search
Back to results

Study to Determine the Safety and Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) in Patients Who Have Previously Not Received the Standard of Care

Primary Purpose

Chronic Hepatitis C

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PSI-7977
Daclatasvir
Ribavirin
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

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

Inclusion Criteria:

  • Men and women, ages 18 to 70 years.
  • Participants infected with hepatitis C virus (HCV) genotype 1, 2, or 3, with no previous exposure to an interferon formulation (ie, interferon-alpha, pegylated interferon-alpha) ribavirin, or other HCV-specific direct-acting antiviral (including daclatasvir and PSI-7977).
  • Patients should have chronic hepatitis C genotype 1a, 1b, 2, or 3 as documented by: positive test results for anti-HCV antibody; HCV RNA; or a HCV genotype at least 6 months prior to screening, and HCV RNA and anti-HCV antibody at the time of screening.

Exclusion Criteria:

  • Evidence of a medical condition associate with chronic liver disease other than HCV.
  • History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis.
  • History of hemophilia.
  • History of torsade de pointes.
  • Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment.
  • History of gastrointestinal disease or surgical procedure (except cholecystectomy).
  • History of clinically significant cardiac disease.
  • Blood transfusion within 4 weeks prior to study drug administration.
  • Poor venous access.
  • Any other medical, psychiatric, and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation in this study.

Sites / Locations

  • Southern California Liver Centers
  • Research And Education, Inc.
  • University Of Colorado Denver & Hospital
  • University Of Florida Hepatology
  • Orlando Immunology Center
  • Miami Research Associates
  • Mercy Medical Center
  • Johns Hopkins University
  • University Of Michigan Health System
  • Bronx Va Medical Center 3c Sub-J
  • Weill Cornell Medical College
  • Options Health Research, Llc
  • Healthcare Research Consultants
  • University Of Pennsylvania
  • Alamo Medical Research
  • Metropolitan Research
  • Dean Clinic
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Treatment A: PSI-7977 + Daclatasvir

Treatment B: PSI-7977 + Daclatasvir

Treatment C: PSI-7977 + Daclatasvir

Treatment D: PSI-7977 + Daclatasvir

Treatment E: PSI-7977 + Daclatasvir + Ribavirin

Treatment F: PSI-7977 + Daclatasvir+ Ribavirin

Treatment G: PSI-7977 + Daclatasvir

Treatment H: PSI-7977 + BMS-790052 + Ribavirin

Treatment I: PSI-7977 + Daclatasvir

Treatment J: PSI-7977 + Daclatasvir + Ribavirin

Arm Description

Genotype 1a or 1b

Genotype 2 or 3

Genotype 1a or 1b

Genotype 2 or 3

Genotype 1a or 1b

Genotype 2 or 3

Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b

Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b

Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b

Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected (ie, HCV RNA <25 IU/mL) at follow-up Week 12. DCV=daclatasvir, SOF=sofosbuvir.

Secondary Outcome Measures

Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)
SVR24 was defined as participant's hepatitis C virus RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 24. DCV=daclatasvir, SOF=sofosbuvir.
Percentage of Participants With Viral Breakthrough During the Treatment Period
Viral breakthrough is defined as any confirmed increase in viral load ≥1 log from nadir or any confirmed hepatitis C virus RNA levels ≥25 IU/mL on or after Week 8.
Percentage of Participants Who Experienced Viral Relapse During Follow-up Period
Viral relapse during follow-up is defined as any confirmed quantifiable hepatitis C virus (HCV) RNA ≥25 IU/mL with HCV RNA levels less than the lower limit of quantitation, target detected or target not detected, ie, HCV RNA <25 IU/mL at the end of treatment.
Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24
Change from baseline in log10 HCV RNA at scheduled sampling time.
Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe.
Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe

Full Information

First Posted
May 23, 2011
Last Updated
September 23, 2015
Sponsor
Bristol-Myers Squibb
Collaborators
Pharmasset
search

1. Study Identification

Unique Protocol Identification Number
NCT01359644
Brief Title
Study to Determine the Safety and Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) in Patients Who Have Previously Not Received the Standard of Care
Official Title
Parallel, Open-Label, Randomized Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of PSI-7977 in Combination With BMS-790052 With or Without Ribavirin in Treatment Naive Subjects Chronically Infected With Hepatitis C Virus Genotypes 1, 2, or 3
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
Pharmasset

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to determine whether therapy with the combination of PSI-7977 and daclatasvir (BMS-790052) with or without ribavirin is effective in treating hepatitis C virus (HCV) infection when given for 12 or 24 weeks as measured by sustained virologic response with undetectable HCV RNA 12 weeks post treatment

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
350 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Genotype 1a or 1b
Arm Title
Treatment B: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Genotype 2 or 3
Arm Title
Treatment C: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Genotype 1a or 1b
Arm Title
Treatment D: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Genotype 2 or 3
Arm Title
Treatment E: PSI-7977 + Daclatasvir + Ribavirin
Arm Type
Experimental
Arm Description
Genotype 1a or 1b
Arm Title
Treatment F: PSI-7977 + Daclatasvir+ Ribavirin
Arm Type
Experimental
Arm Description
Genotype 2 or 3
Arm Title
Treatment G: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Arm Title
Treatment H: PSI-7977 + BMS-790052 + Ribavirin
Arm Type
Experimental
Arm Description
Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Arm Title
Treatment I: PSI-7977 + Daclatasvir
Arm Type
Experimental
Arm Description
Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Arm Title
Treatment J: PSI-7977 + Daclatasvir + Ribavirin
Arm Type
Experimental
Arm Description
Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Intervention Type
Drug
Intervention Name(s)
PSI-7977
Intervention Description
Tablets, oral, 400 mg, once daily
Intervention Type
Drug
Intervention Name(s)
Daclatasvir
Other Intervention Name(s)
BMS-790052
Intervention Description
Tablets, oral, 60 mg, once daily
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Copegus ®
Intervention Description
Tablets, oral, 200 mg
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12)
Description
SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected (ie, HCV RNA <25 IU/mL) at follow-up Week 12. DCV=daclatasvir, SOF=sofosbuvir.
Time Frame
Follow-up Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)
Description
SVR24 was defined as participant's hepatitis C virus RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 24. DCV=daclatasvir, SOF=sofosbuvir.
Time Frame
Follow-up Week 24
Title
Percentage of Participants With Viral Breakthrough During the Treatment Period
Description
Viral breakthrough is defined as any confirmed increase in viral load ≥1 log from nadir or any confirmed hepatitis C virus RNA levels ≥25 IU/mL on or after Week 8.
Time Frame
First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group)
Title
Percentage of Participants Who Experienced Viral Relapse During Follow-up Period
Description
Viral relapse during follow-up is defined as any confirmed quantifiable hepatitis C virus (HCV) RNA ≥25 IU/mL with HCV RNA levels less than the lower limit of quantitation, target detected or target not detected, ie, HCV RNA <25 IU/mL at the end of treatment.
Time Frame
Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks)
Title
Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24
Description
Change from baseline in log10 HCV RNA at scheduled sampling time.
Time Frame
Baseline, Follow-up week 24
Title
Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue Therapy
Description
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe.
Time Frame
First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group)
Title
Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up Period
Description
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe
Time Frame
AEs: From Day 1 of follow-up period (Week 13 or 25) up to study discharge (up to 72 weeks). SAEs: From Day 1 of follow-up period (Week 13 or 25) up to 30 days after study discharge (up to 74 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women, ages 18 to 70 years. Participants infected with hepatitis C virus (HCV) genotype 1, 2, or 3, with no previous exposure to an interferon formulation (ie, interferon-alpha, pegylated interferon-alpha) ribavirin, or other HCV-specific direct-acting antiviral (including daclatasvir and PSI-7977). Patients should have chronic hepatitis C genotype 1a, 1b, 2, or 3 as documented by: positive test results for anti-HCV antibody; HCV RNA; or a HCV genotype at least 6 months prior to screening, and HCV RNA and anti-HCV antibody at the time of screening. Exclusion Criteria: Evidence of a medical condition associate with chronic liver disease other than HCV. History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis. History of hemophilia. History of torsade de pointes. Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment. History of gastrointestinal disease or surgical procedure (except cholecystectomy). History of clinically significant cardiac disease. Blood transfusion within 4 weeks prior to study drug administration. Poor venous access. Any other medical, psychiatric, and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation in this study.
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
Southern California Liver Centers
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
Research And Education, Inc.
City
San Diego
State/Province
California
ZIP/Postal Code
92105
Country
United States
Facility Name
University Of Colorado Denver & Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University Of Florida Hepatology
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Miami Research Associates
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Mercy Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
Johns Hopkins University
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Facility Name
University Of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Bronx Va Medical Center 3c Sub-J
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Options Health Research, Llc
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Healthcare Research Consultants
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74135
Country
United States
Facility Name
University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Alamo Medical Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Metropolitan Research
City
Annandale
State/Province
Virginia
ZIP/Postal Code
22003
Country
United States
Facility Name
Dean Clinic
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53715
Country
United States
Facility Name
Local Institution
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
24428467
Citation
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218. Erratum In: N Engl J Med. 2014 Apr 10;370(15):1469.
Results Reference
derived
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

Study to Determine the Safety and Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) in Patients Who Have Previously Not Received the Standard of Care

We'll reach out to this number within 24 hrs