Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C	Biological: Pegylated Interferon Lambda (pegIFNλ) Drug: BMS-790052 (NS5A Inhibitor) Drug: Ribavirin (RBV) Drug: BMS-650032 (NS3 Protease Inhibitor) 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) Drug: Placebo for Ribavirin (RBV)	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Interferon Alfa-2a Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

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) [ Time Frame: Up to end of treatment ( maximum of 48 weeks) plus 30 days ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B [ Time Frame: Weeks 4, Weeks 12 and post-treatment Weeks 24 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Weeks 2, Weeks 4 and Weeks 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Post-treatment Week 48 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	189
Study Start Date:	March 2011
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A1: pegIFNλ+BMS-790052+Placebo for BMS-650032+Ribavirin Part A	Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 or 48 weeks depending on response Other Name: BMS-914143 Drug: BMS-790052 (NS5A Inhibitor) Tablets, Oral, 60 mg, Once daily, 24 weeks Other Name: BMS-790052 Drug: Ribavirin (RBV) Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks Other Name: Ribasphere Drug: Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor) Tablets, Oral, 0 mg, Twice daily, 24 weeks Other Name: Placebo for BMS-650032
Experimental: A2: pegIFNλ+BMS-650032+Placebo for BMS-790052+Ribavirin Part A	Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 or 48 weeks depending on response Other Name: BMS-914143 Drug: Ribavirin (RBV) Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks Other Name: Ribasphere Drug: BMS-650032 (NS3 Protease Inhibitor) Tablets, Oral, 200 mg, Twice daily, 24 weeks Other Name: BMS-650032 Drug: Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor) Tablets, Oral, 0 mg, Once daily, 24 weeks Other Name: Placebo for BMS-790052
Active Comparator: A3: pegIFNα-2a+PBO for BMS-790052+PBO for BMS-650032+RBV Part A	Drug: Ribavirin (RBV) Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks Other Name: Ribasphere Biological: Pegylated Interferon Alfa-2a (pegIFNα-2a) Solution, Subcutaneous, 180 μg/mL, Once weekly, 48 weeks Other Name: Pegasys® Drug: Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor) Tablets, Oral, 0 mg, Twice daily, 24 weeks Other Name: Placebo for BMS-650032 Drug: Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor) Tablets, Oral, 0 mg, Once daily, 24 weeks Other Name: Placebo for BMS-790052
Experimental: A4: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (24 weeks) Part B	Drug: BMS-790052 (NS5A Inhibitor) Tablets, Oral, 60 mg, Once daily, 24 weeks Other Name: BMS-790052 Drug: BMS-650032 (NS3 Protease Inhibitor) Tablets, Oral, 200 mg, Twice daily, 24 weeks Other Name: BMS-650032 Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 weeks Other Name: BMS-914143 Drug: Ribavirin (RBV) Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 24 weeks Other Name: Ribasphere
Experimental: A5: pegIFNλ+BMS-790052+BMS-650032+Ribavirin (16 weeks) Part B	Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 16 weeks Other Name: BMS-914143 Drug: Ribavirin (RBV) Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 16 weeks Other Name: Ribasphere Drug: BMS-790052 (NS5A Inhibitor) Tablets, Oral, 60 mg, Once daily, 16 weeks Other Name: BMS-790052 Drug: BMS-650032 (NS3 Protease Inhibitor) Tablets, Oral, 200 mg, Twice daily, 16 weeks Other Name: BMS-650032
Experimental: A6: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (24 weeks) Part B	Drug: BMS-790052 (NS5A Inhibitor) Tablets, Oral, 60 mg, Once daily, 24 weeks Other Name: BMS-790052 Drug: BMS-650032 (NS3 Protease Inhibitor) Tablets, Oral, 200 mg, Twice daily, 24 weeks Other Name: BMS-650032 Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 weeks Other Name: BMS-914143 Drug: Placebo for Ribavirin (RBV) Tablets, Oral, 0 mg, Twice daily, 24 weeks Other Name: Placebo for Ribasphere
Experimental: A7: pegIFNλ+BMS-790052+BMS-650032+Placebo for RBV (16 weeks) Part B	Biological: Pegylated Interferon Lambda (pegIFNλ) Solution, Subcutaneous, 180 μg/mL, Once weekly, 16 weeks Other Name: BMS-914143 Drug: BMS-790052 (NS5A Inhibitor) Tablets, Oral, 60 mg, Once daily, 16 weeks Other Name: BMS-790052 Drug: BMS-650032 (NS3 Protease Inhibitor) Tablets, Oral, 200 mg, Twice daily, 16 weeks Other Name: BMS-650032 Drug: Placebo for Ribavirin (RBV) Tablets, Oral, 0 mg, Twice daily, 16 weeks Other Name: Placebo for Ribasphere

Detailed Description:

Study Classification: Pharmacokinetics/ Pharmacodynamics

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309932

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Show 38 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01309932 History of Changes
Other Study ID Numbers:	AI452-008, 2010-022568-11
Study First Received:	March 4, 2011
Last Updated:	March 28, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: National Health and Medical Research Council New Zealand: Medsafe France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Ministry of Health Germany: Federal Institute for Drugs and Medical Devices Italy: Ministry of Health Italy: National Bioethics Committee Italy: National Institute of Health Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Italy: The Italian Medicines Agency Spain: Agencia Española de Medicamentos y Productos Sanitarios Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Antiviral Agents
Interferons

Ribavirin
Peginterferon alfa-2a
Protease Inhibitors
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013

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