A Phase 2, Randomized, Open-Label trial of GS-9256 plus GS-9190 alone and in combination with Ribavirin for 28 days in Treatment Naive Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.
- Conditions
- Chronic Hepatitis C Virus InfectionMedDRA version: 12.0Level: LLTClassification code 10008912Term: Chronic hepatitis C
- Registration Number
- EUCTR2009-013690-18-DE
- Lead Sponsor
- Gilead Sciences Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 45
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1.Male or female, aged from 18 to 70 years old, inclusive.
2.Willing and able to provide written informed consent.
3.Body mass index (BMI) from 18 to 36 kg/m^2, inclusive.
Note: BMI may be calculated according to either of the following formulae:
BMI = weight in pounds x 703/(height in inches)^2 or weight in kilograms/(height in meters)^2
4. HCV infection limited to genotype 1.
5. Subjects must have baseline plasma HCV RNA = 3 log10 IU/mL at screening, but < 7.2 log10 IU/mL.
6.Liver biopsy results (or combined results of FibroTest or FibroScan, if considered acceptable by regulators and ethics committess on a country-by-country basis) within the past 2 years prior to screening indicating the absence of cirrhosis. If a liver biopsy or combined FibroTest and FibroScan performed more than 1 year prior to Screening indicates Stage 3 fibrosis, the medical monitor must be consulted prior to enrollment (i.e., consensus must be reached that progression to cirrhosis with hepatic impairment is unlikely to have occurred in the time interval from procedure to enrollment). Alternative methods to evaluate cirrhosis may be used provided they are approved in advance by the Medicla Monitor.
7.Chronic HCV infection will be documented by (1) a positive anti-HCV antibody test or evidence of HCV RNA (i.e., viral load or genotype) (2) a liver biopsy (or FibroTest or FibroScan results where appropriate) consistent with chronic HCV infection, or (3) elevated ALT values (i.e. above the normal range) at any point in within one year prior to screening.
On a case-by-case the sponsor will consider permitting enrollment of patients with clear cut clinical histories of chronic infection in circumstances where laboratory documentation cannot be retrieved.
8.Eligible subjects must also be HCV treatment-naïve, defined as no prior exposure to IFNa, RIBA, or experimental HCV therapy, with imminent plans to start standard of care therapy with PEG/RIBA.
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, AST, and GGT = 5 x the upper limit of normal (reference) range (ULN); white blood cell count = 2,500 cells/µL; absolute neutrophil count (ANC) = 1,500 cells/mm3 (unless considered a physiologic variant discussed with and approved by the Gilead medical monitor); potassium and magnesium within normal limits; TSH within normal limits (unless currently being treated for hypothyroidism or the TSH abnormality is not considered to be clinically significant after consultation with the Gilead Medical Monitor); hemoglobin (Hb) = 13 g/dL for males and Hb = 12 g/dL for females.
11.Creatinine clearance (CLcr) = 50 mL/min, as calculated by the Cockcroft-Gault equation using lean body weight:
CLer (mL)/min)= (140-Age) x LBW/72 x Scr (x0.85 for female subjects)
where:
Age is calculated in years and Scr is the subject’s measured serum creatinine (in mg/dL).
LBW is the subject’s lean body weight in kilograms, calculated as:
Male: LBW = 50 + 2.3*[(height in cm – 152.4) / 2.54] OR 50 + 2.3*(height in inches – 60)
Female: LBW = 45.5 + 2.3*[(height in cm – 152.4) / 2.54] OR 45.5 + 2.3*(height in inches – 60)
If a subject’s height is less than or equal to 152.4 cm (60 inches), then his LBW is 50 kg and her LBW is 45.5 kg.
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1.Female of child-bearing potential (defined as a non-menopausal female or a female who is menopausal < 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure), pregnant woman, or nursing woman.
[Note: Female subjects who are post-menopausal for < 2 years are required to have a confirmed folloicle-stimulating hormone (FSH) level of = 40 mIU/mL at the screening evaluation).]
2.Male with a female partner who is pregnant or is planning to become pregnant within 7 months of anticipated last dose of RIBA.
3.Males who are unwilling to use two forms of effective birth control throughout the duration of study treatment and for 7 months after the last dose of RIBA. 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 or fasting glucose = 150 mg/dL) .
6.History of hemoglobinopathy (e.g. thalassemia), retinal disese, sarcoidosis
7.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
8.Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
9.Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) or multiple HCV genotypes
10.Chronic use of systemic immunosuppressive agents
11.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.
12.Severe chronic obstructive pulmonary disease
13.History of significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction < 40% ) or a family history of Long QT Syndrome. The following ECG abnormalities at screening are exclusionary: QTcF (QT corrected using Fridericia’s formula) of > 450 msec; QRS > 120 msec (left or right hemiblock is not exclusionary); bradycardia (< 45 beats per minute); second or third degree heart block. A history of clinically significant coronary artery disease without prior myocardial infarction will require consultation with a cardiologist and the medical monitor prior to enrollment
Fridericia’s formula:QTcF=QT/RR0^.333
14.Known cirrhosis, Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis)
15.History of solid organ transplantation
16.Suspicion of hepatocelluar 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
17.Total bilirubin > ULN or known diagnosis of Gilbert’s syndrome
18.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
19.Subjects with or a history of clinically
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