Phase III Randomized Double-Masked Placebo-Controlled Study of Atropine Sulfate 0.01% in Pediatric Myopia Progression
- Trial ID
- 2024-516315-24-00
- Protocol
- OT-101-001
- Sponsor
- Ocumension (Hong Kong) Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase III, randomized, double-masked, placebo-controlled, parallel-group, multicenter study is to evaluate the **efficacy** of OT-101 Ophthalmic Solution, containing Atropine Sulfate 0.01%, in treating the progression of **myopia** in pediatric subjects over a treatment period of three years. This is clinically relevant as myopia is a common refractive error in children that can lead to significant visual impairment and increased risk of ocular complications if not effectively managed.
Secondary objectives include:
- Evaluating the **safety** and tolerability of OT-101 Ophthalmic Solution in pediatric subjects with myopia. This assessment is crucial to ensure that the treatment is not only effective but also safe for long-term use in a pediatric population.
Participants
The clinical trial involves a total of **468 participants** diagnosed with **myopia**, aiming to evaluate the efficacy of OT-101 Ophthalmic Solution in treating the progression of this condition over a three-year period. The study population consists of pediatric subjects aged between 3 to 15 years, inclusive of both male and female participants, and representing any race or ethnicity. Participants were selected based on specific criteria, including a refractive error by cycloplegic autorefraction at baseline, with myopia ranging from -1.00 D to -6.00 D of spherical equivalent, and astigmatism less than or equal to 1.50 DC. The trial includes subjects with a best-corrected distance visual acuity of logMAR ≤ 0.4 for 3-year-olds, logMAR ≤ 0.3 for 4-year-olds, and logMAR ≤ 0.18 for those aged 5 years and older. The study requires participants to comply with all study requirements, attend all visits, and be accompanied by a parent or legal guardian. Additionally, females of childbearing potential must agree to undergo urine pregnancy testing and use a medically acceptable form of birth control throughout the study. The trial population is considered vulnerable, and informed consent procedures are adapted to meet the national requirements for minors in Europe. Participants are expected to avoid all prohibited medications during the washout period and throughout the study duration.
Plans and Procedures
The clinical trial is a **phase III**, randomized, double-masked, placebo-controlled, parallel-group, multicenter study designed to evaluate the safety and efficacy of OT-101 (Atropine Sulfate 0.01% Ophthalmic Solution) in treating the progression of **myopia** in pediatric subjects. The trial will span approximately three years, with an estimated end date of October 31, 2027. Participants will be randomly assigned to receive either the investigational drug or a placebo, which is composed of excipients used to manufacture the investigational drug but without the active drug substance. The study is structured to ensure that neither the participants nor the investigators know which treatment is being administered, maintaining the double-masked nature of the trial.
The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed. Participants must be between 3-15 years of age, have a refractive error by cycloplegic autorefraction within specified limits, and meet other inclusion criteria. Following the screening, participants will undergo randomization and commence treatment. Follow-up visits will occur at regular intervals to monitor safety and efficacy, with primary and secondary endpoints assessed at Month 36. The primary endpoint is the percentage of study eyes with a -0.75 D of progressive myopia at Month 36, while secondary endpoints include changes in spherical equivalent and axial length from baseline to Month 36.
The expected length of participant involvement is the full duration of the trial, approximately three years. However, conditions that may lead to early termination from the study include non-compliance with study requirements, adverse events, or withdrawal of consent. Participants are required to avoid prohibited medications during the washout period and throughout the study. The trial is conducted in compliance with ethical standards, requiring informed consent from a parent or legal guardian, and assent from the child when appropriate. The study aims to provide valuable data on the efficacy of atropine sulfate in slowing the progression of myopia in children, contributing to the understanding and management of this common ocular condition.
Treatment
The clinical trial involves the administration of **Atropine Sulfate 0.01% Ophthalmic Solution** as the experimental medication. This investigational product is formulated as eye drops, specifically a solution, and is intended for **ophthalmic use**. The active substance, **atropine sulfate**, is a muscarinic receptor antagonist. The solution is manufactured by OCUMENSION (HONG KONG) LIMITED. Participants will receive a maximum daily dose of 2 drops, with a total maximum dose of 2920 drops over a treatment period of 48 weeks. The administration schedule is designed to ensure consistent dosing, and participant compliance will be monitored throughout the study.
The trial also includes a **placebo** group, where participants will receive a placebo solution. This placebo is composed of the excipients used in the manufacture of the investigational drug but does not contain the active drug substance. The placebo is administered in the same pharmaceutical form as the experimental medication, ensuring that the study remains double-masked. The placebo is also administered via the ophthalmic route, maintaining consistency in the administration method across all study groups.
Efficacy
The efficacy of OT-101 (Atropine Sulfate 0.01% Ophthalmic Solution) in treating the progression of myopia in pediatric subjects will be assessed through a series of predefined endpoints over a 36-month period. The primary endpoint is the percentage of study eyes exhibiting a progression of myopia of -0.75 diopters (D) or greater, as determined by an increase in spherical equivalent of -0.75 D or more from baseline, assessed via cycloplegic autorefraction at Month 36.
Secondary endpoints include the change in spherical equivalent from baseline to Month 36, also measured by cycloplegic autorefraction, and the change in axial length of the study eye, measured by cycloplegic biometry. A consistent device will be used for biometry measurements throughout the study to ensure uniformity in data collection. These assessments will provide comprehensive data on the efficacy of the treatment in slowing the progression of myopia in the pediatric population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
- Be between 3-15 years of age of either sex and any race or ethnicity at Visit 1 (Day -14 to -1)
- 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
- Have anisometropia ≤ 1.0 D of spherical equivalent at Visit 1
- 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
- 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).
- 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
- Have known contraindications or sensitivity to atropine, the study medications, or their components
- 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
- 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
- Have any evidence of an eye movement disorder or restriction of extraocular movement (e.g., nystagmus)
- Have an active ocular infection (i.e., bacterial, viral, or fungal)
- 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
- Have a history of ocular herpetic infection, iritis, scleritis, or uveitis, whether active or inactive at screening
- 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
- 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
- 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
- Have had surgical intervention (ocular or systemic) within 6 months prior to Visit 1, or planned surgical intervention during the study
- 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.
- 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
- Participation in any other study of investigational therapy during the study period or within 30 Days before Visit 1
- Female subjects who are pregnant, nursing, or plan to become pregnant at any time during the study
- 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)
- Have a central nervous system disorder (e.g., epilepsy, cerebral disorders, Down syndrome)
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Hungary | Not Recruiting | 15 Dec 2021 | 59 |
 Ireland | Not Recruiting | 15 Dec 2021 | 50 |
 Poland | Not Recruiting | 15 Dec 2021 | 23 |
 Slovakia | Not Recruiting | 15 Dec 2021 | 29 |
 Spain | Not Recruiting | 15 Dec 2021 | 49 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Atropine Sulfate 0.01% Ophthalmic Solution | Test | EYE DROPS, SOLUTION | OPHTHALMIC USE | 2 | 48 | PRD11668996 |
The placebo for this trial will be composed of excipients used to manufacture the investigational drug but without the active drug substance. | Placebo | N/A | — | — | — | N/A |