A Phase 2a/2b study of BMS-650032 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive Subjects with Genotypes 1 and 4 Chronic Hepatitis C Infection.
- Conditions
- Chronic Hepatitis C Virus Infection (Genotypes 1 and 4) in Treatment-Naive SubjectsMedDRA version: 9.1Level: LLTClassification code 10008912Term: Chronic hepatitis C
- Registration Number
- EUCTR2009-013652-69-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 435
1) Signed Written Informed Consent
a) Freely given informed consent must be obtained from subjects prior to clinical
trial participation, including informed consent for any screening procedures
conducted to establish subject eligibility for the study.
2) Target Population
a) Subjects chronically infected with HCV genotype 1 as documented by: positive
for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6
months prior to screening, and positive for HCV RNA and anti-HCV anti-body at
the time of screening (Stages 1 and 2);
b) Subjects chronically infected with HCV genotype 4 as documented by: positive
for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6
months prior to screening, and positive for HCV RNA and anti-HCV anti-body at
the time of screening (Stage 2 only);
c) HCV RNA viral load of = 100,000 IU/mL at screening;
d) Results of a biopsy obtained = 24 months prior to randomization showing no
evidence of cirrhosis (Stage 1 only);
e) Body Mass Index (BMI) of 18 to 35 kg/m², inclusive. BMI = weight (kg)/[height
(m)]² at screening
3) Age and Sex
a) Men and women, ages 18 to 70;
b) Women of childbearing potential (WOCBP), unless non-heterosexual active or
who have vasectomized male partners, and sexually active men (unless
vasectomized) with female partners who are WOCBP must use two separate
forms of contraception, one of which must be an effective barrier method (eg,
condom with spermicide), from screening throughout the duration of the study
and for 24 weeks after the last dose of ribavirin. In addition, WOCBP must agree
to the pregnancy testing schedule specified in this protocol. Oral contraceptive
pills (OCPs) may be used in this study, but cannot be considered one of the two
effective forms of contraception required because drug interaction studies
verifying the effectiveness of OCPs when used with BMS-650032 have not been
completed. Men (unless vasectomized) with female partners who are WOCBP
must agree to inform their female partners of the protocol-specified contraception
requirements and pregnancy testing recommendations during treatment and
post-treatment (monthly pregnancy testing on-treatment and following
discontinuation of RBV for 6 months post-treatment or the duration specified in
the label used for RBV in that country), and agree to adhere to these
recommendations for both the on-treatment and post-treatment follow-up period.
WOCBP are defined as a non-menopausal female or a female with menopause
= 2 years and who has not had a hysterectomy, bilateral tubal ligation, bilateral
oophorectomy or medically documented ovarian failure. Female subjects who are
postmenopausal for less than two years are required to have FSH > 40 mIU/mL. If
the FSH is = 40 mIU/mL, the subject must agree to use two forms of
contraception to participate in the study.
Women are considered surgically sterile only if they have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy.
Post menopause is defined as:
• Amenorrhea = 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement
therapy (HRT), a documented serum follicle stimulating hormone (FSH) level
> 40 mIU/mL.
Non-menopausal women who are using oral contraceptives, other hormonal
contraceptives (vaginal products, skin patches, or implanted or injectable
products), or mechanical products such as an intrauterine device or barrier
methods (diaphragm, condoms, spermici
1)Sex and Reproductive Status
a)WOCBP unwilling or unable to use an acceptable method to avoid
pregnancy (two effective forms of contraception) for the entire study period (on
treatment) and for up to 24 weeks after the last dose of investigational product
b)Women who are pregnant of breastfeeding
c)Women with positive pregnancy test on enrollment or prior to investigational
product administration
d)Sexually active fertile men not using effective birth control if their partners are
WOCBP
e)Sexually active fertile men whose partners are pregnant at screening
(contraindicated with RBV use)
2)Medical History and Concurrent Diseases
a)Evidence of medical condition associated with chronic liver disease other than HCV
b)Evidence of decompensated cirrhosis based on radiologic criteria or biopsy results
and clinical criteria (in Stage 2) (Note: Subjects with compensated cirrhosis may
be enrolled in Stage 2)
c)Evidence of HCC documented by ultrasound (U/S), computed tomography (CT)
scan, or magnetic resonance imaging (MRI) within 12 months of randomization
d)Co-infection with HBV, HIV-1 or HIV-2 at screening
e)History of variceal bleeding, hepatic encephalopathy, or ascites requiring
management with diuretics or paracentesis
f)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
g)Any gastrointestinal disease or surgical procedure that may impact the absorption
of study drug;
h)Any other medical, psychiatric and/or social reason including active substance or
alcohol abuse, as defined by DMS IV, Diagnostic Criteria for Drug and Alcohol
Abuse (see Protocol Appendix 3), which in the opinion of the investigator, would make the
candidate inappropriate for participation in this study
i)Inability to tolerate oral medication
j)Poor venous access
k)Liver transplant recipients
3)Physical & Laboratory Test Findings
a)ALT =5 x ULN
b)Total bilirubin =2 mg/dL (or = 34 µmol/L)
c)INR= 1.7
d)Albumin =3.5 g/dL (35 g/L)
e)Creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) =50 mL/min
f)Any ECG finding which, in the opinion of the investigator, would make the
candidate inappropriate for participation in this study (ie, corrected QT value >
450 msec, second/third degree bundle branch block)
g)Positive HBs Antigen
4)Medical History or Laboratory Findings that Exclude Subject from pegIFNa or
RBV Therapy
The following exclusion criteria are based on guidelines or recommendations from the
pegIFNa and RBV package inserts.
a)Severe psychiatric disease, especially untreated or unstable depression, that would
prohibit use of pegIFNa as judged by the investigator
b)History of hemoglobinopathies (ie, thalassemia major or sickle cell anemia),
diagnoses associated with an increased baseline risk for anemia (eg,
spherocytosis), hemolytic anemia, or diseases in which anemia would be
medically problematic
c)History of thyroid dysfunction not adequately controlled or screening thyroid
function tests that indicate abnormal thyroid function
d)History of chronic pulmonary disease associated with functional limitation
e)History of cardiomyopathy, coronary artery disease (including angina),
interventive procedure for coronary artery disease (including angioplasty, stent
procedure, or cardiac bypass surgery), ventricular arrhythmia, or other clinically
significant cardiac disease
f)Pre-existing ophthalmologic disorders considered clinically signif
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method