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    Summary
    EudraCT Number:2012-001571-36
    Sponsor's Protocol Code Number:GS-US-322-0207
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-06-17
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2012-001571-36
    A.3Full title of the trial
    A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of GS-6624 in Subjects with Idiopathic Pulmonary Fibrosis (RAINIER)
    Wieloośrodkowe, randomizowane z zastosowaniem podwójnie ślepej próby i kontrolowane placebo badanie fazy II oceniające skuteczność i bezpieczeństwo stosowania preparatu GS 6624 u pacjentów z idiopatycznym włóknieniem płuc (badanie RAINIER)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate if a new drug is effective in preventing the progression of lung fibrosis
    A.3.2Name or abbreviated title of the trial where available
    RAINIER
    A.4.1Sponsor's protocol code numberGS-US-322-0207
    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 pointClinical Trial Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Buiding, Granta Park
    B.5.3.2Town/ cityAbington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441223897300
    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-6624
    D.3.4Pharmaceutical form Solution for injection
    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 INNSimtuzumab
    D.3.9.1CAS number 1318075-13-6
    D.3.9.2Current sponsor codeGS-6624
    D.3.9.3Other descriptive nameGS-6624
    D.3.9.4EV Substance CodeSUB33243
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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 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 placeboSolution for injection
    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
    Idiopathic pulmonary fibrosis
    E.1.1.1Medical condition in easily understood language
    lung fibrosis of unknown cause
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10021240
    E.1.2Term Idiopathic pulmonary fibrosis
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    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 objective of this study is:
    • To determine the effect of simtuzumab (GS-6624) on progression free survival (PFS) as determined by either a categorical decline in forced vital capacity (FVC) or all-cause mortality, in all subjects enrolled or in a subset of subjects who are classified as Lysyl Oxidase-like-2 (LOXL2) High based on a pre-specified level in serum at baseline.
    E.2.2Secondary objectives of the trial
    • Effects of simtuzumab on all-cause mortality
    • Predictive effects of baseline serum LOXL2 levels on treatment response as measured by primary and secondary endpoints
    • Effects of simtuzumab on change in lung function
    • Effects of simtuzumab on adjudicated acute exacerbations
    • Effects of simtuzumab on adjudicated respiratory hospitalizations and adjudicated deaths
    • Effects of simtuzumab on 6-minute walk distance (6MWD)
    • Effects of simtuzumab on quality of life
    • The safety and tolerability of simtuzumab
    • Exploratory objectives include evaluation of:
    • Effect of simtuzumab on degree of fibrosis on high resolution computed tomography (HRCT) scans
    • Effect of simtuzumab on sLOXL2 levels compared to placebo
    • Prognostic effects of baseline levels of sLOXL2 on disease prognosis as determined in placebo arm.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects from 45 to 85 years of age
    2. A confident diagnosis of IPF consistent with diagnostic criteria described in the 2011 American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. HRCT or surgical lung biopsy data will be interpreted by a central service. The term “surgical lung biopsy” encompasses biopsies obtained at open thoracotomy and thoracoscopy, as well as, cryobiopsies obtained through bronchcoscopy. The diagnosis of IPF must have be made within 3 years prior to screening, or if diagnosis was made > 3 years prior to screening, there must be evidence of clinical worsening within 12 months prior to screening, as judged by the investigator.
    3. 6MWD ≥ 50 meters (164 feet): use of ≤ 6L/min supplemental O2 is permitted.
    4. Able to maintain O2 saturation of ≥ 89% while breathing room air at rest at sea level. If the study site is located at more than 1000 meters above sea level, the subject must be able to maintain O2 saturation of ≥ 89% while on 2 liters of supplemental oxygen at rest (eligible subjects are permitted to use supplemental oxygen during sleep and on exertion based on the clinical judgment of the investigator, to a maximum of 6 liters/minute).
    5. Able to perform complete breath hold for diffusing lung capacity so that a carbon monoxide (DLCO) measurement can be safely undertaken
    6. Negative serum pregnancy test at screening and negative urine pregnancy test at randomization for female subjects of childbearing potential
    7. Willingness of female subjects of childbearing potential to undergo urine pregnancy tests at each study visit starting at Randomization
    8. Females of childbearing potential must agree to use highly effective methods of contraception from the screening visit throughout the study period and for 90 days following the last dose of IMP. Please refer to Section 8.11.2 for protocol recommended methods of contraception; females of childbearing potential must have negative serum β-hCG at screening
    9. Non-vasectomized male subjects must agree to use a highly effective method of contraception if sexually active with a partner who is of child bearing potential. Subjects must refrain from sperm donation from Randomization throughout the study period until 90 days following the last dose of investigational medicinal product (IMP).
    10. Lactating females must agree to discontinue nursing before enrolling in the study and for the duration of the study while receiving IMP
    11. Competency to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF); subjects must sign the form prior to the initiation of any study procedures/assessments, unless the assessment is performed as standard of
    care for this disease
    E.4Principal exclusion criteria
    1. Pregnant or breastfeeding
    2. Clinically significant respiratory diseases other than IPF, including asbestosis, other pneumoconiosis or hypersensitivity pneumonitis
    3. Obstructive lung disease determined by Pulmonary Function Test (PFTs) or HRCT as follows: - Evidence of reactive airway disease by an increase in forced expiratory volume in 1 second (FEV1) following bronchodilator challenge that exceeds both 200 ml AND exceeds a 12% increase from the prebronchodilator value OR FEV1/FVC ratio < age adjusted lower limit of normal (LLN) OR Residual volume (RV) > 120% by plethysmography (see Section 6.5 for alternative methods) OR Significant emphysema on HRCT defined as more emphysema than fibrosis interpreted by a central radiology service 4. FVC > 90%
    5. Hemoglobin corrected, not volume corrected, (DLCO) <25% of predicted normal
    6. Surgical lung biopsy (SLB) diagnostic for pneumoconiosis, hypersensitivity pneumonitis
    nonspecific interstitial pneumonia or other idiopathic interstitial lung disease
    7. Any clinically diagnosed collagen vascular disease
    8. History of aortic aneurysm ≥ 3.5cm in diameter
    9. History of cerebrovascular accident (stroke) within the preceding 26 weeks
    10. Clinically significant heart disease defined as a myocardial infarction documented by an ST
    elevation (STEMI) on electrocardiogram (ECG) within 6 months prior to screening, percutaneous coronary intervention or coronary artery bypass surgery within 6 months prior to screening, unstable angina pectoris, congestive heart failure (NYHA class III/IV or known left ventricular ejection fraction < 25%), right heart failure, significant right ventricular hypertrophy, or uncontrolled arrhythmia
    11. Require pharmaceutical treatment for pulmonary hypertension
    12. Hospitalization for acute respiratory illness < 26 weeks prior to screening, unless reviewed
    with the Medical Monitor
    13. Aspiration pneumonia < 26 weeks prior to screening
    14. Active or recent (< 4 weeks prior to Screening and/or during the screening period) respiratory
    bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) (Must not meet this criterion at time of Randomization)
    15. Active work-up for suspected lung cancer or history of cancer or
    precancerous state (eg, familial polyposis, BRCA1, BRCA2, carcinoma in-situ) within 5 years
    prior to screening except for the following: Definitive prophylactic surgery for precancerous state
    Excision of non melanomatous skin cancer treated with clear margins Prostate carcinoma treated with surgery or radiation with normal PSA for 24 months, not requiring either chemotherapy or hormone therapy
    16. History of human immunodeficiency virus (HIV), or active hepatitis C or hepatitis B infection. Subjects with hepatitis C who have had successful curative
    therapy will be eligible
    17. Co-morbid condition or illness limiting life expectancy to < 2 years at
    time of screening
    18. Major surgery, as defined by the investigator, < 30 days prior to screening. Scheduled major elective surgery during the expected duration of the study should be
    discussed with the Gilead Medical Monitor.
    19. History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator and the Gilead Medical Monitor, would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion
    20. Current excessive consumption of alcohol or use of illegal drugs as
    determined by the investigator Related to physiologic or organ specific abnormalities:
    21. Use of supplemental O2 > 6L/min during activity
    22. Inadequate organ function reflected by any of the following: Platelets < 100 x 109/L, Hemoglobin < 11.0 g/dL, Absolute Neutrophil
    Count (ANC) < 1.5 x 109/L, PT/INR and PTT > 1.5 x upper limit of normal (ULN) (except for subjects on therapeutic, anti-coagulation regimens), AST/ALT > 3 x ULN, Total bilirubin > 1.5 x ULN, Serum creatinine > 2.0 mg/dL, Related to treatment for IPF or investigational
    drugs:
    23. Treatment with immunosuppressive, cytotoxic, or antifibrotic
    drugs
    24. Oral doses of corticosteroids exceeding the equivalent of 10 mg
    prednisone per day within the 60 days prior to Screening and/or during
    the screening period
    25. Participation in an investigational drug or device trial < 30 days prior
    to Screening or within 5 times the half-life of the investigational agent in
    the other clinical study, if known
    26. Treatment with simtuzumab in another clinical study
    27. Subjects actively listed for lung transplant are excluded. However
    subjects at transplant centers with long waiting times (greater than 1
    year) may be permitted to enter the study after discussion with Medical
    Monitor to ensure that subjects are off study drug for ≥ 28 days before
    undergoing transplant surgery
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is:
    PFS among intent-to-treat (ITT) all subjects. PFS is defined as time between randomization and all-cause mortality or a categorical decrease in FVC % predicted (≥ 10% relative decrease and a ≥ 5% absolute decrease) from baseline.
    PFS in a subset of ITT subjects who are classified as LOXL2 Hign based on a pre-specified threshold level of LOXL2 in serum at baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be evaluated at every visit from randomization onwards
    E.5.2Secondary end point(s)
    Secondary endpoints are:
    • All-cause mortality as measured by overall survival among ITT
    subjects
    • All-cause mortality among subjects who are sLOXL2 High at baseline
    • Change in FVC% predicted
    Other secondary endpoints are:
    • Acute exacerbations
    • Adjudicated respiratory hospitalizations
    • Adjudicated deaths
    • Change in 6MWD
    • Change in SGRQ score
    Exploratory endpoints include:
    • Change in DLco % predicted
    • Change in HRCT findings
    • Change in sLOXL2 levels
    • Determine whether baseline sLOXL2 levels are prognostic for disease progression in placebo arm of the study
    • Evaluate the predictive effects of baseline sLOXL2 levels on various
    clinical endpoints as outlined in secondary objectives
    E.5.2.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be evaluated at every visit from randomization onwards.
    PK through serum simtuzumab levels will be measured approximately every 12 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 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 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 Yes
    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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA82
    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
    Canada
    Israel
    Korea, Republic of
    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
    Last patient, last visit.
    This study will continue until the sponsor, Gilead Sciences, or the
    principal investigator determines the drug is not beneficial or not safe
    for the subject, or the sponsor terminates the simtuzumab program, or
    until simtuzumab is available commercially.
    When at least 250 PFS events have occurred, all subjects will be given
    the opportunity of continuing in an open-label rollover extension of the
    study to monitor the safety of simtuzumab in subjects with IPF.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    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 200
    F.4.2.2In the whole clinical trial 500
    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)
    None
    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 Decision2013-09-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-05-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-01-04
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