Clinical Protocol AI447-029 A Phase 3, Open-Label Study with Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin with Chronic Hepatitis C Genotypes 1 or 4 Infectio

Phase 3

Completed

Conditions: Chronic Hepatitis C
liver diseases
10047438

Registration Number: NL-OMON37569

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

* Males and females, * 18 years of age;
* HCV Genotype 1 or 4 who previously failed treatment with P/R, classified as previous null and partial responders based on previous therapy;
* HCV RNA > 10,000 IU/mL;
* Seronegative for HIV and HBsAg;
* Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at
approximately 25% of treated population). If a subject does not have cirrhosis, a liver biopsy within
three years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is
present, any prior liver biopsy is sufficient. For countries where liver biopsy is not required prior to
treatment and where non-invasive imaging tests (Fibroscan® ultrasound) are approved for staging of liver disease, non-invasive imaging test results may be used to assess the extent of liver disease.

Exclusion Criteria

* Prior treatment of HCV with HCV direct acting agent (DAA);
* Evidence of a medical condition contributing to chronic liver disease other than HCV;
* Evidence of decompensated liver disease including, but not limited to, a history or presence of
ascites, bleeding varices, or hepatic encephalopathy;
* Diagnosed or suspected hepatocellular carcinoma or other malignancies;
* Uncontrolled diabetes or hypertension;
* Total bilirubin * 34 *mol/L (or * 2 mg/dL) unless subject has a documented history of Gilbert*s
disease;
* Confirmed ALT * 5x ULN;
* Confirmed Albumin * 3.5 g/dL (35 g/L)
* Confirmed ANC < 0.5 x 109 cells/L
* AFP > 100 ng/mL OR * 50 and * 100 mg/mL requires a liver ultrasound and subjects with
findings suspicious of HCC are excluded;
* Neutrophil count < 1500 cells/*L (<1,200 cells/*L for Black/African-Americans);
* Platelet count < 90,000 cells/*L;
* Hemoglobin < 12 g/dL for females or <13 g/dL for males;
* Any criteria that would exclude the subject from receiving P/R;
* Hematologic, biochemical and serologic criteria (growth factors may not be used to achieve trial
entry requirements)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint<br /><br>* Antiviral activity, as determined by the proportion of subjects with SVR-12,<br /><br>defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected<br /><br>with HCV genotype 1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Endpoints<br /><br>* On-treatment safety, as measured by frequency of SAEs and discontinuations<br /><br>due to AEs through the end of treatment (maximum of 24 weeks) plus 7 days;<br /><br>* Proportion of subjects with SVR-12 (HCV RNA < LOQ at post-treatment Week 12)<br /><br>by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene;<br /><br>* Proportion of subjects with HCV RNA undetectable at each of the following<br /><br>timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up<br /><br>to 24 weeks), post-treatment Week 12 or post-treatment Week 24;<br /><br>* Proportion of subjects with HCV RNA < LOQ at each of the following<br /><br>timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; End<br /><br>of Treatment (EOT) (up to 24 weeks), post-treatment Week 24 (SVR-24).<br /><br>* Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12)<br /><br>for HCV genotype 4 subjects</p><br>