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 kidney transplantation.

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2014-002121-35-AT
• Date of registration: 18/09/2014
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: 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 kidney transplantation.
• Scientific title: A Phase 2, Open Label Study to Evaluate The Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) Tablet for 12 or 24 Weeks in Kidney Transplant Recipients with Chronic HCV Infection
• Date of first enrolment: 26/09/2014
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002121-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany

Contacts

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc

Key inclusion & exclusion criteria

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) Body mass index (BMI) = 18 kg/m2
4) Have received a kidney transplant more than 6 months before the Baseline visit
5) HCV RNA = the lower limit of quantitation (15 IU/mL) at Screening
6) HCV genotype 1 or 4 at Screening as determined by the Central Laboratory. Any non definitive results will exclude the subject from study participation.
7) Chronic HCV infection (= 6 months) documented by prior medical history or liver biopsy
1) HCV treatment status of one of the following:
a) HCV Treatment-naïve: No prior exposure to any IFN, RBV, or other approved or experimental HCV-specific DAA agent
b) HCV Treatment-Intolerant: Subjects that discontinued HCV treatment due to development or significant worsening of a treatment related adverse event
c) HCV Treatment-Experienced: Virologic failure during or after treatment. Subjects in this category must not have discontinued prior therapy due to an adverse event.
8) Have demonstrated absence of cirrhosis or have compensated cirrhosis:
a) Cirrhosis is defined as any one of the following:
i) Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score = 5)
ii) Fibroscan® (in countries where locally approved) showing cirrhosis or results > 12.5 kPa
iii) FibroTest® score of > 0.75 AND an AST: platelet ratio index (APRI) of > 2 during Screening
b) Absence of cirrhosis is defined as no evidence of cirrhosis and any one of the following:
i) Liver biopsy within 2 years of Screening showing absence of cirrhosis
ii) Fibroscan® (in countries where locally approved) within 6 months of Baseline/Day 1 with a result of = 12.5 kPa
iii) FibroTest® score of = 0.48 AND APRI of = 1 during Screening
9) Liver imaging within 6 months prior to Baseline/Day 1 is required in subjects with cirrhosis to exclude hepatocellular carcinoma (HCC)
10) Screening ECG without clinically significant abnormalities
11) Subjects must have 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
d) Platelets > 50,000 cells/µL
e) HbA1c = 10%
f) Creatinine clearance (CLcr) = 40 mL /min, as calculated by the Cockcroft Gault equation {2202}
g) Hemoglobin = 10 g/dL
h) Albumin = 3g/dL
i) INR = 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.
12) Females of childbearing potential (as defined in Appendix 4) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to enrollment.
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) Male subjects must agree to refrain from sperm donation from the date of screening until 90 days after their last dose of study drug.
15) Subject must be of generally good health, with the exception of chronic HCV infection and renal disease, as determined by the Investigator.
16) 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.
Are the trial subjects under 18? no
Number of subjects for this
Exclusion criteria:
Subjects who meet any of the following exclusion criteria will not to be eligible for participation in this study.
1) Current or prior history of any of the following:
a) Clinically-significant illness (other than HCV and kidney disease) or 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) are also excluded.
b) Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
c) Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
d) Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). The presence of varices will be accepted
e) Solid organ transplantation other than kidney.
f) Significant cardiac disease.
g) Psychiatric hospitalization and/or suicide attempt within the last 2 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 enrollment or has not required medication in the last 6 months may be included.
h) Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible.
i) Significant drug allergy (such as anaphylaxis or hepatotoxicity).
2) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
3) Pregnant or nursing female or male with pregnant female partner.
4) Chronic liver disease of a non HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha 1 antitrypsin deficiency, cholangitis).
5) In the opinion of the Investigator, clinically-relevant alcohol or drug abuse within 12 months of Screening. A positive drug screen during Screening will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the Investigator.
6) Planned or anticipated second kidney transplant.
7) Use of any prohibited concomitant medications as described in Section 5.4 .
8) Known hypersensitivity to LDV, SOF, or formulation excipients.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Genotype 1 and Genotype 4 Hepatitis C Virus Infection
MedDRA version: 18.1 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Ledipasvir/Sofosbuvir FDC
Product Code: GS-5885/GS-7977 FDC
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sofosbuvir
CAS Number: 1190307-88-0
Current Sponsor code: GS-7977
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
INN or Proposed INN: Ledipasvir
Current Sponsor code: GS-5885
Other descriptive name: GS-5885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-

Primary Outcome(s)

Main Objective: The primary objectives of this study are as follows:
• To determine the antiviral efficacy of LDV/SOF FDC as measured by the proportion of subjects who attain SVR at 12 weeks after discontinuation of therapy (SVR12)
• To evaluate the safety and tolerability of each treatment regimen as assessed by review of the accumulated safety data

Primary end point(s): The primary efficacy endpoint is SVR12 (HCV RNA
The primary safety endpoint is any AE leading to permanent discontinuation of study drug. The proportion of subjects with eGFR < 30 mL/min during study will be also evaluated. Safety endpoints will be summarized by treatment arms as the number (proportion) of subjects with events or abnormalities for categorical data or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data.

Timepoint(s) of evaluation of this end point: Efficacy: 12 weeks post last treatment dose

Safety: Continuous throughout the duration of the study

Secondary Objective: The secondary objectives of this study are as follows:
• To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
• To evaluate the emergence of viral resistance to SOF and LDV during treatment and after treatment discontinuation
• To characterize steady state pharmacokinetics (PK) of study drug
• To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)

The exploratory objectives of this study are:
• To identify or validate genetic markers that may be predictive of the natural history of disease, response to therapy and/or tolerability of medical therapies through genetic discovery research (e.g., pharmacogenomics), in subjects who provide their separate and specific consent

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints will be assessed at 4 and 24 weeks following therapy

On treatment assessments will be conduced at screening, Day-1, Week 1, 2, 4, 8, 12, 16 and 24
Post treatment visits will occur at Weeks 4, 12 and 24 post treatment

Secondary end point(s): Secondary efficacy endpoints include the proportion of subjects with HCV RNA < LLOQ at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24), and the proportion of subjects with virologic failure.

Additional efficacy evaluations may include HCV RNA change from Baseline/Day 1, ALT normalization and viral kinetic parameters.

Secondary ID(s)

GS-US-337-1406

2014-002121-35-DE

Source(s) of Monetary Support

Gilead Sciences Inc