Treatment of chronic HCV genotype 1 infection. MedDRA version: 9.1 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV)
Conditions
Interventions
Product Name: FILIBUVIR
Product Code: PF-00868554
Pharmaceutical Form: Tablet
INN or Proposed INN: Filibuvir
CAS Number: 877130-28-4
Current Sponsor code: PF-00868554
Concentration unit: mg milligram(
Sponsors
Pfizer Inc, 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Male or female subjects at least 18 years of age. 2.A negative pregnancy test at Screening and immediately prior to start of study medication for Women of Child Bearing Potential (WOCBP). NOTE: WOCBP includes any female who has experienced menarche and who has not undergone hysterectomy, bilateral oophorectomy or tubal ligation or is not post-menopausal (aged >45, amennorheic for >2 years, and serum FSH levels >30 IU/L). Even women who are using mechanical products (intrauterine devices; barrier methods) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (eg, vasectomy), should be considered to be of child bearing potential. 3. Willingness to utilize effective barrier contraception for WOCBP, males and their partners, throughout the duration of the study and for at least 6 months following the last dose of study medication. In addition, WOCBP must use another acceptable method of contraception from screening to at least 6 months after the trial. Acceptable contraception includes highly effective intrauterine devices or vasectomised partner. NOTE: oral, transdermal, implantable, or injectable hormone therapy is NOT allowed. 4. HCV seropositive. 5. HCV RNA =10,000 IU/mL at screening. 6. HCV Genotype 1. Subjects infected with a non-genotype 1 strain or mixed genotypes are not eligible. 7. Treatment naïve (no prior treatment with IFN-alpha+/- RBV regimens or investigational anti-HCV agents). 8. Liver biopsy within two years (24 months) of Screening with non-cirrhotic fibrosis classification (Ishak score =4 or equivalent). A copy of the pathology report must be available at the study site prior to randomization. For those subjects with liver biopsy outside of the time window or for those subjects with no history of liver biopsy, a biopsy must be performed prior to randomization. 9. Ultrasound within 6 months of Screening for 1) those subjects with bridging fibrosis or 2) those subjects with AFP >50 and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the trial: 1. Co-infection with either HIV or HBV. 2. Infection with a non-genotype 1 strain of HCV or mixed genotypes. 3. Evidence of severe or decompensated liver disease, as evidenced by any of the following at Screening: a. Child-Pugh score >6; b. Total serum bilirubin >2.5X ULN and direct bilirubin >1.5X ULN; c. Serum albumin 1.5X ULN or INR >2.0X ULN; e. AST or ALT >10X ULN; f. History of ascites, bleeding varices, hepatic encephalopathy or hepatocellular carcinoma. 4. Subjects with liver disease unrelated to HCV infection including but not limited to: a. Hemochromatosis; b. Genetic liver disease: 1. Alpha-1 antitrypsin deficiency; 2. Wilson’s disease. c. Auto-immune disease; 1. Auto-immune hepatitis; 2. Auto-immune cholestatic disease. d. Drug induced liver disease (history of ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months; e. Cholestatic liver disease; bile duct obstruction; f. Alpha-fetoprotein (AFP) levels greater than 100 ng/ml; g. Malignant neoplastic disease; 5. Pre-existing medical condition that makes the subject unsuitable for treatment with pegIFN alpha/RBV therapy per product labeling including, but not limited to: a. Ocular abnormalities such as retinopathy, cotton wool spots, optic nerve disorders, retinal hemorrhage; etc. b. Major psychiatric disorders (severe depression, schizophrenia, psychosis, or a history of a suicide attempt). 6. Laboratory abnormality at Screening that makes the subject unsuitable for treatment with pegIFN alpha/RBV therapy per product labeling including, but not limited to: a. HbA1c >8.5%; b. Estimated creatinine clearance of 1.2 x ULN or 1:640; e. Hematologic abnormalities: hemoglobin <12 g/dL (women) or <13 g/dL (men), platelet count <120,000 cells/mm3, and/or neutrophil count <1,500 cells/mm3; 7. Abnormal ECG suggestive of clinically significant cardiac disease or history of significant cardiac disease; 8. History of organ transplant; 9. Contraindicated medications being taken by the subject at the time of randomization that must be continued during the study period, including potent CYP3A4 inhibitors, sensitive CYP3A4 substrates, CYP3A4 substrates with narrow therapeutic range and CYP3A4 inducers. 10. Active alcohol or substance abuse sufficient, in the Investigator’s judgment, to prevent adherence to study medication and/or follow-up; 11. Pregnant or nursing females; 12. Males whose female partner is pregnant; 13. Unwilling or unable to comply with the Lifestyle guidelines (eg, no active drug or alcohol abuse); 14. Participation in other studies within 30 days before the current study begins and/or during study participation; 15.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. NOTE: Subjects with laboratory values outside of the criteria specified above may be retested. If upon retest a laboratory value is within 10% of th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine if the addition of filibuvir to a standard of care (SOC) regimen of pegylated interferon alpha 2a (Pegasys) and ribavirin (Copegus) significantly increases the proportion of subjects who achieve a sustained viral response (SVR) - undetectable HCV RNA at week 72 compared to pegIFN/RBV alone. ;Primary end point(s): ? Proportion of subjects with undetectable HCV RNA at Week 72 (SVR).;Secondary Objective: Secondary objectives include determination of the following : •Proportion of subjects in Path 2 only with undetectable HCV RNA at Weeks 4 (rapid viral response (RVR)), 12 (early viral response (EVR)), 24 and 48. •Proportion of subjects with undetectable HCV RNA 12 weeks following the completion of therapy (SVR12). •Proportion of subjects in Path 1 only with undetectable HCV RNA 24 weeks following the completion of therapy (SVR24). •Proportion of subjects with breakthrough or relapsed viremia in each treatment arm. •Assess the safety, tolerability and pharmacokinetics of filibuvir administered in combination with pegIFN and RBV. | — |
Countries
Belgium, France, Germany, Hungary, Spain
Outcome results
None listed