Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha-2b and Ribavirin) in Japanese Patients

Hepatitis C Infection Clinical Trial

Official title:

A Phase 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2b (PegIntron®) and Ribavirin (Rebetol®) in Japanese Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01016912
• Other study ID #: AI444-021
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2009
• Last updated: September 23, 2015
• Start date: December 2009
• Est. completion date: September 2010

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to identify at least 1 dose of daclatasvir that is safe, well tolerated, and efficacious when combined with peginterferon-alfa and ribavirin for the treatment of hepatitis C virus genotype 1 in chronically infected patients who are treatment-naïve and nonresponsive to the standard of care

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Key Inclusion Criteria:

• Patients chronically infected with hepatitis C virus (HCV) genotype 1

• HCV RNA viral load =10*5* IU/mL at screening

• Naïve or nonresponsive to the current standard of care

Key Exclusion Criteria:

• Cirrhosis

• Hepatocellular carcinoma

• Coinfection with hepatitis B virus, HIV-1 or HIV-2

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
• Hepatitis C Infection

Intervention

Drug:
• BMS-790052
Tablets, Oral, 10 mg, daily, 24-48 weeks
• BMS-790052
Tablets, Oral, 60 mg, daily, 24-48 weeks
• Placebo
Tablets, Oral, 0 mg, daily, 48 weeks
• Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
• Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks

Locations

Country	Name	City	State
Japan	Local Institution	Hiroshima City	Hiroshima
Japan	Local Institution	Iruma-Gun	Saitama
Japan	Local Institution	Kawasaki-Shi	Kanagawa
Japan	Local Institution	Minato-Ku	Tokyo
Japan	Local Institution	Sapporo-Shi	Hokkaido
Japan	Local Institution	Suita-Shi	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Death as Outcome	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug.	From baseline to 30 days after last dose of study drug	Yes
Other	Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results	Clinically significant marked abnormalities in laboratory test results graded by the Division of AIDS grading table, 2004. Hemoglobin: Grade 3= <7.0 to 8.9 g/dL, Grade 4= <7.0 g/dL. Lymphocytes: Grade 3= 350-499 cells/mm^3, Grade 4= <350 cells/mm^3. Neutrophils: Grade 3= 500-999 cells/mm^3, Grade 4= <500 cells/mm^3. White blood cells (WBC): Grade 3= 1000-1499 cells/mm^3, Grade 4= <1000 cells/mm^3. Alanine aminotransferase (ALT): Grade 3= 5.1-10*upper limit of normal (ULN), Grade 4= >10.0*ULN. Aspartate aminotransferase (AST): Grade 3= 5.1-10*ULN, Grade 4= >10.0*ULN. Total bilirubin: Grade 3= 2.6-5*ULN, Grade 4= >5.0*ULN.	From baseline to 30 days after last dose of study drug	Yes
Primary	Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at both Weeks 4 and 12. HCV RNA levels were measured by Tobas TaqMan HCV Auto from the central laboratory.	At Weeks 4 and 12 on treatment	Yes
Secondary	Percentage of Participants With Rapid Virologic Response (RVR)	RVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 4. HCV RNA levels were measured by CobasTaqMan HCV Auto from the central laboratory .	At Week 4 on treatment	No
Secondary	Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 12 on treatment. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory	At Week 12 on treatment	No
Secondary	Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24	SVR at follow-up Week 4 (SVR4), follow-up Week 12 (SVR12), and follow-up Week 24 (SVR24) is defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at each of these timepoints. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory .	Follow-up Weeks 4, 12, and 24	No
Secondary	Percentage of Participants With Virologic Failure	Virologic failure is defined by the following 6 categories: 1.Virologic breakthrough, defined as confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed HCV RNA =limit of quantitation (LOQ) after confirmed undetectable HCV RNA while on treatment. 2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment. 3. Failure to achieve early virologic response, defined as <2 log10 decrease in HCV RNA from baseline at Week 12 of treatment. 4. Detectable HCV RNA at Week 12, and HCV RNA =LOQ at Week 24 of treatment. 5. Detectable HCV RNA at end of treatment (including early discontinuation). 6 Relapse, defined as detectable HCV RNA during follow-up after undetectable HCV RNA levels at end of treatment.	From on-treatment Week 1 to Follow-up Week 24	No

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