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    Summary
    EudraCT Number:2016-000897-39
    Sponsor's Protocol Code Number:GS-US-373-1499
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-10-27
    Trial results View 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 ConcernedGermany - PEI
    A.2EudraCT number2016-000897-39
    A.3Full title of the trial
    Evaluation of the Efficacy and Safety of GS-5745 as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Subjects with Moderate to Severe Rheumatoid Arthritis.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An investigational study to assess the effectiveness and safety of a new investigational drug as a add-on therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate regimen in patients with moderate to severe Rheumatoid Arthritis.
    A.4.1Sponsor's protocol code numberGS-US-373-1499
    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 International Ltd.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park
    B.5.3.2Town/ cityAbington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.5Fax 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 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.3.2Product code GS-5745
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGS-5745
    D.3.9.1CAS number 1518996-49-0
    D.3.9.2Current sponsor codeGS-5745
    D.3.9.3Other descriptive nameGS-5745
    D.3.9.4EV Substance CodeSUB119675
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    D.3.11.13.1Other medicinal product typemonoclonal antibody
    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 placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of GS-5745 versus placebo as an add-on therapy to a TNF inhibitor and methotrexate in subjects with moderate to severe rheumatoid arthritis Rheumatoid Arthritis.
    E.2.2Secondary objectives of the trial
    To assess the safety and tolerability of GS-5745 versus placebo as an add-on therapy with a TNF inhibitor and methotrexate in subjects with moderate to severe Rheumatoid Arthritis.
    To assess the pharmacokinetics (PK) of GS-5745 as an add-on therapy with a TNF inhibitor and methotrexate in subjects with moderate to severe Rheumatoid Arthritis.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Optional PK sub-study
    E.3Principal inclusion criteria
    Subjects must meet all of the following inclusion criteria to be eligible for participation in this
    study.
    1) Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of the study procedures; subjects who need a representative/guardian to provide consent are not permitted in this study
    2) Male or female subjects between 18 and 80 years of age inclusive, at time of signing initial informed consent
    3) Diagnosis of RA according to the 2010 ACR/EULAR classification criteria (See Appendix 8), confirmed at Screening
    4) Subjects must meet Class I, II, or III of the ACR 1991 Revised Criteria for Global Functional Status in RA (Appendix 6), at Screening
    5) Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to the first dose of study drug
    6) Must have ≥ 12 weeks of ongoing treatment with an approved, SC formulation of TNF inhibitor (adalimumab, certolizumab, etanercept, or golimumab, or marketed biosimilar TNF inhibitor), with at least 6 weeks of stable dose (defined as no change in prescription) defined as:
    7) Subjects who have previously received other biologic DMARDs for the treatment of RA are eligible, providing the following washout periods for these have been met:
    - Rituximab – none for at least 6 months prior to Baseline and subject has a CD19+ B cell count in normal range (per central lab) at Screening
    - Infliximab – none for at least 8 weeks prior to Baseline
    - Tocilizumab – none for at least 8 weeks prior to Baseline
    8) Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to Baseline are allowed and should be continued at the same stable dose throughout the blinded period of the study; PRN NSAIDs for indications other than RA are also allowed.
    9) TB Screening: Subjects must meet either a. or b.:
    a. A negative history of TB infection and a negative QuantiFERON® TB-Gold In-Tube test and chest x-ray results (see below). QuantiFERON® tests with inconclusive results may be repeated one time. If the repeat result is also is inconclusive, the subject will be excluded from the study.
    OR,
    b. Subjects with a history of latent TB treated with a full course of prophylaxis as per local guidelines, are allowed per investigator judgment.
    10) A negative chest x-ray (views per local guidelines) for active TB or other lung disease at Screening; or a chest x-ray within 90 days of Screening if films or report are available for investigator review
    11) A negative pregnancy test is required for female subjects of childbearing potential (as defined per protocol), at Screening and at Day 1, prior to dosing of study drug. Female subjects must agree not to become pregnant for 30 days after the last dose of GS-5745
    12) Subjects of child-bearing potential (as defined in protocol) must agree to use protocol specified contraceptive measures throughout the study and for 30 days after their last dose of study drug. Female subjects must agree not to become pregnant for 30 days after the last dose of study drug. Male and female subjects taking methotrexate or other drugs should also follow contraception guidelines in the relevant product local label
    13) Lactating females must agree to discontinue breastfeeding prior to dosing of study drug and for the duration of the study.
    E.4Principal exclusion criteria
    1) Current treatment with any disease modifying anti-rheumatic drug (DMARD) other than MTX, chloroquine or hydroxychloroquine, or current treatment with other immune modulating/suppressive non-biologic and biologic medications
    2) Intra-articular corticosteroid injection within 4 weeks of Baseline
    3) Any infection requiring oral antimicrobial therapy within 2 weeks prior to Baseline.
    4) Previous treatment with GS-5745; known hypersensitivity to GS-5745 or its formulation excipients.
    5) Known hypersensitivity to the TNF inhibitor or its formulation excipients that the subject is receiving at Screening
    6) Any live or attenuated vaccines within 4 weeks prior to the first dose of study drug or plan to be vaccinated with these vaccines at any time during the study or within 12 weeks after the last dose of study drug.
    7) Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication; (subjects with Sjogren’s syndrome or controlled thyroiditis as defined by the investigator are not excluded)
    8) Active systemic involvement secondary to RA such as vasculitis or Felty’s syndrome
    9) History of any of the following within 12 months of Baseline:
    a) infection requiring parenteral antibiotics or hospitalization,
    b) any life-threatening infection,
    c) sepsis
    10) History of infected prosthetic joint at any time, with the prosthesis still in situ
    11) Significant blood loss (>450 mL) or transfusion of blood product within 12 weeks prior to Day 1.
    12) The results of the following laboratory tests (hemoglobin, white blood cells, neutrophils, lymphocytes, platelets, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), total bilirubin level, estimated glomerular filtration rate, positive HIV serology, evidence of active Hepatitis B, evidence of active Hepatitis C, any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study), performed at the central laboratory at Screening meet any of the protocol criteria)
    13) Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study, per judgment of investigator
    14) Current malignancy, or a history of malignancy or lymphoproliferative disorder within 10 years of Screening, except:
    a) Carcinoma in situ of the cervix that has been successfully treated
    b) Basal or squamous cell cancer or other localized non-melanoma skin cancer that has been successfully treated
    15) Participation in another investigational drug study within 1 month of Screening (for a small molecule) or within 3 months or 5 drug half-lives prior to Screening, whichever is longer (for a biologic agent)
    16) Male subjects who are unwilling to refrain from sperm donation during the study and for 90 days after their last dose of study drug
    17) Female subjects who are unwilling to refrain from egg donation or egg harvesting (for the purpose of current or future fertilization) during the course of the study for 30 days after their last dose of study drug and
    18) Presence of any condition that could, in the opinion of the investigator, compromise the subject’s ability to participate in the study, eg, substance abuse, alcoholism, or an unstable psychiatric condition.
    19) Known hypersensitivity to rubber or latex
    20) Have undergone surgical treatments for RA including synovectomy or arthroplasty within the last 12 weeks prior to Screening or planned such surgery during the study
    21) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia, or a new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participating in the study.
    22) Any chronic, uncontrolled medical condition which would put the subject at increased risk during the study, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease of concern, as per judgment of the investigator.

    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study includes:
    - Change in DAS28(CRP) from Baseline to Week 12
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to week 12
    E.5.2Secondary end point(s)
    The secondary endpoints of this study include:
    - Proportion of subjects that achieve DAS28(CRP) ≤ 3.2 at Week 12
    - Proportion of subjects that achieve DAS28(CRP) < 2.6 at Week 12
    - Assess plasma concentrations of GS-5745
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12
    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 Yes
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    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
    Australia
    Belgium
    Germany
    Hungary
    Mexico
    Taiwan
    United States
    E.8.7Trial has a data monitoring committee Yes
    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 years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days13
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days13
    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: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 13
    F.4.2.2In the whole clinical trial 75
    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)
    After a patient has completed/terminated their study participation, long term care for the participant will remain the responsibility of their primary treating physicians.
    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 Decision2017-02-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-10
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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