A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT02496078

Collaborator

(none)

207

Enrollment

Locations

Arms

18.1

Duration (Months)

7.1

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether a regimen consisting of daclatasvir and asunaprevir is effective in treatment-naive patients with chronic hepatitis genotype 1b infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Daclatasvir Drug: Asunaprevir	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

207 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active dual arm Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 24 week and follow up to week 48	Drug: Daclatasvir Daclatasvir tablet 60mg Drug: Asunaprevir Asunaprevir soft capsule 100 mg
Placebo Comparator: Placebo arm Daclatasvir placebo in tablet form QD and Asunaprevir placebo in soft capsule form BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 36 week and follow up to week 60	Drug: Daclatasvir Daclatasvir tablet 60mg Drug: Asunaprevir Asunaprevir soft capsule 100 mg

Arm

Intervention/Treatment

Active Comparator: Active dual arm

Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 24 week and follow up to week 48

Drug: Daclatasvir

Daclatasvir tablet 60mg

Drug: Asunaprevir

Asunaprevir soft capsule 100 mg

Placebo Comparator: Placebo arm

Daclatasvir placebo in tablet form QD and Asunaprevir placebo in soft capsule form BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 36 week and follow up to week 60

Drug: Daclatasvir

Daclatasvir tablet 60mg

Drug: Asunaprevir

Asunaprevir soft capsule 100 mg

Outcome Measures

Primary Outcome Measures

Proportion of treated subjects randomized to Active Dual therapy with Sustained Virologic Response (SVR12) [Post-treatment Week 12]
HCV RNA < Lower limit of quantitation (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12

Secondary Outcome Measures

Proportion of subjects with anemia on active Dual therapy [Post-treatment Week 12]
Proportion of subjects with neutropenia on active Dual therapy [Post-treatment Week 12]
Proportion of subjects with thrombocytopenia on active Dual therapy [Post-treatment Week 12]
On treatment safety, as measured by frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) [Post-treatment week 12]
Differences in rates of selected Grade 3-4 laboratory abnormalities for hematology between treatments (DCV + Asunaprevir (ASV) vs PBO) [first 12 weeks on treatment]
Differences in rates of selected Grade 3-4 laboratory abnormalities for liver function between treatments (DCV + Asunaprevir (ASV) vs PBO) [first 12 weeks on treatment]
Proportion of subjects with SVR12 by the rs12979860 single nucleotide polymorphism (SNP) in the interleukin (IL) -28B gene for each cohort [Post-treatment visit week 12]
Proportion of subjects with hepatitis C virus (HCV) RNA < LLOQ-TD/TND in each arm at various intervals after the initiation of active Dual therapy [post-treatment visit Week 24]
Proportion of subjects who achieve HCV RNA < LLOQ-TND at each arm at various intervals after the initiation of active Dual therapy [post-treatment visit Week 24]
Proportion of treated subjects with SVR12 for subjects randomized to placebo [Post-treatment visit week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

Patients chronically infected with HCV Genotype 1b
No previous exposure to any interferon formulation, Ribavirin (RBV), and HCV direct acting antiviral agent
HCV RNA viral load ≥ 10,000 IU/mL at screening
Seronegative for HIV and HBsAg
BMI of 18-35 kg/m2, inclusive
Patients with compensated cirrhosis are permitted

Exclusion Criteria:

Infection with HCV other than genotype (GT) -1b
Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
Evidence of a medical condition contributing to chronic liver disease other than HCV
Diagnosed or suspected hepatocellular carcinoma or other malignancies
Uncontrolled diabetes or hypertension
History of moderate to severe depression. Well-controlled mild depression is allowed
Confirmed alanine aminotransferase (ALT) ≥ 5x Upper Limit of Normal (ULN)
Confirmed platelet count < 50,000 cells/mm3
Confirmed hemoglobin < 8.5 g/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Beijing	Beijing	China	100015
2	Local Institution	Beijing	Beijing	China	100034
3	Local Institution	Beijing	Beijing	China	100050
4	Local Institution	Beijing	Beijing	China	100054
5	Local Institution	Guangzhou	Guangdong	China	510060
6	Local Institution	Guangzhou	Guangdong	China	510515
7	Local Institution	Shi Jia Zhuang	Hebei	China	050051
8	Local Institution	Changsha	Hunan	China	410008
9	Local Institution	Nanjing	Jiangsu	China	210002
10	Local Institution	Nanjing	Jiangsu	China	210003
11	Local Institution	Nanjing	Jiangsu	China	210029
12	Local Institution	Zhenjiang	Jiangsu	China	212000
13	Local Institution	Changchun	Jilin	China	130021
14	Local Institution	Shenyang	Liaoning	China	110002
15	Local Institution	Shenyang	Liaoning	China	110006
16	Local Institution	Qingdao	Shandong	China	266011
17	Local Institution	Shanghai	Shanghai	China	200025
18	Local Institution	Shanghai	Shanghai	China	200062
19	Local Institution	Shanghai	Shanghai	China	200083
20	Local Institution	Xi'an	Shanxi	China	710038
21	Local Institution	Xi'an	Shanxi	China	710061
22	Local Institution	Chengdu	Sichuan	China	610041
23	Local Institution	Beijing		China	100039
24	Local Institution	Busan		Korea, Republic of	47392
25	Local Institution	Seoul		Korea, Republic of	07061
26	Local Institution	Seoul		Korea, Republic of	08308
27	Local Institution	Moscow		Russian Federation	127015
28	Local Institution	St. Petersburg		Russian Federation	191167
29	Local Institution	St.petersburg		Russian Federation	190103