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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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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    Summary
    EudraCT Number:2013-002626-23
    Sponsor's Protocol Code Number:CRFB002A2411
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-02-13
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2013-002626-23
    A.3Full title of the trial
    A 12-month, phase IIIb, randomized, visual acuity, assessor-masked, multicenter study assessing the efficacy and safety of ranibizumab 0.5mg in treat and extend regimen compared to monthly regimen, in patients with neovascular age-related macular degeneration
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and safety of two different treatment patterns of ranibizumab in patients with wet AMD
    A.3.2Name or abbreviated title of the trial where available
    TREND
    A.4.1Sponsor's protocol code numberCRFB002A2411
    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 Services 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 Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Healthcare A/S
    B.5.2Functional name of contact pointMedicinsk Information
    B.5.3 Address:
    B.5.3.1Street AddressEdvard Thomsens Vej 14
    B.5.3.2Town/ cityKøbenhavn S
    B.5.3.3Post code2300
    B.5.3.4CountryDenmark
    B.5.4Telephone number+4539168400
    B.5.5Fax number+4539168401
    B.5.6E-mailskriv.til@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 Lucentis
    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.3.1Product nameLucentis
    D.3.2Product code RFB002A
    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 INNRANIBIZUMAB
    D.3.9.1CAS number 347396-82-1
    D.3.9.2Current sponsor codeRFB002
    D.3.9.4EV Substance CodeSUB22314
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 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 Lucentis
    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.3.1Product nameLucentis
    D.3.2Product code RFB002
    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 IMPIntravitreal use
    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
    Visual impairment due to neovascular AMD
    E.1.1.1Medical condition in easily understood language
    Impaired vision due to growth of new vessels (neovascularization) in the choroid which is caused by an intrinsic substance, so-called vascular endothelial growth factor (VEGF)
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10060837
    E.1.2Term Choroidal neovascularization
    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
    The primary objective is to demonstrate that the ranibizumab Treat and Extend regimen is non-inferior to ranibizumab monthly regimen in patients with nAMD as assessed by the change in best corrected visual acuity (BCVA) from baseline to Month 12 .
    For the primary analysis a non-inferiority margin of five letters will be applied..
    E.2.2Secondary objectives of the trial
    To Evaluate
    • the number of visits scheduled according to the TER after treatment initiation.
    • the average change in BCVA from baseline to Month1 through Month 12, the time course of mean BCVA from baseline up to Month 12
    • the change in BCVA, the occurrence of BCVA losses of <5, <10 and <15 letters and the occurrence of absolute BCVA ≥73 letters (20/40 Snellen equivalent), the occurrence of BCVA improvements of ≥1, ≥5, ≥10, ≥15, and ≥30 letters, the occurrence of a fluid free macula from baseline, over time up to Month 12.
    • presence of active CNV leakage on fluorescein angiography (FA) over time up to Month 12
    • Assess treatment frequency and average dosing interval and the impact on patient functioning and quality of life supported by ranibizumab 0.5 as assessed by the NEI-VFQ-25
    • safety of 0.5 mg ranibizumab over 12 months
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent must be obtained before any study related procedure is performed.

    2. Male or female patients, ≥50 years of age.

    Inclusion criteria for the study eye at Screening:
    3. Visual impairment predominantly due to nAMD.

    4. Active CNV secondary to AMD confirmed by presence of active leakage from CNV seen by fluorescein angiography (FA) and/or color fundus photography

    5. Presence of intra- or subretinal fluid/hemorrhage seen by SD-OCT

    6. CNV or sequelae of the CNV (i.e., pigment epithelium detachment, subretinal or sub- RPE hemorrhage, blocked fluorescence, macular edema, or subretinal, sub-RPE or intraretinal fluid involving the center of the fovea

    7. The total area of fibrosis comprising less than 50% of the lesion area.

    8. BCVA score must be ≤ 78 and ≥ 23 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximate Snellen equivalent of 20/32 and 20/320)
    E.4Principal exclusion criteria
    Exclusion criteria for systemic medical history and conditions at Screening:
    1. Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
    2. Stroke or myocardial infarction within 3 months prior to Screening.
    3. Presence of uncontrolled systolic blood pressure > 160 mmHg or diastolic blood pressure > 100
    mmHg.
    4. Known hypersensitivity to the investigational drug (ranibizumab or any component of the Ranibizumab formulation) or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation.

    Exclusion criteria for ocular medical history and conditions at Screening:
    5. Any active periocular or ocular infection or inflammation in both eyes.
    6. Uncontrolled glaucoma (intraocular pressure [IOP] ≥30 mm Hg on medication or according to investigator’s judgment) in the study eye.
    7. Atrophy or fibrosis involving the center of the fovea in the study eye.
    8. History of focal/grid laser photocoagulation with involvement of the macular area at any time in the study eye.
    9. Ocular disorders in the study eye (i.e. retinal detachment, pre-retinal membrane of the macula or cataract with significant impact on visual acuity) at the time of enrollment that may confound interpretation of study results and compromise visual acuity.
    10. Presence of amblyopia or ocular disorders with final best corrected vision <20/200 or amaurosis in the fellow eye.

    Exclusion criteria for prior or current ocular treatment at Screening:
    11. History of treatment with any anti-angiogenic drugs (including any anti-VEGF agents) e.g., bevacizumab [Avastin®], aflibercept [Eylea®]) or vPDT in the study eye.
    12. History of intravitreal treatment with corticosteroids within 6 months prior to Screening in the study eye.
    13. History of intra-ocular surgery within 3 months in the study eye prior to the Screening. Exclusion criteria for prior or current systemic medication at Screening:
    14. Use of other investigational drugs (excluding vitamins, minerals) within 30 days or 5 half-lives from Screening, whichever is longer.
    15. Use of any systemic anti-VEGF drugs within 3 months prior to Screening (e.g., bevacizumab [Avastin®], ziv-aflibercept [Zaltrap®]).
    16. Current or planned use of systemic medications know to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil®), tamoxifen, henothiazines and ethambutol.

    Exclusion criteria for patient at Screening:
    17. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test.
    18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods include:
    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
    • Male sterilization (at least 6 m prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
    • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
    • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal
    contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or
    transdermal hormone contraception
    • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
    E.5 End points
    E.5.1Primary end point(s)
    Change in Best Corrected Visual Acuity (BCVA)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to month 12
    E.5.2Secondary end point(s)
    1) BCVA change over time; by measuring BCVA score at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts
    2) Number of visits scheduled
    3) avarage change in BCVA; BCVA score measured at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts
    4) Period (time) between injections
    5) Presence of the disease activity measured on the images by Reading center.
    6) Change in retinal thickness measured on OCT image by Reading center
    7) CNV leakage presence measured on Fluorescein angiography image by Reading center.
    8) Quality of Life
    E.5.2.1Timepoint(s) of evaluation of this end point
    From Month 1 through Month 12 (applicable to 1)
    From Month 1 to Month 11 (Applicable to 2)
    From Baseline to Month 12 (applicable to 3, 4, 5, 6, 7, 8)
    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 Yes
    E.6.13.1Other scope of the trial description
    Treatment monitoring
    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 Information not present in EudraCT
    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 Yes
    E.8.1.7.1Other trial design description
    Assessor masked to treatment regimen
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Monthly Lucentis regimen vs Treat and Extend Lucentis regimen
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA71
    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
    Chile
    Croatia
    Denmark
    Egypt
    Germany
    Hungary
    India
    Italy
    Korea, Republic of
    Portugal
    Russian Federation
    Serbia
    Slovakia
    Slovenia
    Spain
    Switzerland
    Turkey
    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 years1
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    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: 258
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 386
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Legal representative (legally authorised to act as personal representative to sign for patient) may sign ICF
    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 483
    F.4.2.2In the whole clinical trial 644
    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 - Lucentis is available on the market
    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 Decision2014-02-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-01-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-11-19
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