 pegIFN? and pegIFNa-2a)	No
Secondary	Serum levels of pegIFN? and pegIFNa-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	No
Secondary	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	No
Secondary	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	No

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