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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fakultni Nemocnice Brno

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

29 Jun 2022 → ongoing

Decision date (initial)

2024-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AZV ČR – Agentura pro zdravotnický výzkum České republiky

External identifiers

EU CT number

2024-515888-54-00

EudraCT number

2020-002046-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Dose response, Safety

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.

Secondary objectives 8

1. Secondary objectives in relation to efficiency: Difference of AXL over 12M administration period with 0,04% atropine versus placebo, with 0,02% atropine versus 0,04% atropine
2. Difference in AXL over 24M administration period with 0,02% and 0,04% atropine versus placebo and mutually
3. Rebound phenomenon in both active arms (0,02% and 0,04%) in period 24M-36M versus placebo and mutually
4. Cycloplaegic spherical equivalent refraction (SER) difference for 12M administration period (0,02%, 0,04% versus placebo and mutually)
5. Cyloplaegic SER difference for 24M administration period (0,02% and 0,04% versus placebo and mutually)
6. Difference AXL/CR index for 12M administration period (0,02% and 0,04% versus placebo and mutually)
7. Difference AXL/CR index for 24M administration period (0,02% and 0,04% versus placebo and mutually)
8. Visual functional characteristics (BCDVA-best corrected distance visual acuity;BCNVA-best corrected near visual acuity;contrast sensitivity;colour perception)

Conditions and MedDRA coding

Myopia in children

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 at least on one of the 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): KI < 1,07, ISV < 37 at least on one of the eyes
5. Normal ocular finding and history in both eyes (except for spectacle correction and banal eye diseases, eg history of acute conjunctivitis, lacrimal lavage in early childhood)
6. Normal binocular functions in both eyes (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) in both eyes
8. Fulfillment of the indication criterion of AXL growth in 6-8M in 9M observation period before enrollment to the study according to the data in the patient medical documentation in at least on one of the eyes: Age AXL growth in 6M AXL growth in 7M AXL growth in 8M 6-7 years, 0.10 mm 0.11 mm 0.12 mm 8-9 years, 0.11 mm 0.12 mm 0.13 mm 10-11 years, 0.12 mm 0.13 mm 0.14 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 threeyear period of clinical examinations every six months and weekly keeping of diary entries during this period.

Exclusion criteria 10

1. Previous pharmacological, surgical and / or orthokeratological therapy of myopia
2. Previous long-term treatment with atropine
3. Presence and / or history of allergic reaction to ophthalmologics (atropine; cycloplegics - cyclopentolate, tropicamide; local anesthetics - eg oxybuprocaine, etc.)
4. Presence of strabism, amblyopia, glaucoma, corneal damage and / or corneal scarring and current and / or previous ocular conservative, contactology and / or surgical therapy
5. Presence and / or history of general disease (incl. allergy, myasthenia gravis, cardiac, respiratory and / or renal-urological disease and / or dysfunction)
6. Presence or scheduled launch of long-term (i.e. longer than 14 days) general and/or local drug therapy and/or scheduled surgical therapy for the participation in the study
7. Concomitant use of monoamine oxidase inhibitors (MAOIs)
8. Pregnancy, ev. breast feeding
9. General diseases, that can lead to myopia (Marfan's, Stickler's syndrome) or affect visual functions (diabetes mellitus, chromosomal anomalies)
10. Presence of rhinitis sicca

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 18

1. Difference of AXL over 12M administration period with 0,04% atropine versus placebo
2. Difference of AXL over 12M administration period with 0,02% atropine versus 0,04%
3. Difference in AXL over 24M administration period with 0,02% and 0,04% atropine versus placebo and mutually
4. Rebound phenomenon in both active arms (0,02% and 0,04%) in the period 24M - 36M against placebo and mutually
5. Cycloplaegic spherical equivalent refraction (SER) difference for 12M administration period (0,02% and 0,04% versus placebo and mutually)
6. Cyloplaegic SER difference for 24M administration period (0,02% and 0,04% versus placebo and mutually)
7. Difference AXL / CR index for 12M administration period (0,02% and 0,04% against placebo and mutually)
8. Difference of AXL / CR index for 24M administration period (0,02% and 0,04% against placebo and mutually)
9. Visual functional characteristics (BCDVA - best corrected distance visual acuity; BCNVA - best corrected near visual acuity; contrast sensitivity; colour perception)
10. Other growth characteristics of the eye (anterior segment biometry: corneal topography and keratometry, anterior chamber, lens thickness, horizontal anterior chamber dimension (WTW); choroidal thickness)
11. Functional characteristics of the eye (NPA - near-point of accommodation; NPC - near point of convergence; facility of accommodation))
12. SE peripheral defocus
13. Influence of genetic predisposition (parental refractive error, body height and BMI)
14. Influence of lifestyle (living outside, close work including technologies)
15. The intensity, severity and frequency of all side effects - Systemic (heart rate and other reported adverse events) - Ophthalmological TRAE - Subjects' visual comfort - Retinal vascular change,RNFL - retinal layers of nerve fibers, intraocular pressure, iris colour - Static photoreaction (photopic and [scotopic] mesopic pupil diameter) - NPA, NPC and facility of accommodation - Corneal and conjunctival irritation (Oxford fluorescein test)
16. Compliance stated by the patient (or parents, legal representative)
17. Quality of life and discomfort associated with therapy: self-assessment of younger patients
18. Impact of atropine therapy on quality of life (ATI Pediatric Eye Disease Investigator Group [PEDIG]) assessed by patient and parents / legal guardian

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fakultni Nemocnice Brno

Sponsor organisation

Fakultni Nemocnice Brno

Address

Cernopolni 9, Cerna Pole Cerna Pole

City

Brno-Sever

Postcode

613 00

Country

Czechia

Scientific contact point

Organisation

Fakultni Nemocnice Brno

Contact name

Rudolf Autrata

Public contact point

Organisation

Fakultni Nemocnice Brno

Contact name

Rudolf Autrata

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications