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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   36400   clinical trials with a EudraCT protocol, of which   5997   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
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    EudraCT Number:2014-002121-35
    Sponsor's Protocol Code Number:GS-US-337-1406
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-09-16
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2014-002121-35
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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.
    A.4.1Sponsor's protocol code numberGS-US-337-1406
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGilead Sciences, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGilead Sciences Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences Inc
    B.5.2Functional name of contact pointMedical Monitor
    B.5.3 Address:
    B.5.3.1Street Address333 Lakeside Drive
    B.5.3.2Town/ cityFoster City, CA
    B.5.3.3Post code94404
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16505743000
    B.5.5Fax number+16505789264
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameLedipasvir/Sofosbuvir FDC
    D.3.2Product code GS-5885/GS-7977 FDC
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSofosbuvir
    D.3.9.1CAS number 1190307-88-0
    D.3.9.2Current sponsor codeGS-7977
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLedipasvir
    D.3.9.2Current sponsor codeGS-5885
    D.3.9.3Other descriptive nameGS-5885
    D.3.9.4EV Substance CodeSUB32080
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number90
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Genotype 1 and Genotype 4 Hepatitis C Virus Infection
    E.1.1.1Medical condition in easily understood language
    Hepatitis C Virus Infection
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10019751
    E.1.2Term Hepatitis C virus
    E.1.2System Organ Class 100000004848
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    E.2.2Secondary objectives of the trial
    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
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacogenomics (PG) Substudy

    Pharmacogenomics sub study 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
    E.3Principal 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.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ (15 IU/mL) 12 weeks after cessation of therapy) in the Full Analysis Set (FAS) population.

    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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Efficacy: 12 weeks post last treatment dose

    Safety: Continuous throughout the duration of the study
    E.5.2Secondary 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.
    E.5.2.1Timepoint(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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA5
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last Subject Last Visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 135
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 150
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Following completion of the study, subjects should be followed by their treating physician according to the local standard of care for allograph recipients. Subjects with cirrhosis should be followed for the potential development of HCC according to the local standard of care.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-10-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-07-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-06-16
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