A Study to Evaluate the Safety and Efficacy of the Combined Single Dose of Dactavira Plus Or Dactavira in Egyptian Adults With Chronic Genotype 4 HCV Infection

Inclusion Criteria

• •1. Willing and able to provide written informed consent.
• •2. Male or female, age ≥ 18 years.
• •3. HCV RNA ≥ 104 IU/mL at screening.
• •4. Confirmed chronic HCV infection as documented by either:
• •a. A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit.
• •5. HCV genotype 4 at screening as determined by the Central Laboratory. Any non definitive results will exclude the subject from study participation.
• •a Presence of cirrhosis is defined as any one of the following:
• •* Liver biopsy within 2 years of Screening showing cirrhosis
• •* Fibroscan with a result of ≥ 12.5 kPa within 6 months of Baseline/Day1
• •6. Body mass index (BMI) ≥ 18 kg/m2.
• •7. Screening ECG without clinically significant abnormalities.
• •8. Subjects must have the following laboratory parameters at screening:
• •* ALT ≤ 10 x the upper limit of normal (ULN)
• •* AST ≤ 10 x ULN
• •* Hemoglobin ≥ 12 g/dL for male, ≥ 11 g/dL for female subjects
• •* Platelets \> 50,000 cells/mm3
• •* INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
• •* Albumin ≥ 3 g/dL
• •* Total Bilirubin ≤ 1.5 ULN
• •* Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
• •9. Subject has not been treated with any investigational drug or device within 30 days of the screening visit.
• •10. A female subject is eligible to enter the study if it is confirmed that she is:
• •a Not pregnant or nursing b Of non-childbearing potential (ie, women who have had a hysterectomy, both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 50 years of age with cessation \[for 12 months\] of previously occurring menses), or c Of childbearing potential (ie, women who have not had a hysterectomy, both ovaries removed, or no medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from 3 weeks prior to Baseline/Day 1 until 30 days after the last dose of treatment or 3 months after last dose of Ribavirin:
• •• Complete abstinence from intercourse. Periodic abstinence from intercourse (eg, calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.
• •Or
• •* Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 3 months after the last dose of Ribavirin. Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to screening may continue their contraceptive regimen in addition to the study specified methods of birth control.
• •* Intrauterine device (IUD) with a failure rate of \< 1% per year
• •* Female barrier method: cervical cap or diaphragm with spermicidal agent
• •* Tubal sterilization
• •* Vasectomy in male partner
• •11. All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of screening until 7 months after their last dose of Ribavirin :
• •• Implants of levonorgestrel
• •* Injectable progesterone
• •* Oral contraceptives (either combined or progesterone only)
• •* Contraceptive vaginal ring
• •* Transdermal contraceptive patch
• •12. Male subjects must agree to refrain from sperm donation for at least 6 months after the last dose of Ribavirin.
• •13. Subject must be of generally good health as determined by the Investigator.
• •14. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
• •1. Willing and able to provide written informed consent.
• •2. Male or female, age ≥ 18 years.
• •3. HCV genotype 4 at screening as determined by the Central Laboratory. Any non definitive results will exclude the subject from study participation. Historical result from prior participation in this study is acceptable, if applicable.
• •4. Cohort 1 only: HCV RNA ≥ 104 IU/mL at screening.
• •5. Chronic HCV infection (≥ 6 months) documented by medical history.
• •6. HCV treatment naïve, defined as no prior exposure to any IFN, Ribavirin, or other approved or experimental HCV specific direct acting antiviral agent
• •7. BMI ≥ 18 kg/m2
• •Absence of cirrhosis is defined as any one of the following:
• •a Liver biopsy within 2 years of Screening showing absence of cirrhosis b Fibroscan with a result of ≤ 12.5 kPa within 6 months of Baseline/Day1 In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above criteria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan or FibroTest.
• •8. Screening ECG without clinically significant abnormalities.
• •9. Subjects must have the following laboratory parameters at screening:
• •\- ALT ≤ 10 x the upper limit of normal (ULN)
• •\- AST ≤ 10 x ULN
• •\- Hemoglobin ≥ 12 g/dL for male, ≥ 11 g/dL for female subjects
• •\- Platelets \> 50,000 cells/mm3
• •\- INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
• •* Albumin ≥ 3 g/dL
• •* Total bilirubin ≤ 1.5 x ULN
• •* Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation Subjects who received prior treatment in this study and who currently do not fulfill all of the above requirements may be enrolled in Part B Cohort 2 at the request of the Investigator and with the approval of the Medical Monitor or Study Director.
• •10. Subject has not been treated with any investigational drug or device within 28 days of the Baseline/Day 1 visit.
• •11. A female subject is eligible to enter the study if it is confirmed that she is:
• •d Not pregnant or nursing e Of non-childbearing potential (ie, women who have had a hysterectomy, both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 50 years of age with cessation \[for 12 months\] of previously occurring menses), or f Of childbearing potential (ie, women who have not had a hysterectomy, both ovaries removed, or no medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from 3 weeks prior to Baseline/Day 1 until 30 days after the last dose of treatment or 3 months after last dose of Ribavirin:
• •• Complete abstinence from intercourse. Periodic abstinence from intercourse (eg, calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.
• •Or
• •• Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 3 months after the last dose of Ribavirin. Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to screening may continue their contraceptive regimen in addition to the study specified methods of birth control.
• •• Intrauterine device (IUD) with a failure rate of \< 1% per year
• •• Female barrier method: cervical cap or diaphragm with spermicidal agent
• •• Tubal sterilization
• •• Vasectomy in male partner
• •12. All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of screening until 7 months after their last dose of Ribavirin :
• •* Implants of levonorgestrel
• •* Injectable progesterone
• •* Oral contraceptives (either combined or progesterone only)
• •* Contraceptive vaginal ring
• •* Transdermal contraceptive patch
• •13. Male subjects must agree to refrain from sperm donation for at least 6 months after the last dose of Ribavirin.
• •14. Subject must be of generally good health as determined by the Investigator.
• •15. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.