A trial investigating the safety and efficacy of a drug combination Ledipasvir/Sofosbuvir for Subjects with hepatitis C who are on dialysis for kidney disease.

Phase 1

Conditions: Chronic Hepatitis C virus infection
MedDRA version: 20.1Level: PTClassification code 10008912Term: Chronic hepatitis CSystem Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0Level: PTClassification code 10019744Term: Hepatitis CSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2016-003489-25-IT

Lead Sponsor: GILEAD SCIENCES INCORPORATED

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 95

Inclusion Criteria

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) Chronic HCV infection (= 6 months) as documented by prior medical history or liver biopsy
4) HCV RNA = LLOQ at screening
5) Genotype 1,4, 5 and 6 HCV as determined at Screening
6) End stage renal disease (ESRD) requiring peritoneal dialysis (PD) or hemodialysis (HD)
7)he most recent HCV treatment must have been completed at least 8
weeks prior to Screening.
8) Subjects must have a determination of treatment experience (treatment naïve vs. treatment experienced). Treatment naïve is defined as having never been exposed to an approved or experimental HCV-specific direct acting antiviral agents or prior treatment of HCV with interferon or ribavirin. All other patients will be considered treatment experienced.
9) Subjects must have appropriate testing for determination of cirrhosis status.
a) Presence of cirrhosis is defined as any one of the following:
i) Fibroscan with a result of > 12.5 kPa
ii) Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score = 5)
iii) In the absence of liver biopsy or availability of Fibroscan, FibroTest® score = 0.75 at screening
b) Absence of cirrhosis is defined as any one of the following:
i) Fibroscan with a result of = 12.5 kPa within = 6 months of Baseline/Day 1
ii) Liver biopsy performed within 2 years of Screening showing absence of cirrhosis
iii) In the absence of liver biopsy or availability of Fibroscan, FibroTest® score < 0.75 at screening
10) Liver imaging within 6 months of Baseline/Day 1 is required in cirrhotic subjects only, to exclude HCC
11) Subjects with HIV-1 coinfection may be eligible, provided they satisfy these additional inclusion criteria:
i) Completed at least 3 months of any prior HIV ARV therapy and maintained HIV RNA<50 copies/mL (or 100 cells/mm3 prior to Screening. Subjects with an isolated or
unconfirmed HIV RNA >50 copies/mL (or >LLOQ if the local laboratory assay’s LLOQ
is 50= copies/mL) are not excluded ii) On a stable ARV regimen for = 8 weeks prior to Screening and is expected to continue
the current ARV regimen through the end of study.
12) A negative serum pregnancy test is required for female subjects (unless permanently sterile
or greater than two years post-menopausal).
13) 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.
14) Lactating females must agree to discontinue nursing before the study drug is administered.
15) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Current or prior history of any of the following:
a) Clinically-significant illness (other than HCV, HIV and kidney disease or co-morbidities
associated with ESRD except as noted below) any other major medical disorder that may
interfere with subject treatment, assessment or compliance with the protocol; subjects
currently under evaluation for a potentially clinically significant illness (other than HCV
or ESRD) are also excluded.
b) Current or prior history of significant cardiac disease including or resulting in:
¿ Hospital admission for significant cardiovascular disease (myocardial infarction,
unstable angina, heart failure, hypertensive emergency) or has had a cardiovascular
procedure (e.g. CABG or PTCA), within 6 months of Screening
¿ Cardiomyopathy with ejection fraction <50%
c) Gastrointestinal disorder or postoperative condition that could interfere with the
absorption of the study drug.
d) Difficulty with blood collection and/or poor venous access for the purposes of
phlebotomy.
e) Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
f) Solid organ transplantation other than failed kidney transplants (current use of =5 mg/day
of prednisone, or equivalent dose of corticosteroid, allowed).
g) Significant pulmonary disease
h) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of
their psychiatric illness within the last 2 years.
i) Malignancy within the 5 years prior to screening, with the exception of specific cancers
that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under
evaluation for possible malignancy are not eligible
2) Screening ECG with clinically significant abnormalities
3) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease,
alfa-1 antitrypsin deficiency, cholangitis).
5) Opportunistic infection (Appendix 5) within 6 months prior to Screening
6) Infection (other than HIV or HCV) requiring parenteral therapy within 30 days prior to
baseline.
7) Life threatening SAE during the screening period
8) Subjects has the following laboratory parameters at screening:
a) ALT > 10 X the upper limit of normal (ULN)
b) AST > 10 X ULN
c) Direct bilirubin > 1.5 X ULN. For subjects receiving ritonavir boosted atazanavir
regimen, a direct bilirubin > 1.5 x ULN will be allowed if < 25% of the total bilirubin
d) Platelets < 25,000/µL
e) HbA1c > 9%
f) Hemoglobin < 9 g/dL
g) Albumin < 2.8 g/dL
h) INR > 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant
regimen affecting INR
i) Hepatitis B surface antigen positive
9) Prior exposure to any HCV NS5A inhibitor.
10) Male with pregnant female partner.
11) Females who may wish to become pregnant and/or plan to undergo egg harvesting during the
course of the study and up to 30 days of the last dose of study drug
12) Males who may wish to donate sperm during the course of the study until at least 30 days
after the last dose of study drug.
13) Clinically-relevant alcohol or drug 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 must be approved by the investigator.
14) Use of any prohibited concomitant medications as described in Section 5.4.
15) Chronic use of systemically administered immunosuppressive agents (e.g., pred

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

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