Kliniska prövningar Nct sida

Summary
EudraCT Number:2020-002046-16
Sponsor's Protocol Code Number:MARS_2020
National Competent Authority:Czechia - SUKL
Clinical Trial Type:EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:2020-05-18
Trial 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
A. Protocol Information
A.1Member State ConcernedCzechia - SUKL
A.2EudraCT number2020-002046-16
A.3Full title of the trial
A Randomised, double-blinded, placebo-controlled, multicenter study of efficacy, safety and side effects of highly diluted atropine collyrium in slowing the progression of myopia (shortsightedness) in children
Randomizovaná dvojitě zaslepená placebem kontrolovaná multicentrická studie účinnosti a bezpečnosti vysoce ředěného atropinového collyria při zpomalování rozvoje krátkozrakosti u dětí
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Efficacy, safety and side effects of diluted atropin eye drops in slowing the progression of shortsightedness (myopia) in children.
Účinnost, bezpečnost a vedlejší účinky ředěných atropinových očních kapek na zpomalování rozvoje krátkozrakosti (myopie) u dětí.
A.3.2Name or abbreviated title of the trial where available
M.A.R.S.
M.A.R.S.
A.4.1Sponsor's protocol code numberMARS_2020
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 SponsorFakultní nemocnice Brno
B.1.3.4CountryCzech Republic
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAZV ČR
B.4.2CountryCzech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationMasarykova univerzita - Lékařská fakulta
B.5.2Functional name of contact pointCentrum pro klinická hodnocení
B.5.3 Address:
B.5.3.1Street AddressKamenice 5
B.5.3.2Town/ cityBrno
B.5.3.3Post code625 00
B.5.3.4CountryCzech Republic
B.5.4Telephone number00420549496526
B.5.6E-maildemlova@med.muni.cz
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.3.1Product nameAtropini collyrium 0.02%
D.3.4Pharmaceutical form Eye drops
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOcular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNATROPINE SULFATE
D.3.9.1CAS number 55-48-1
D.3.9.4EV Substance CodeSUB00625MIG
D.3.10 Strength
D.3.10.1Concentration unit % (W/W) percent weight/weight
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.02
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
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.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 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.3.1Product nameAtropini collyrium 0.04%
D.3.4Pharmaceutical form Eye drops
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOcular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNATROPINE SULFATE
D.3.9.1CAS number 55-48-1
D.3.9.4EV Substance CodeSUB00625MIG
D.3.10 Strength
D.3.10.1Concentration unit % (W/W) percent weight/weight
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.04
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
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 placeboEye drops
D.8.4Route of administration of the placeboOcular use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Myopia in children
Krátkozrakost u dětí
E.1.1.1Medical condition in easily understood language
Myopia in children
Krátkozrakost u dětí
E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
MedDRA Classification
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 the clinical trial is to determine the difference in axial eye length (AXL) over a 12M application period with 0.02% atropine versus placebo.
Primárním cílem klinického hodnocení je zjištění diference axiální délky oka (AXL) za 12M aplikační periody při aplikaci 0,02% atropinu proti placebu.
E.2.2Secondary objectives of the trial
• Difference of AXL over the 12M administration period with 0.04% atropine versus placebo
• Difference of AXL over a 12M administration period at 0.02% atropine versus 0.04%
• Difference in AXL over 24M administration period with 0.02% and 0.04% atropine versus placebo and
• Rebound phenomenon in both active branches (0.02% and 0.04%) in the period 24M − 36M against placebo and each other
• Spherical equivalent refraction difference (SER) for 12M administration period (0.02% and 0.04% versus placebo and each other)
• SER difference for 24M administration period (0.02% and 0.04% versus placebo and each other)
• Difference AXL / CR index for 12M administration period (0.02% and 0.04% against placebo and each other)
• Difference of AXL / CR index for 24M administration period (0.02% and 0.04% against placebo and each other)
• Visual functional characteristics (BCDVA - best corrected distance visual acuity; BCNVA - best corrected near visual acuity; contrast sensitivity)
• Diference AXL za 12M aplikační periody při aplikaci 0,04% atropinu proti placebu
• Diference AXL za 12M aplikační periody při aplikaci 0,02% atropinu proti koncentraci 0,04%
• Diference AXL za 24M aplikační periody při aplikaci 0,02% a 0,04% atropinu proti placebu i navzájem
• Rebound fenomén v obou aktivních větvích (0,02% a 0,04%) v období 24M−36M proti placebu i navzájem
• Diference sférického ekvivalentu refrakce (SER) za 12M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference SER za 24M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference indexu AXL/CR za 12M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference indexu AXL/CR za 24M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Zrakové funkční charakteristiky (BCDVA – best corrected distance visual acuity; BCNVA – best corrected near visual acuity; kontrastní citlivost)
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1) Age 6-12 years
2) Diagnosis of myopia - spherical component of refraction -0.5 Dsf to -4.75 Dsf and astigmatism 0 to -2.5 Dcyl in both eyes
3) BCDVA of worse eye better or equal to 0.2 logMAR (according to ETDRS test, 85 cd / m2)
4) Corneal topography index (anterior corneal area): ISV <37
5) Normal ocular finding and history (except for spectacle correction and banal eye diseases, eg history of acute conjunctivitis, lacrimal lavage in early childhood)
6) Normal binocular functions (in sensory and motor components) with the exception of exophoria equal to or more than 8 Dp incl. in an alternating covering test with prisms
7) Normal intraocular pressure (≤ 22 torr, contactless applanation)
8) Fulfillment of the indication criterion of AXL growth at 6M in the pre-randomization period of the study:
Age band AXL growth in 6M
6-7 years 0.10 mm
8-9 years 0.11 mm
10-11 years 0.12 mm
9) The willingness of the patient and his / her parents / legal guardian to undergo a two-year period of daily application of eye drops, a three-year period of clinical examinations every six months and weekly keeping of diary entries during this period.
1) Věk 6−12 let (do 12. narozenin v den randomizace včetně)
2) Diagnóza myopie – sférická složka refrakce -0,5 Dsf až -4,75 Dsf a astigmatismus 0 až -2,5 Dcyl na obou očích
3) BCDVA horšího oka lepší nebo rovno 0,2 logMAR (dle ETDRS testu, 85 cd/m2)
4) Index rohovkové topografie (přední plocha rohovky): ISV < 37
5) Normální oční nález a anamnéza (s výjimkou brýlové korekce a banálních očních onemocnění, např. akutní konjunktivitida v anamnéze, průplach slzných cest v raném dětství)
6) Normální binokulární funkce (v senzorické a motorické složce) s výjimkou exoforie rovné nebo více než 8 Dp vč. v alternujícím zakrývacím testu s prizmaty
7) Normální nitrooční tlak (≤ 22 torr, bezkontaktní aplanací)
8) Splnění indikačního kritéria růst AXL za 6M v předrandomizační periodě studie:
Věkové pásmo - růst AXL za 6M
6−7 let 0,10 mm
8−9 let 0,11 mm
10−11 let 0,12 mm
9) Ochota pacienta i jeho rodičů/zákonného zástupce podstoupit dvouletou periodu každodenní aplikace očních kapek, tříletou periodu klinických vyšetření každého půl roku a týdenní vedení deníkových záznamů v tomto období.
E.4Principal exclusion criteria
1) General diseases with myopia (Marfan's, Stickler's syndrome) or affecting visual functions (diabetes mellitus, chromosomal anomalies)
2) Previous pharmacological, surgical and / or orthokeratological therapy of myopia
3) Previous long-term treatment with atropine
4) Presence and / or history of allergic reaction to ophthalmologics (atropine; cycloplegics - cyclopentolate, tropicamide; local anesthetics - eg oxybuprocaine, etc.)
5) Presence of strabism, amblyopia, glaucoma, corneal damage and / or scarring and current and / or previous ocular conservative, contactology and / or surgical therapy
6) Presence and / or history of general disease (incl. Allergy, myasthenia gravis, cardiac, respiratory and / or renal-urological disease and / or dysfunction)
7) Presence and / or history of long-term general and / or local drug and / or surgical therapy
8) Concomitant use of monoamine oxidase inhibitors (MAOIs)
9) Pregnancy, ev. breast feeding
1) Celková onemocnění disponující k myopii (Marfanův, Sticklerův syndrom) nebo ovlivňující vizuální funkce (diabetes mellitus, chromosomové anomálie)
2) Předchozí farmakologická, chirurgická a/nebo ortokeratologická terapie myopie
3) Předchozí dlouhodobá léčba atropinem
4) Přítomnost a/nebo anamnéza alergické reakce na oftalmologika (atropin; cykloplegika – cyklopentolát, tropikamid; lokální anestetika – např. oxybuprokain atd.)
5) Přítomnost strabismu, amblyopie, glaukomu, poškození a/nebo jizvení rohovky a stávající a/nebo dřívější oční konzervativní, kontaktologická a/nebo chirurgická terapie
6) Přítomnost a/nebo anamnéza celkového onemocnění (vč. alergie, myastenie gravis, kardiálního, respiračního a/nebo renálně-urologického onemocnění a/nebo dysfunkce)
7) Přítomnost a/nebo anamnéza dlouhodobé celkové a/nebo lokální medikamentózní a/nebo chirurgické terapie
8) Souběžné užívání inhibitorů monoaminooxidázy (IMAO)
9) Těhotenství, ev. kojení
E.5 End points
E.5.1Primary end point(s)
The primary objective of the clinical trial is to determine the difference in axial eye length (AXL) over a 12M application period with 0.02% atropine versus placebo.
Primárním cílem klinického hodnocení je zjištění diference axiální délky oka (AXL) za 12M aplikační periody při aplikaci 0,02% atropinu proti placebu.
E.5.1.1Timepoint(s) of evaluation of this end point
12 M
12 měsíců
E.5.2Secondary end point(s)
• Difference of AXL over the 12M administration period with 0.04% atropine versus placebo
• Difference of AXL over a 12M administration period at 0.02% atropine versus 0.04%
• Difference in AXL over 24M administration period with 0.02% and 0.04% atropine versus placebo and
• Rebound phenomenon in both active branches (0.02% and 0.04%) in the period 24M − 36M against placebo and each other
• Spherical equivalent refraction difference (SER) for 12M administration period (0.02% and 0.04% versus placebo and each other)
• SER difference for 24M administration period (0.02% and 0.04% versus placebo and each other)
• Difference AXL / CR index for 12M administration period (0.02% and 0.04% against placebo and each other)
• Difference of AXL / CR index for 24M administration period (0.02% and 0.04% against placebo and each other)
• Visual functional characteristics (BCDVA - best corrected distance visual acuity; BCNVA - best corrected near visual acuity; contrast sensitivity)
• Diference AXL za 12M aplikační periody při aplikaci 0,04% atropinu proti placebu
• Diference AXL za 12M aplikační periody při aplikaci 0,02% atropinu proti koncentraci 0,04%
• Diference AXL za 24M aplikační periody při aplikaci 0,02% a 0,04% atropinu proti placebu i navzájem
• Rebound fenomén v obou aktivních větvích (0,02% a 0,04%) v období 24M−36M proti placebu i navzájem
• Diference sférického ekvivalentu refrakce (SER) za 12M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference SER za 24M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference indexu AXL/CR za 12M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Diference indexu AXL/CR za 24M aplikační periody (0,02% a 0,04% proti placebu i navzájem)
• Zrakové funkční charakteristiky (BCDVA – best corrected distance visual acuity; BCNVA – best corrected near visual acuity; kontrastní citlivost)
E.5.2.1Timepoint(s) of evaluation of this end point
12 M, 24 M, 36 M
12 měsíců, 24 měsíců, 36 měsíců
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 Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
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 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 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 concerned5
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
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
Last patient, last visit
Poslední pacient, poslední návštěva
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 months6
E.8.9.1In the Member State concerned 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: 344
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) Yes
F.1.1.5.1Number of subjects for this age range: 300
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 44
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 No
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 No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state344
F.4.2 For a multinational trial
F.4.2.2In the whole clinical trial 344
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
Žádné
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 Decision2020-06-23
N.Ethics Committee Opinion of the trial application
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion
P. End of Trial
P.End of Trial Status

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