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    Summary
    EudraCT Number:2016-002446-23
    Sponsor's Protocol Code Number:GS-US-342-1143
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-11-01
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2016-002446-23
    A.3Full title of the trial
    A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir in Adolescents and Children with Chronic HCV Infection
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial investigating the safety and efficacy of a drug combination Sofosbuvir/Velpatasvir for Adolescents and Children with hepatitis C
    A.4.1Sponsor's protocol code numberGS-US-342-1143
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/099/2015
    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 International Ltd.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressGranta Park
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441223897284
    B.5.6E-mailclinical.trials@gilead.com
    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 Yes
    D.2.1.1.1Trade name Epclusa 400 mg/100 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameEpclusa
    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.3.9.3Other descriptive nameSOFOSBUVIR
    D.3.9.4EV Substance CodeSUB121170
    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 INNVELPATASVIR
    D.3.9.2Current sponsor codeGS-5816
    D.3.9.4EV Substance CodeSUB180213
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 2
    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 nameSofosbuvir/Velpatasvir
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Yes
    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.3.9.3Other descriptive nameSOFOSBUVIR
    D.3.9.4EV Substance CodeSUB121170
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVELPATASVIR
    D.3.9.2Current sponsor codeGS-5816
    D.3.9.4EV Substance CodeSUB180213
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 3
    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 nameSOF/VEL FDC
    D.3.4Pharmaceutical form Granules in sachet
    D.3.4.1Specific paediatric formulation Yes
    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.3.9.3Other descriptive nameSOFOSBUVIR
    D.3.9.4EV Substance CodeSUB121170
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Hepatitis C virus infection
    E.1.1.1Medical condition in easily understood language
    Hepatitis C
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10019744
    E.1.2Term Hepatitis C
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10008912
    E.1.2Term Chronic hepatitis C
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    PK Lead-in phase is: To evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir/velpatasvir (SOF/VEL) in pediatric subjects with chronic hepatitis C virus (HCV) infection

    Treatment Phase is: To evaluate the safety and tolerability of SOF/VEL for 12 weeks in paediatric subjects with chronic HCV
    E.2.2Secondary objectives of the trial
    PK Lead-in Phase is: To evaluate the safety, tolerability, and antiviral activity of 7 days of dosing of SOF/VEL in
    paediatric subjects with chronic HCV

    Treatment Phase is: Determine the efficacy of SOF/VEL for 12 weeks in paediatric subjects with chronic HCV infection, as assessed by the proportion of subjects with SVR 12 weeks after cessation of treatment; Determine the proportion of subjects with SVR 4 and 24 weeks; Evaluate the proportion of subjects with virologic failure; Evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment; Evaluate the emergence of viral resistance to SOF and VEL during treatment and after cessation of treatment; Evaluate the effect of treatment with SOF/VEL on QoL; Evaluate the effect of SOF/VEL on growth and development of paediatric subjects during and after treatment; Evaluate the acceptability, including palatability, of formulations used
    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 substudy: In consenting subjects, a blood sample will be drawn at Day 1 visit. If not obtained at Day 1 visit, the sample may be drawn at any time during the 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.

    An Optional Intensive Pharmacokinetics (PK) Substudy for adolescent subjects 12 to < 18 years of age enrolled in the Treatment Phase was added at Week 4 or 8 to support population PK model development.
    E.3Principal inclusion criteria
    1) Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements. Subjects will provide assent if possible, in accordance with IRB/IEC/local requirements and the Investigator’s discretion.
    2) 3 years to < 18 years of age as determined at Day 1
    3) Chronic HCV-infection (≥ 6 months) as documented by prior medical history or liver biopsy
    4) HCV RNA ≥ 1000 IU/mL at Screening
    5) Subjects must have a determination of prior treatment status:
    a) 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.
    b) Treatment-experienced is defined as prior treatment failure or intolerance to a regimen containing interferon with or without RBV and with or without a protease inhibitor that was completed at least 8 weeks prior to Day 1.
    c) Interferon intolerant: Subject who discontinued therapy (≤ 12 weeks total) due to ≥ 1 adverse event
    6) A negative serum pregnancy test is required at screening and a negative urine test is required at Day 1 for female subjects of child bearing potential.
    7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
    8) Lactating females must agree to discontinue nursing before the IMP is administered.
    9) Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments.
    E.4Principal exclusion criteria
    1) Prior use of an HCV NS5A inhibitor
    2) Current or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)
    3) Any of the following laboratory parameters at screening: a) INR > 1.2 x ULN b) Platelets < 50,000/mm3 c) albumin < 3.5 g/dL d) ALT > 10 x the upper limit of normal (ULN) e) AST > 10 x ULN f) Direct bilirubin > 1.5 x ULN g) Estimated glomerular filtration rate < 90 mL/min/1.73m2, as calculated by the Schwartz Formula
    4) Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency)
    5) Evidence of hepatocellular carcinoma (HCC) or other malignancy (with the exception of certain resolved skin cancers)
    6) Co-infection with HIV, acute HAV, or HBV (Hepatitis B Surface Ag positive at screening)
    7) Current or prior history of any of the following:
    a) Significant cardiovascular, pulmonary, or neurological disease
    b) Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
    c) History of solid organ or bone marrow transplantation
    d) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years.
    8) Clinically-relevant alcohol or drug abuse within 12 months of screening.
    9) Sexually-active males or females of childbearing potential who are not willing to use an effective method of contraception during the study
    10) Use of any prohibited concomitant medications
    11) Investigational agents taken within the past 28 days (except with the express approval of the Sponsor)
    12) Known hypersensitivity to the study drug, the metabolites, or formulation excipients.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the PK Lead-in Phase is to determine steady-state PK, is AUCtau of VEL, SOF, and its major metabolite (GS-331007).
    The primary endpoint of the Treatment Phase is assessment of any AEs with a focus on AEs that lead to discontinuation of study drug.
    E.5.1.1Timepoint(s) of evaluation of this end point
    PK lead in phase - Day 7
    Treatment phase - SVR 12 weeks
    E.5.2Secondary end point(s)
    The secondary endpoints of the PK Lead-in Phase are:
    - Antiviral activity measurements, including assessment of HCV RNA from baseline through Day 7.
    - Any AE leading to permanent discontinuation of study drug.
    The secondary endpoints of the Treatment Phase are:
    - The proportion of subjects with sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12). SVR12 is the key efficacy endpoint.
    - The proportion of subjects with HCV RNA < LLOQ at 4 or 24 weeks after cessation of treatment (SVR4 and SVR24).
    - The proportion of subjects with virologic failure, including breakthrough/nonresponse and relapse
    - The proportion of subjects with HCV RNA < LLOQ on treatment
    - Emergence of viral resistance to SOF and /or VEL during treatment and treatment is discontinued
    - HCV RNA change from Baseline/Day 1
    - Quality of life endpoints and neuropsychiatric assessments as measured by PedsQL™ Pediatric Quality of Life survey
    - Growth and development measurements including height and weight percentiles, Tanner Stage, parental height, and bone age
    - Acceptability assessed by swallowability and palatability
    E.5.2.1Timepoint(s) of evaluation of this end point
    SVR 4, 12 and 24 weeks
    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 No
    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.7.1.3.1Other 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 trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    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 Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Italy
    United Kingdom
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    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 Yes
    F.1.1Number of subjects for this age range: 200
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 100
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 100
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 200
    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)
    All subjects (those who attain SVR24 or those who do not attain SVR24) who do not initiate other experimental or approved anti-HCV therapy will be eligible to participate in the Pediatric registry Study. The pediatric registry study is described in a separate protocol (GS-US-334-1113). This follow-up study will continue for 5 years.
    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 Decision2016-11-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-01-19
    P. End of Trial
    P.End of Trial StatusOngoing
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