Overview
Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Tablet Plus Ribavirin Tablet (Part A) Versus Single Dose (2 Tablets) of EHCV Containing Sofosbuvir, Ribavirin, and Natural Anti-hemolytic (B) in Egyptian Adults With Chr
Status:
Completed
Completed
Trial end date:
1969-12-31
1969-12-31
Target enrollment:
0
0
Participant gender:
All
All
Summary
Two Groups of Genotype 4 HCV Patients will participate through open-label randomized Study comparing Sofosbuvir tablet Plus Ribavirin tablet (Part A) versus single Dose (2 tablets) of EHCV containing Sofosbuvir, Ribavirin, and Natural anti-hemolytic (B) evaluating the safety and efficacy for both arms. Sponsor: Wadi El Nil Hospital Study Centers Planned: Approximately 2 sites in EgyptPhase:
Phase 2/Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Egyptian Liver HospitalCollaborator:
Wadi El Nil HospitalTreatments:
Ribavirin
Sofosbuvir
Criteria
Inclusion CriteriaInclusion Criteria for Part A
Subjects must meet all of the following inclusion criteria to be eligible for participation
in this study.
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, or
5. HCV genotype 4 at screening as determined by the Central Laboratory. Any
non-definitive results will exclude the subject from study participation.
6. The subject's medical records must be sufficient to categorize prior treatment history
as one of the following:
i) IFN-intolerant: subject had documented intolerance to IFN during prior IFN therapy
of up to 12 weeks duration ii) Non-response: subject did not achieve undetectable HCV
RNA levels on treatment iii) Relapse/Breakthrough: subject achieved undetectable HCV
RNA levels during treatment or within 4 weeks after treatment and later showed
detectable HCV RNA
An Absence of cirrhosis is defined as any one of the following:
- Liver biopsy within 2 years of Screening showing absence of cirrhosis
- Fibroscan with a result of ≤ 12.5 kPa within 6 months of Baseline/Day1
- FibroTest score of ≤ 0.48 AND APRI of ≤ 1 performed during Screening 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 Fibro Test.
7. Body mass index (BMI) ≥ 18 kg/m2.
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
- Direct bilirubin ≤ 1.5 x ULN
- HbA1c ≤ 10%
- Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault
equation
10. Subject has not been treated with any investigational drug or device within 30 days of
the screening visit.
11. A female subject is eligible to enter the study if it is confirmed that she is:
1. Not pregnant or nursing
2. 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
3. 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 6 months
after last dose of RBV:
- 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 6 months after the last dose of RBV. 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 RBV:
- 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 7 months after
the last dose of RBV.
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.
Inclusion Criteria for Part B
Subjects must meet all of the following inclusion criteria to be eligible for participation
in this study.
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. Cohort 1 only: HCV treatment naïve, defined as no prior exposure to any IFN, RBV, 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:
1. Liver biopsy within 2 years of Screening showing absence of cirrhosis
2. Fibroscan with a result of ≤ 12.5 kPa within 6 months of Baseline/Day1 C- Fibro
Test score of ≤ 0.48 AND APRI of ≤ 1 performed during Screening
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 Fibro Test.
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
- Direct bilirubin ≤ 1.5 x ULN
- HbA1c ≤ 10%
- 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
LDV/SOF or 6 months after last dose of RBV:
• 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 30 days after the last dose of LDV/SOF or 6 months after the last
dose of RBV.
- 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
- Implants of levonorgestrel
- Injectable progesterone
- Oral contraceptives (either combined or progesterone only)
- Contraceptive vaginal ring
- Transdermal contraceptive patch
12. All male study participants must agree to consistently and correctly use a condom from
Baseline until 90 days after their last dose of LDV/SOF or 7 months after their last
dose of RBV. If their female partner is of childbearing potential (as defined above),
she must use 1 of the methods of birth control listed above from the date of screening
until 90 days after their last dose of LDV/SOF or 7 months after their last dose of
RBV.
13. Male subjects must agree to refrain from sperm donation for at least 7 months after
the last dose of RBV or 90 days after their last dose of LDV/SOF, as applicable.
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.
Exclusion Criteria
Exclusion Criteria for Part A
Subjects who meet any of the following exclusion criteria are not to be enrolled in this
study.
1. for treatment naïve subjects only: Prior exposure to IFN, RBV, or other approved or
experimental direct-acting antiviral targeting the HCV.
2. for treatment-experienced subjects: prior exposure to a NS5a inhibitor, NS5b
nucleotide inhibitor, or NS5b non-nucleotide inhibitor targeting the HCV
3. Pregnant or nursing female or male with pregnant female partner.
4. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1
antitrypsin deficiency, cholangitis).
5. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
6. Contraindication to RBV therapy e.g., history of clinically significant
hemoglobinopathy (sickle cell disease, thalassemia).
7. History of 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 screening); subjects under
evaluation for malignancy are not eligible.
8. Chronic use of systemically administered immunosuppressive agents (eg, prednisone
equivalent > 10 mg/day).
9. Clinically-relevant drug or alcohol abuse within 12 months of screening. A positive
drug screen will exclude subjects unless it can be explained by a prescribed
medication; the diagnosis and prescription should be approved by the investigator.
10. History of solid organ transplantation.
11. Current or prior history of clinical hepatic decompensation (eg, ascites, variceal
hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary
syndrome).
12. History of clinically-significant illness or any other major medical disorder that may
interfere with subject treatment, assessment or compliance with the protocol.
13. History of a gastrointestinal disorder (or post-operative condition) that could
interfere with the absorption of the study drug.
14. History of significant pulmonary disease, significant cardiac disease or porphyria.
15. Excessive alcohol ingestion, defined as 3 glasses/day (1 glass is equivalent to 284 mL
beer, 125 mL wine, or 25 mL distilled spirits) for females and 4 glasses/day for
males.
16. History of difficulty with blood collection and/or poor venous access for the purposes
of phlebotomy.
17. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1.
18. Known hypersensitivity to RBV, the study investigational medicinal product, the
metabolites, or formulation excipients.
Exclusion Criteria for Part B
Subjects who meet any of the following exclusion criteria are not to be enrolled in this
study.
1. For treatment naïve subjects only (Cohort 1): Prior exposure to IFN, RBV, or other
approved or experimental direct-acting antiviral targeting the HCV.
2. Current or prior history of any of the following:
A Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage)
B Clinically-significant illness (other than HCV) or any other major medical disorder
that may interfere with subject treatment, assessment or compliance with the protocol,
or, current evaluation for a potentially clinically significant illness (other than
HCV) C Gastrointestinal disorder or post-operative condition that could interfere with
the absorption of the study drug D Solid organ transplantation E Significant pulmonary
disease, significant cardiac disease or porphyria F Psychiatric hospitalization,
suicide attempt, and/or a period of disability as a result of their psychiatric
illness within the last 5 years Subjects with psychiatric illness (without the prior
mentioned conditions) that is well-controlled on a stable treatment regimen for at
least 6 months prior to Baseline/Day 1 or that has not required medication in the last
12 months may be enrolled.
G Any malignancy within the 5 years prior to screening, with the exception of specific
cancers that are cured by surgical resection (basal cell skin cancer, etc.), or
current evaluation for possible malignancy H Difficulty with blood collection and/or
poor venous access for the purposes of phlebotomy I Significant drug allergy (such as
anaphylaxis or hepatotoxicity)
3. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, α1
antitrypsin deficiency, cholangitis)
4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
5. Use of any prohibited concomitant medications
6. Contraindication to RBV therapy, including significant history of clinically
significant hemoglobinopathy (eg, sickle cell disease, thalassemia)
7. In the judgment of the investigatory, any clinically-relevant drug or alcohol abuse
within 12 months of screening that may interfere with subject treatment, assessment of
compliance with the protocol
8. Pregnant or nursing females or male with pregnant female partner
9. Known hypersensitivity to RBV, SOF, or formulation excipients