A phase III, randomized, double-masked, placebo-controlled, parallel-group, multicenter study of the safety and efficacy of OT-101 (Atropine Sulfate 0.01%) in treating the progression of myopia in pediatric subjects

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ocumension (Hong Kong) Ltd.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

27 May 2022 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ocumension (Hong Kong) Limited

External identifiers

EU CT number

2024-516315-24-00

EudraCT number

2020-003976-42

ClinicalTrials.gov

NCT04770610

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the efficacy of OT- 101 Ophthalmic Solution in treating the progression of myopia in Pediatric subjects following 3 years treatment

Secondary objectives 1

1. To evaluate the safety and tolerability of OT-101 Ophthalmic Solution in Pediatric subjects with myopia

Conditions and MedDRA coding

myopia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. A parent or legal guardian of each subject must provide written informed consent and sign the Health Insurance Portability and Accountability Act (HIPAA) form (or equivalent, if applicable), approved by the appropriate Institutional Review Board (IRB)/Ethical Committee (EC). Whenever practical and appropriate per local requirements, a child’s assent should also be sought before inclusion into the study. UK, Hungary, Poland, I reland, Slovakia, Spain: The protocol is being conducted in various countries with varying ages for consent and is written to require informed consent procedures for minors in Europe based on national requirements, based on the latest guidelines on informed consent of minors. For subjects reaching age of consent during the study duration as per local requirements, consent must be obtained on the appropriate Participant Consent Form
2. Be able to comply with study requirements, attend all study visits, have ability to read and understand native language of subject, and be accompanied by a parent/legal guardian
3. Be between 3-15 years of age of either sex and any race or ethnicity at Visit 1 (Day -14 to -1)
4. Have refractive error by cycloplegic autorefraction at baseline (Visit 1) in the study eye of: a. myopia between -1.00 D and -6.00 D, inclusive, of spherical equivalent b. astigmatism less than or equal to 1.50 DC
5. Have anisometropia ≤ 1.0 D of spherical equivalent at Visit 1
6. Have a best-corrected distance visual acuity of (BCVA) of logarithm of the minimum angle of resolution (logMAR) ≤ 0.4 (approximately Snellen 20/50) for 3 year olds; logMAR ≤ 0.3 (approximately Snellen 20/40) for 4 year olds; logMAR ≤ 0.18 (approximately Snellen 20/30) for ≥ 5 year olds) in each eye as measured using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart [R,1 or 2], or Lea Chart for subjects who do not know the alphabet, at Visit 1 and Visit 2
7. Ireland, Slovakia, Spain, US, China: Females of childbearing potential agree to have urine pregnancy testing performed at screening (must be negative); must not be lactating; and must agree to use a medically acceptable form of birth control throughout the study duration (i.e., Spermicide with barrier, oral contraceptive, injectable or implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner). For non-sexually active females, abstinence will be considered an acceptable form of birth control. Females of childbearing potential include all females who have experienced menarche and have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
8. Be able and willing to avoid all prohibited medications during the washout period between screening and randomization and during the study without significant risk to the subject.

Exclusion criteria 18

1. Have known contraindications or sensitivity to atropine, the study medications, or their components
2. Have clinically significant abnormal findings on slit lamp biomicroscopy exam (e.g., cataract) which may impact best corrected visual acuity measures in either eye at screening or a known history of a clinically significant slit lamps findings in either eye
3. Have clinically significant abnormal findings on indirect dilated fundoscopy exam in either eye at screening or a known history of a clinically significant retinal findings in either eye
4. Have any evidence of an eye movement disorder or restriction of extraocular movement (e.g., nystagmus)
5. Have an active ocular infection (i.e., bacterial, viral, or fungal)
6. Have active or a history of chronic or recurrent episodes of ocular inflammation (e.g., moderate to severe blepharitis, allergic conjunctivitis, peripheral ulcerative keratitis, scleritis) in either eye
7. Have a history of ocular herpetic infection, iritis, scleritis, or uveitis, whether active or inactive at screening
8. Have undergone any myopia control treatment including atropine, orthokeratology, rigid gas-permeable contact lenses, bifocal contact lenses, progressive addition spectacle lenses, or other lenses to reduce myopia progression in the previous 6 months. Myopic correction in the form of single-vision eyeglasses and/or single-vision soft contact lenses are allowed
9. Have undergone any form of refractive eye surgery including incisional keratotomy, photorefractive keratectomy [PRK], laser in situ keratomileusis [LASIK], laser-assisted sub-epithelial keratectomy [LASEK]), corneal inlay procedures, conductive keratoplasty, small incision lenticule extraction (SMILE), cataract extraction, or any form of intraocular lens implantation
10. Have intraocular pressure (IOP) that is < 9 millimeters of mercury (mmHg) or > 21 mmHg in either eye, or have a prior diagnosis of ocular hypertension or glaucoma or currently being treated with any type of topical IOP lowering (glaucoma) medication
11. Have had surgical intervention (ocular or systemic) within 6 months prior to Visit 1, or planned surgical intervention during the study
12. Use any of the following disallowed medications or therapies by any route of administration during the 2 weeks (14 days) prior to Visit 2 (Day 1): a. any prescription or over the counter ophthalmic products (Use of preservative-free artificial tears is allowed but may not be used within 2 hours of administration of study medication. Use of lubricating ointment form of artificial tears before bedtime is allowed but must be used at least 15 minutes after administration of study medication) b. monoamine oxidase inhibitors c. atropine, pirenzepine, or other anti-muscarinic agent d. any medication affecting the pupil or accommodation e. orthoK, rigid gas-permeable, bifocal, progressive-addition, multi-focal, or other lenses to reduce myopia progression In addition, Groups b–e above are not allowed for the duration of the study.
13. The anticipated need to use chronic ophthalmic or systemic oral corticosteroids during the study. Intranasal, inhaled, topical dermatologic, intra-articular, perianal steroids, and short-term oral steroids (< 2 weeks) are permitted
14. Participation in any other study of investigational therapy during the study period or within 30 Days before Visit 1
15. Female subjects who are pregnant, nursing, or plan to become pregnant at any time during the study
16. History or current evidence of a medical condition predisposing the patient to degenerative myopia (e.g., Marfan syndrome, Stickler syndrome) or a condition that may affect visual function or development (e.g., diabetes mellitus, chromosome anomaly)
17. Have a central nervous system disorder (e.g., epilepsy, cerebral disorders, Down syndrome)
18. Have a condition or a situation, which in the Investigator’s opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject’s study participation, including but not limited to unstable: cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of study eyes with a -0.75 D of progressive myopia at Month 36 defined as an increase in spherical equivalent of -0.75 D or greater (i.e., change from baseline ≥ -0.75) as assessed by cycloplegic autorefraction.

Secondary endpoints 2

1. Change from baseline to Month 36 in study eye spherical equivalent (D) as assessed by cycloplegic autorefraction
2. Change from baseline to Month 36 in study eye axial length as measured by cycloplegic biometry (a device will be selected and the same device to be used throughout the duration of this study)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ocumension (Hong Kong) Ltd.

Sponsor organisation

Ocumension (Hong Kong) Ltd.

Address

Rm 417 4/f, Lippo Ctr Twr Two Tower 2, 89 Queensway Lippo Ctr Twr Two Tower 2 89 Queensway

City

Admiralty

Country

Hong Kong

Scientific contact point

Organisation

Ocumension (Hong Kong) Ltd.

Contact name

Yang Shen

Public contact point

Organisation

Ocumension (Hong Kong) Ltd.

Contact name

Yang Shen

Third parties 2

Locations

5 EU/EEA countries · 16 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 49 files

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

Application history

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