Study to evaluate the effects of a combination therapy of antiviral agents for the treatment of Hepatitis C Virus Infection.
- Conditions
- Chronic Hepatitis C Virus InfectionMedDRA version: 14.0Level: LLTClassification code 10008912Term: Chronic hepatitis CSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2010-023952-10-GB
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 245
1. Male or female, aged from 18 to 70 years old, inclusive. Where required by local law or regulation, the participation of female subjects may be limited to women of nonchildbearing potential or, if deemed appropriate, to males only in that country.
2. Willing and able to provide written informed consent.
3. Chronic HCV infection for at least 6 months prior to Baseline (Day 1) in subjects
currently positive for HCV RNA and anti-HCV antibody.
4. Subjects must have liver biopsy results (performed no more than 2 years prior to
screening) indicating the absence of cirrhosis.
5. HCV infection limited to genotype 1a or 1b.
6. Detectable plasma HCV RNA at Screening.
7. BMI between 18 and 36 kg/m2.
8. Eligible subjects must also be HCV treatment naïve, defined as no prior exposure to IFN-
a, RBV, or other approved or experimental HCV therapy, and must be eligible to start
standard of care therapy with PEG/RBV.
9. QTcF interval (QT corrected using Fridericia’s formula) must be = 450 msec as
determined from screening ECG.
10. Subjects must have the following laboratory parameters at screening: ALT and AST = 10 × the upper limit of normal (reference) range (ULN); hemoglobin (Hb) = 12 g/dL; white blood cell count = 2,500 cells/µL; absolute neutrophil count (ANC) = 1,500 cells/mm3; potassium and magnesium within normal limits; TSH not elevated
above upper limits of normal.
11. Creatinine clearance (CLcr) = 50 mL/min.
12. Able to comply with the dosing instructions for study drug administration and available to complete the study schedule of assessments.
13. Has not been treated with any investigational drug within 30 days of the screening visit in this study.
14. Of generally good health as determined by the Investigator, based upon physical
examination, laboratory parameters, ECG findings, vital signs, and medical history;
physical examination must be inclusive of retinal exam (e.g., opthalmoscopic or slit lamp evaluation).
15. Women of childbearing potential (i.e., a non-menopausal female or a female postmenopausal < 2 years, who have not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum ß-human chorionic gonadotropin (hCG) at screening and negative urine ß-hCG at Baseline (Day 1) prior to the first study drug administration (see also Inclusion criterion 1). Female subjects of childbearing potential and male subjects with a female partner of childbearing potential must agree that they and their partner will use effective contraception (two separate forms of contraception simultaneously, one of which must be a male condom with spermicide) from screening throughout the duration of study treatment and for at least 7 months after the last dose of RBV.
16. Lactating females must agree to discontinue nursing during the course of the study.
17. If male, agree to refrain from sperm donation for at least 7 months after the last dose of RBV.
18. Subject understands long-term commitment for study participation and is willing to adhere to study-specific requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 221
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
1. Pregnant women or women who may wish to become pregnant during the course of the study
2. Male with a female partner who is pregnant or is planning to become pregnant within 7 months of anticipated last dose of RBV. It is the responsibility of the male subject to ensure that his partner (or partners) is not pregnant prior to entry into the study and does not become pregnant during the treatment and for 7 months after the last dose of RBV.
3. Males and females of reproductive potential who are unwilling to use two forms of
effective birth control throughout the duration of study treatment and for at least 7
months after the last dose of RBV. One method should include a condom with spermicide for males.
4. Evidence of infection or co-infection with a non-genotype 1 HCV strain
5. Poorly controlled diabetes mellitus (hemoglobin A1c > 9 at Screening or fasting glucose= 150 mg/dL) unless treatment intervention has been reviewed with the Gilead Medical Monitor and improved glucose control is anticipated
6. History of hemoglobinopathy (e.g. thalassemia)
7. History of known retinal disease
8. History of sarcoidosis
9. History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen); subjects under evaluation for malignancy are not eligible.
10. Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
11. Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
12. Chronic use of systemic immunosuppressive agents
13. Presence of autoimmune disorders (e.g. systemic lupus erythematosus, rheumatoid arthritis, psoriasis of greater than mild severity). Subjects with treated hypothyroidism with normal TSH may be enrolled (the medical monitor must be consulted prior to enrollment).
14. Severe chronic obstructive pulmonary disease (e.g., FEV1 < 1.5 L, or a daily requirement for inhaled bronchodilators or corticosteroids)
15. History of significant cardiac disease
16. Known cirrhosis
17. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis)
18. History of solid organ transplantation
19. Suspicion of hepatocellular carcinoma; if a-fetoprotein > 50 ng/mL, enrollment is only allowed if results of appropriate diagnostic studies are inconsistent with a diagnosis of hepatocellular tumor
20. Direct (conjugated) bilirubin > ULN
21. Other signs of decompensated liver disease, as indicated by prothrombin time
> 1.5 × ULN, platelets < 90,000/mm3 or albumin < 3 g/dL at screening OR current or
prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage)
22. Subjects with or a history of clinically-significant illness or any other major medical
disorder that may interfere with subject treatment, assessment or compliance with the protocol.
23. Have a history of a primary gastrointestinal disorder that could interfere with the
absorption of the study drug or that could interfere with normal gastrointestinal anatomy or motility.
24. Subjects with, or a personal or family history of, acute porphyria.
25. Ongoing alcohol abuse in the judgment of the investigator
26. Have a history of clinically-relevant drug abuse
27. Positive urine scree
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