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    The EU Clinical Trials Register currently displays   44311   clinical trials with a EudraCT protocol, of which   7356   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:2014-003041-10
    Sponsor's Protocol Code Number:CRFB002H2301
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-01-20
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-003041-10
    A.3Full title of the trial
    RAINBOW study: a randomized, controlled study evaluating the efficacy and safety of RAnibizumab compared with laser therapy for the treatment of INfants BOrn prematurely With retinopathy of prematurity
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    This study is to find out if ranibizumab is safe and effective compared to laser therapy in preterm babies with ROP, a condition of abnormal blood vessel (arteries and veins) development in the eyes
    A.4.1Sponsor's protocol code numberCRFB002H2301
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/186/2014
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNOVARTIS FARMA S.p.A.
    B.1.3.4CountryItaly
    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 FARMA S.p.A.
    B.5.2Functional name of contact pointDrug Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressLargo Umberto Boccioni, 1
    B.5.3.2Town/ cityORIGGIO
    B.5.3.3Post code21040
    B.5.3.4CountryItaly
    B.5.4Telephone number+390296541
    B.5.5Fax number+39029659066
    B.5.6E-mailinfo.studiclinici@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 RFB002
    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 Yes
    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
    Retinopathy of prematurity (ROP)
    E.1.1.1Medical condition in easily understood language
    Retinopathy of prematurity (ROP) is a pathologic process that occurs in the developing retina of low birth-weight preterm neonates.
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10038933
    E.1.2Term Retinopathy of prematurity
    E.1.2System Organ Class 10015919 - Eye 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 demonstrate that intravitreal ranibizumab 0.2 mg has superior efficacy to laser therapy in the treatment of ROP as measured by the absence of active ROP and absence of unfavorable structural outcomes in both eyes 24 weeks after starting investigational treatment.
    E.2.2Secondary objectives of the trial
    To evaluate
    • whether IVT ranibizumab 0.2 mg has superior efficacy to IVT ranibizumab 0.1 mg in the treatment of ROP as measured by the absence of active ROP and absence of unfavorable structural outcomes in both eyes
    • whether IVT ranibizumab 0.1 mg has superior efficacy to laser therapy in the treatment of ROP as measured by the absence of active ROP and absence of unfavorable structural outcomes in both eyes 24 weeks after starting investigational treatment
    • the time to intervention with a 2nd modality for ROP or development of unfavorable structural outcome, or death
    • the recurrence of ROP and the requirement for additional intervention at 24 weeks
    • the ocular and systemic safety of IVT ranibizumab 0.1 mg / 0.2 mg
    • the systemic PK of IVT ranibizumab
    • the effects of investigational treatment on systemic VEGF levels in patients with ROP
    • To assess the number of ranibizumab administrations needed in the treatment of patients with ROP
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients have to fulfill all of the following criteria prior to receiving the first investigational treatment:
    1. Signed informed consent from parent(s) or legal guardian(s), in compliance with local requirements
    2. Male or female preterm infants with a birth weight of less than 1500 g
    3. Bilateral ROP with 1 of the following retinal findings in each eye:
    • Zone I, stage 1+, 2+, 3 or 3+ disease, or
    • Zone II, stage 3+ disease, or
    • Aggressive posterior ROP
    E.4Principal exclusion criteria
    Patients fulfilling any of the following criteria prior to receiving the first investigational treatment are not eligible for inclusion in this study.
    Investigational treatment is not clinically appropriate for the following patients:
    1. Have ROP disease characteristic in either eye, other than that listed in “Inclusion Criteria” above, at the time of the firstinvestigational treatment
    2. Are not suitable for treatment with either laser or intravitreal anti-VEGF therapy
    3. Have a history (either the patient or the mother) of hypersensitivity to any of the investigational treatments or to drugs of similar chemical classes
    Risk of confounding efficacy and/or safety assessments in the following patients:
    4. Have received any previous surgical or nonsurgical treatment for ROP (e.g., ablative laser therapy or cryotherapy, vitrectomy)
    5. Have been previously exposed to any intravitreal or systemic anti-VEGF agent (either the patient or the mother during this child’s pregnancy)
    6. Have used (either the patient or the mother) other investigational drugs as part of another clinical study (other than vitamins and minerals) within 30 days or within 5 half-lives of the other investigational drug, whichever is longer
    7. Have ocular structural abnormalities that are assessed by the Investigator to have a clinically significant impact on study assessments
    8. Have active ocular infection within 5 days before or on the day of first investigational treatment
    9. Have a history of hydrocephalus requiring treatment
    10. Have a history of any other neurological conditions that are assessed by the Investigator to have a significant risk of severe impact on visual function
    11. Have any other medical conditions or personal circumstances that are assessed by the Investigator to have a clinically relevant impact on study participation, any of the study procedures, or on efficacy assessments (e.g., poor life expectancy, clinically significant comorbidities, pupil not able to be adequately dilated,unable to comply with the visit schedule)
    E.5 End points
    E.5.1Primary end point(s)
    Absence of active ROP and absence of unfavorable structural outcomes in both eyes 24 weeks after starting investigational treatment
    E.5.1.1Timepoint(s) of evaluation of this end point
    24 weeks
    E.5.2Secondary end point(s)
    • The components that constitute the definition of absence of active ROP and unfavorable ocular outcomes at 24 weeks after starting investigational treatment
    • Any of the following unfavorable structural outcomes in either eye at 24 weeks after the first investigational treatment: retrolental membrane obscuring the view of the posterior pole, substantial temporal retinal vessel dragging causing abnormal structural features/ macular ectopia, posterior retinal fold involving the macula, retinal detachment involving the macula
    • The time after the first investigational treatment to the first occurrence of one of the following:
    - Death
    - Intervention for ROP with a treatment modality other than the modality of the first investigational treatment
    - An unfavorable structural outcome in either eye
    • Requirement of none, 1, or 2 ranibizumab re-treatments (whether unilateral or bilateral retreatment)
    • Recurrence of ROP requiring any intervention at 24 weeks
    E.5.2.1Timepoint(s) of evaluation of this end point
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    laser therapy
    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 EEA38
    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
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Bulgaria
    Canada
    Chile
    Colombia
    Croatia
    Czech Republic
    Denmark
    Egypt
    Estonia
    Finland
    France
    Germany
    Greece
    Hungary
    India
    Indonesia
    Israel
    Italy
    Japan
    Korea, Republic of
    Lithuania
    Malaysia
    Mexico
    Netherlands
    Norway
    Panama
    Peru
    Poland
    Portugal
    Romania
    Russian Federation
    Saudi Arabia
    Singapore
    Slovakia
    South Africa
    Spain
    Sweden
    Switzerland
    Taiwan
    Turkey
    Ukraine
    United Arab Emirates
    United Kingdom
    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 years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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: 300
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F.1.1.2.1Number of subjects for this age range: 300
    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) 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 No
    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
    The patient population consists of preterm born infants, therefore an inclusion criteria is the written informed consent from a parent or legal guardian
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 87
    F.4.2.2In the whole clinical trial 300
    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 eligible patients must be offered participation in a follow-up until they are five years of age to assess ocular effects (including those related to intravitreal administration), clinical and neurodevelopmental outcomes.
    This follow-up trial has the following study number: CRFB002H2301E1
    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 Decision2015-04-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-14
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