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    Summary
    EudraCT Number:2019-001004-37
    Sponsor's Protocol Code Number:CRTH258B2305
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-05-29
    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 ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2019-001004-37
    A.3Full title of the trial
    A 12-Month, 2-Arm, Randomized, Double-Masked, Multicenter Phase III Study Assessing the Efficacy and Safety of Brolucizumab every 4 weeks versus Aflibercept every 4 weeks in Adult Patients with Visual Impairment due to Diabetic Macular Edema (KINGFISHER)
    Randomizované, dvojito maskované, multicentrické, 12 mesačné klinické skúšanie fázy III v dvoch skupinách na zhodnotenie účinnosti a bezpečnosti brolucizumabu v porovnaní s afliberceptom podávaných každé 4 týždne u dospelých pacientov s poruchou zraku v dôsledku diabetického edému makuly (KINGFISHER)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study assessing the efficacy and safety of Brolucizumab versus Aflibercept in patients with impaired vision due to diabetic macular oedema
    A.4.1Sponsor's protocol code numberCRTH258B2305
    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 SponsorNovartis Pharma AG
    B.1.3.4CountrySwitzerland
    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 supportNovartis Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Slovakia s.r.o.
    B.5.2Functional name of contact pointDRA information desk
    B.5.3 Address:
    B.5.3.1Street AddressŽižkova 22/B
    B.5.3.2Town/ cityBratislava
    B.5.3.3Post codeSK-811 02 
    B.5.3.4CountrySlovakia
    B.5.4Telephone number+421 2 50706116
    B.5.5Fax number+421 2 50706100
    B.5.6E-maildra.slovakia@novartis.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 Beovu
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    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.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravitreal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBROLUCIZUMAB
    D.3.9.1CAS number 1531589-13-5
    D.3.9.2Current sponsor codeRTH258 / ESBA1008
    D.3.9.3Other descriptive nameAnti-VEGF monoclonal antibody
    D.3.9.4EV Substance CodeSUB180753
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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 Yes
    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 RoleComparator
    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 Eylea
    D.2.1.1.2Name of the Marketing Authorisation holderBayer Pharma AG
    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.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravitreal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNaflibercept
    D.3.9.1CAS number 862111-32-8
    D.3.9.3Other descriptive nameAFLIBERCEPT
    D.3.9.4EV Substance CodeSUB26987
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 Yes
    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
    Diabetic Macular Edema
    E.1.1.1Medical condition in easily understood language
    Diabetic Macular Edema
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10057934
    E.1.2Term Diabetic macular edema
    E.1.2System Organ Class 100000004853
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate that brolucizumab is non-inferior to aflibercept with respect to the change in visual acuity from baseline up to week 52
    E.2.2Secondary objectives of the trial
    1. To assess the effect of brolucizumab compared with aflibercept with respect to anatomical outcomes
    2. To assess the effect of brolucizumab compared with aflibercept with respect to visual acuity
    3. To assess the effect of brolucizumab relative to aflibercept on the status of Diabetic Retinopathy
    4. To assess the safety and tolerability of brolucizumab compared to aflibercept
    5. To assess the immunogenicity of brolucizumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1- Signed informed consent must be obtained prior to participation in the study
    2- Patients to be 18 years of age or over at baseline
    3- Patients with type 1 or type 2 diabetes mellitus and HbA1c ≤ 12% at screening
    3- Patients with visual impairment due to DME with
    -BCVA score between 73 and 23 letters, inclusive, using ETDRS visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/40 to 20/320) at both screening and baseline.
    -DME involving the center of the macula, with CSFT ≥ 320 μm on SD-OCT at screening
    E.4Principal exclusion criteria
    Ocular conditions
    -High-risk proliferative diabetic retinopathy (PDR) in the study eye as per investigator assessment at both screening and baseline
    -Concomitant conditions or ocular disorders in the study eye at screening or baseline which may, in the opinion of the investigator, confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 12-month study period (eg, structural
    damage of the fovea, vitreous hemorrhage, retinal detachment, vitreomacular traction, macular hole, retinal vein/arterial occlusion,
    neovascularization of iris or choroidal neovascularization (CNV) of any cause).
    -Any active intraocular or periocular infection or active intraocular inflammation in the either eye at screening or baseline.
    -Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator’s judgment at
    screening or baseline
    -Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200 at screening (except when due to conditions whose surgery
    may improve VA, eg, cataract)
    Ocular treatments
    -Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to
    baseline
    -Use of intraocular or periocular corticosteroids including dexamethasone intravitreal implant (Ozurdex) in the study eye during the 6-month period
    prior to baseline, and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline
    -Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in BCVA at Week 52
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and Week 52
    E.5.2Secondary end point(s)
    1.
    -Change from baseline in CSFT at each post-baseline visit
    -Proportion of study eyes with fluid-free macula at each post-baseline visit
    -Proportion of study eyes with absence of DME (CSFT < 280 μm) at each post-baseline visit
    -Time to first fluid-free macula
    -Time to first absence of DME (CSFT < 280 μm)
    2.
    -Change from baseline in BCVA at each post-baseline visit
    -Proportion of study eyes with gain in BCVA of 5/10/15 letters or more at each post-baseline visit compared to baseline
    3.
    -Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (DRSS) score at Week 12, Week 24 and Week 52
    4.
    -Incidence of ocular and non-ocular Adverse Events (AEs)
    5.
    -Anti-drug antibody (ADA) measurement
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline, Weeks 12, 24, 52
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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) Yes
    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 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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
    Hungary
    Israel
    Slovakia
    United States
    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 years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    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: 371
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 124
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 495
    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)
    A patient will be considered to have completed the study when the patient has completed the last visit planned in the protocol.
    The investigator and/or referring physician will recommend the appropriate follow-up medical care, if needed, for all patients who are prematurely withdrawn from the study.
    After study completion the subject might receive standard of care if needed.
    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 Decision2019-07-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-03-24
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