An international study to assess the safety and efficacy of a combination of new investigational drugs in hepatitis C virus infected patients with advanced liver disease or require treatment after liver transplantation.
- Conditions
- MedDRA version: 18.1Level: LLTClassification code 10019751Term: Hepatitis C virusSystem Organ Class: 100000004848Chronic Genotype 1 and Genotype 4 Hepatitis C Virus InfectionTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2013-002802-30-NL
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
1. Willing and able to provide written informed consent or for those subjects where hepatic encephalopathy affects their ability to provide initial or ongoing consent, has an appropriate and legally-authorized representative (LAR) willing and able to provide consent on behalf of the subject.
2. Male or female, Age > or = 18 years
3. Chronic genotype 1 and 4
4. HCV RNA infection with quantifiable virus at Screening
5. Confirmation of chronic (non-acute) HCV infection 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 Day 1 visit, or
b. A liver biopsy performed prior to the Day 1 visit with evidence of chronic HCV
infection.
6. Screening ECG without clinically significant abnormalities.
7. Negative serum pregnancy test for female subjects (unless surgically sterile or greater
than two years post-menopausal; please see Appendix 4).
8. Male subjects and female subjects of childbearing potential who engage in heterosexual
intercourse must agree to use protocol specified method(s) of contraception as described
in Appendix 4.
9. Lactating females must agree to discontinue nursing before the study drugs are
administered
10. Subject must be able to comply with the dosing instructions for study drug administration
and able to complete the study schedule of assessments, including all required
post-treatment visits.
11. Ability to determine the presence/absence of cirrhosis for all groups except Cohort B,
Group 7 (which may or may not have cirrhosis)
a. Cirrhosis is defined as any one of the following:
• Liver biopsy showing cirrhosis
• Fibroscan (in countries where locally approved) showing cirrhosis or results > 12.5 kPa
• A FibroTest® score of >0.75 AND an AST:Platelet Ratio Index (APRI) of
>2 performed during screening
b. Absence of cirrhosis is defined as any one of the following:
• Liver biopsy within 2 years of Screening showing absence of cirrhosis
• Fibroscan (in countries where locally approved) with a result of = 12.5 kPa within = 6 months of Baseline/Day1
• A FibroTest® score of = 0.48 AND APRI of = 1 performed during Screening In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required; liver biopsy results will supersede blood test results and be considered definitive.
Inclusion Criteria Exclusively for Cohort A
12. Has never received a liver transplant, and if listed for transplant, expected to be at least 12 weeks prior to transplant (from anticipated Day 1 of dosing). The subject may be a candidate for a living donor transplant, as long as it is anticipated to be at least 12 weeks before the transplant surgery will occur.
Inclusion Criteria Exclusively for Cohort B, all Groups
13. Post-liver transplant (primary or secondary, cadaveric or living donor), at least 3 months since transplant procedure for all groups except Cohort B, Group 4, which must be at least 2 months since the transplant procedure).
14. Subjects may be on the waiting list for a second or third transplant. Subjects who are on the waiting list for a liver transplant must be waiting to receive an HCV negative organ.
Inclusion Criteria Exclusively for Cohort B, Group 7 (FCH) only
15. Subject must be within 18 months of transplant at screening
16. Histological evidence of fibrosing cholestatic hepatitis on post-transplant liver biopsy performed within 6 months of scree
1. Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance
2. HIV infection or chronic hepatitis B virus (HBV) infection (HBsAg positive)
3. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
4. Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
5. Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the last
6 months or during screening
6. Current malignancy (with exception of certain resolved skin cancers or other early cancer for which surgical resection is considered to be completely curative), including hepatocellular carcinoma
7. Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
8. Any prior exposure to an HCV NS5a specific inhibitor
9. Use of GM-CSF, epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of Screening
10. History of clinically significant medical condition associated with other chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson’s disease, a-1-antitrypsin deficiency, alcoholic liver disease, non-alcoholic steatohepatitis, or toxin exposures) that may affect the ability to respond to HCV therapy.
11. Active spontaneous bacterial peritonitis at screening
12. Hematological and biochemical parameters, including:
a. Hemoglobin (Hb) < 10 g/dL
b. Platelets = 30,000/ mm3
c. ALT, AST, or alkaline phosphatase = 10 ULN, sodium <125 mmol/L
d. Total bilirubin > 10mg/dL (except for the FCH cohort)
e. Serum creatinine > 2.5x upper limit of normal and/or evidence of renal impairment (CrCl < 40 mL/min).
13. Infection requiring systemic antibiotics at the time of screening
14. Participation in a clinical study with an investigational drug or biologic within 1 month prior to screening visit, unless information on the investigational drug is available to indicate that there is no potential drug interaction (safety or efficacy)
15. Active or recent history (= 6 months) of drug or alcohol abuse
16. Any contraindication to RBV therapy, per the approved package insert
17. Any history of organ transplant other than liver or kidney
18. Any medications from Section 5.4 prohibited from used within 28 days prior to the Day 1 visit through the end of treatment
19. Known hypersensitivity to RBV, LDV, SOF, or formulation excipients.
Exclusion criteria Exclusively for Cohort A subjects:
20. Medical justification for any MELD exception points (for HCC, current hepatopulmonary syndrome, intractable encephalopathy, or any other reason)
21. History of hepatopulmonary syndrome
22. Chronic use of systemic immunosuppressive agents (for autoimmune diseases, etc)
Exclusion Criteria Exclusively for Cohort B, all Groups:
23. Current use of corticosteroids at any dose > 10 mg of prednisone/day (or equivalent dose of other corticosteroid)
24. Histological evidence of unresolved rejection requiring treatment or expected to require treatment during the study period
25. Use or planned use of T-cell depleting/masking antibodies, systemic antineoplastic agents, or cyclosporine at a dose of > 300 mg/day
26. Subjects with a Child-Pugh Score of 13-15, due to the serious medical condition and poor prognosis for these patients
Exclusion criterio
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