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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359644
• Other study ID #: AI444-040
• Status: Completed
• Phase: Phase 2
• First received: May 23, 2011
• Last updated: September 23, 2015
• Start date: June 2011
• Est. completion date: October 2013

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: October 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• PSI-7977
Tablets, oral, 400 mg, once daily
• Daclatasvir
Tablets, oral, 60 mg, once daily
• Ribavirin
Tablets, oral, 200 mg

Locations

Country	Name	City	State
Puerto Rico	Local Institution	San Juan
United States	University Of Michigan Health System	Ann Arbor	Michigan
United States	Metropolitan Research	Annandale	Virginia
United States	University Of Colorado Denver & Hospital	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Bronx Va Medical Center 3c Sub-J	Bronx	New York
United States	Southern California Liver Centers	Coronado	California
United States	University Of Florida Hepatology	Gainesville	Florida
United States	Johns Hopkins University	Lutherville	Maryland
United States	Dean Clinic	Madison	Wisconsin
United States	Weill Cornell Medical College	New York	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Alamo Medical Research	San Antonio	Texas
United States	Research And Education, Inc.	San Diego	California
United States	Miami Research Associates	South Miami	Florida
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Options Health Research, Llc	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Pharmasset

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Follow-up Week 12	No
Secondary	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.	Follow-up Week 24	No
Secondary	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.	First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group)	No
Secondary	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.	Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks)	No
Secondary	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.	Baseline, Follow-up week 24	No
Secondary	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.	First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group)	Yes
Secondary	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	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)	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form