Clinical trial NCT01995266: Phase III China GT 1b Interferon (IFN) Intolerant Prev Exclude Dual
Official title: A Phase 3, Open-Label Study With Daclatasvir And Asunaprevir (DUAL) for Subjects With Genotype 1b Chronic Hepatitis C (HCV) Infection Who Are Intolerant or Ineligible to Interferon Alfa Therapies With or Without Ribavirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-11-26
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with chronic hepatitis genotype 1b, who are intolerant or ineligible to Interferon alfa therapy with or without Ribavirin, will be treated for 24 weeks with Daclatasvir (DCV) Dual regimen (= Daclatasvir + Asunaprevir) and followed for an additional 24 weeks post-treatment in order to determine the safety and efficacy of the DCV DUAL regimen


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

Inclusion Criteria:

* Males and females, ≥ 18 years of age
* Subjects chronically infected with HCV Genotype (GT)-1b only as documented by positive HCV RNA and anti-HCV antibody at screening and either:

  1. Positive anti-HCV antibody, HCV RNA or positive HCV genotype test at least 6 months prior to screening

     or
  2. Liver biopsy consistent with chronic HCV infection (evidence of fibrosis and/or inflammation)
* Subjects who are intolerant to previous therapy with Interferon Alfa (IFNα) either with or without Ribavirin (RBV) (I±R)(independent of previous response to therapy) or ineligible for I±R and who meet one of the criteria below:

  1. Anemia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in hemoglobin to \< 8.5 g/dL during therapy (documented); the I±R ineligibles are subjects who have a screening hemoglobin \< 10.0 g/dL and ≥ 8.5 g/dL

     OR
  2. Neutropenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in absolute neutrophil count (ANC) to \< 0.5 x 10(9) during therapy (documented); the I±R ineligibles are subjects who have a screening ANC \< 1.5 x 10(9) cells/L and ≥ 0.5 x 10(9) cells/L

     OR
  3. Thrombocytopenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in platelet counts \< 25,000 cells/mm3 during therapy (documented); the I±R ineligibles are subjects who have a screening platelet count of \< 90 x 10(9) cells/L and ≥ 50 x 10(9) cells/L
* HCV RNA ≥ 10,000 IU/mL
* Seronegative for Human Immunodeficiency Virus (HIV) and hepatitis B surface antigen (HBsAg)
* Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI = weight (kg)/ \[height(m)\]2 at screening
* Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 40%). 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 noninvasive 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 with HCV direct acting antiviral (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
* History of moderate to severe depression. Well-controlled mild depression is allowed
* Total bilirubin ≥ 34 µmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
* Confirmed alanine aminotransferase (ALT) ≥ 5 x upper limit of normal (ULN)
* Confirmed albumin \< 3.5 g/dL (35 g/L)
* Alpha-fetoprotein (AFP) \> 100 ng/mL OR ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of hepatocellular carcinoma (HCC) are excluded
* Confirmed hemoglobin \< 8.5 g/dL
* Confirmed ANC \< 0.5 x 10(9) cells/L
* Confirmed platelet count \< 50,000 cells/mm3

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 24 (SVR24)
timeFrame: 24 Weeks after treatment discontinuation (Follow-up Week 24)
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 12 (SVR12)
timeFrame: 12 Weeks after treatment discontinuation (Follow-up Week 12)
measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation
timeFrame: 7 days after treatment discontinuation
measure: Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24
timeFrame: 24 Weeks after treatment discontinuation (Follow-up Week 24)
measure: Percentage of Participants With HCV RNA< LLOQ Target Not Detected at the End of Treatment (Week 24)
timeFrame: Week 24 (End-of Treatment)
measure: Number of Participants With Rapid Virologic Response (RVR)
timeFrame: Treatment Week 4
measure: Percentage of Participants With Complete Early Virologic Response (cEVR)
timeFrame: Treatment Week 12
measure: Number of Participants With Extended Rapid Virologic Response (eRVR)
timeFrame: Treatment Week 4 and Week 12
measure: Number of Participants With HCV RNA < LLOQ Target Detected or Not Detected at the End of Treatment (Week 24)
timeFrame: Week 24 (End-of Treatment)
measure: Number of Participants With Virologic Response (VR) at Treatment Week 4 and 12
timeFrame: Treatment Week 4 and 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Guangdong
city: Chongqing
country: China
facility: Local Institution
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Wuhan
country: China
facility: Local Institution
state: Hubei
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
city: Xi'an
country: China
facility: Local Institution
state: Shan3xi
city: Xi'an
country: China
facility: Local Institution
state: Shan3xi
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Beijing
country: China
facility: Local Institution
state: Shanxi
city: Shanghai
country: China
facility: Local Institution
state: Shanxi
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Beijing
country: China
facility: Local Institution
city: Chongqing
country: China
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
state: Beijing
city: Busan
country: Korea, Republic of
facility: Local Institution
state: Guangdong
city: Seoul
country: Korea, Republic of
facility: Local Institution
state: Guangdong
city: Daegu
country: Korea, Republic of
facility: Local Institution
state: Hunan
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
state: Guangdong
city: Tainan
country: Taiwan
facility: Local Institution
state: Guangdong
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: