A randomized, double-blind, placebo-controlled dose-finding study of 0.05%, 0.025%, 0.01% and 0.005% atropine eye drops to inhibit myopia progression in children in a European population

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharma Stulln GmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

19 Sep 2022 → 15 Apr 2025

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516758-23-00

EudraCT number

2021-004884-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Therapy

To evaluate the optimal dose of low-dose atropine eye drops compared to placebo for the inhibition of myopia progression in children

Secondary objectives 1

1. To evaluate anatomical and functional effects of low-dose atropine eye drops compared to placebo

Conditions and MedDRA coding

Myopia progression in children

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male subjects and female subjects from 6 to 12 years of age. (female subjects who cannot become pregnant and female subjects of child bearing potential (after menarche) who use an highly effective contraceptive method or strategy (failure rate per year < 1%) according to the CTFG Guidance "Recommendations related to contraception and pregnancy testing in clinical trials, version 1.1, updated"; see Section 11.3).
2. Subjects showing myopia between ≥-1.0 and ≤-4.0 D (spherical equivalent as assessed by autorefraction under cycloplegia) and a progression of myopia within the past 12 months in at least one eye.
3. Parents or legal guardians who have been informed about the clinical study and have signed the informed consent form.

Exclusion criteria 23

1. Anisometropia (SE) > |1.0| D
2. Concomitant Therapy within the last 3 Months prior to Enrollment: 10. Treatment with sympathomimetics
3. Concomitant Therapy within the last 3 Months prior to Enrollment: 11. Treatment with drugs that may increase the anticholinergic effect of atropine: - Amantadine - Anti-arrhymics such as chinidine, procainamide and disopyramide - Dopamine-antagonists such as metoclopramide - Antihistaminics - Certain anti-Parkinsonian drugs (except dopamine receptor agonists) - Neuroleptics
4. Concomitant Therapy within the last 3 Months prior to Enrollment: 12. Treatment with pilocarpin and physostigmine containing drugs
5. Concomitant Therapy within the last 3 Months prior to Enrollment:13. Treatment with digoxine and nitrofurantoin
6. Concomitant Therapy within the last 3 Months prior to Enrollment: 14. Treatment with phenothiazine
7. Concomitant Therapy within the last 3 Months prior to Enrollment: 15. Treatment with levodopa
8. Enrolment in another clinical study within the last 4 weeks or during enrolment in this study
9. East Asian or African origin
10. Previous or current alcohol or drug abuse
11. Mental or emotional instability of the subject, parents or legal guardians that might jeopardize the validity of the informed consent or the compliance with the study procedures.
12. Corneal astigmatism (ΔTK) > |1.5| D
13. Unreliability or lack of cooperation
14. History of any myopia treatment within 3 months before inclusion: e.g. DIMS glasses, Orthokeratology contact lenses, multifocal contact lenses, atropine eye drops
15. Pregnancy
16. Best corrected visual acuity VADecimal< 1.0 (VAlogMAR > 0.0)
17. Pathological findings in the eyes, i.e. pathological myopia, corneal scars and pathologies in the anterior or posterior segments of the eye
18. Known intolerances to atropine eye drops or known hypersensitivity to any of the other components of the investigational product, allergies against eye drops
19. Presence of a contraindication for the treatment with atropine: - Hypersensitivity to the active substance or to any of the excipients. - Primary forms of glaucoma - narrow-angle glaucoma - rhinitis sicca - Narrow-angel of anterior chamber - Tachycardia, congestive heart failure, coronary stenoses - Thyrotoxicosis, hyperthyroidism - Mechanical obstruction of the gastrointestinal tract - Paralytic ileus - Megacolon - Obstructive urinary tract diseases, e.g. prostatic hypertrophy with residual urine formation - Myasthenia gravis - Acute pulmonary edema - Pregnancy toxicosis - Spastic paralysis
20. Down syndrome
21. Concomitant Therapy within the last 3 Months prior to Enrollment: 8. Any ocular therapy other than the IMP, except for antibiotic or antiallergic eye drops
22. Concomitant Therapy within the last 3 Months prior to Enrollment: 9. Treatments with - Monoamine oxidase (MAO) inhibitor therapy - Antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserine)
23. Other reasons why, in the opinion of the investigator, the subjects should not participate in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the change of myopia determined by the spherical equivalent measured by autorefractor measurement with cycloplegia in the following 12 months after the beginning of low dose atropine treatment.

Secondary endpoints 2

1. The secondary efficacy endpoints are the changes in - Axial eye growth - Anterior chamber depth - IOL-power for Spheris 209 - Lens thickness - Pupil size under photopic and scotopic conditions - Accommodation - Best corrected visual acuity and distance corrected near visual acuity - Atropine effects as a function of iris pigmentation in the course of 12 months of low dose Atropine treatment.
2. Safety: Change from Baseline to Day 365 in: - IOP - Appearance of the macula Incidence of - Local adverse drug reactions - Systemic adverse drug reactions as assessed by the subject/caregiver. Incidence of adverse events assessed by investigator

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharma Stulln GmbH

Sponsor organisation

Pharma Stulln GmbH

Address

Werksstrasse 3

City

Stulln

Postcode

92551

Country

Germany

Scientific contact point

Organisation

Pharma Stulln GmbH

Contact name

Pharma Stulln

Public contact point

Organisation

Pharma Stulln GmbH

Contact name

Pharma Stulln

Third parties 1

Sponsor responsibilities

Contact point sponsor

Pharma Stulln GmbH

Locations

1 EU/EEA country · 4 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

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

Application history

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