Microdosed Atropine 0.1% and 0.01% Ophthalmic Solutions for Reduction of Pediatric Myopia Progression

A Multicenter, Double-Masked, Randomized, Placebo-Controlled Phase 3 Study of the Safety and Efficacy of Atropine 0.1% and 0.01% Ophthalmic Solutions Administered With a Microdose Dispenser for the Reduction of Pediatric Myopia Progression (The CHAPERONE Study)

This study evaluates the progression of myopia in participants using microdosed atropine 0.01%, atropine 0.1%, or placebo ophthalmic solution. Eligible subjects will administer study medication daily in each eye for 48 months. Efficacy and safety assessments will be performed at visits scheduled for 1, 6, 12, 18, 24, 30 and 36 months after initiation of medication use. Subjects will be re-randomized at the 36 month visit, then followed at 6 month intervals for an additional year.

Study Overview

• Status: Terminated
• Conditions: Myopia
• Intervention / Treatment: Drug: Atropine 0.1% Ophthalmic Solution; Drug: Atropine 0.01% Ophthalmic Solution; Drug: Placebo Ophthalmic Solution

Detailed Description

Subjects will be evaluated for eligibility during an initial Screening Visit and enrolled after signing the study-specific informed consent form(s). Eligible subjects must complete a run-in period where they use the microdose dispenser to administer study drug "vehicle" solution daily in both eyes. After run-in, subjects return for a Baseline Visit and additional study eligibility assessments. Subjects who continue to be eligible will be equally randomized to one of the following treatment groups:

• Microdose atropine 0.1% ophthalmic solution
• Microdose atropine 0.01% ophthalmic solution
• Microdose placebo ophthalmic solution

Randomization will be stratified by iris color (e.g., dark and light) and study site. Study enrollment will be limited to a maximum of 50% of subjects who self-identify as East Asian ethnicity. Subjects will use their assigned study medication daily in both eyes and return for efficacy and safety assessments at 1, 6, 12, 18, 24, 30, and 36 months.

At the Month 36 Visit, subjects in the 2 atropine dose arms will be re-randomized to either placebo or 1 of the 2 doses of atropine ophthalmic solution, while subjects originally assigned to placebo will be re-randomized to one of the 2 atropine ophthalmic solution arms. After re-randomization, all subjects will be followed for an additional year with efficacy and safety examinations at Months 42 and 48.

• Study Type: Interventional
• Enrollment (Actual): 438
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham School of Optometry
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Midwestern University
  • California
    • Azusa, California, United States, 91702
      • Canyon City Eyecare
    • Berkeley, California, United States, 94720
      • UC Berkeley
    • Los Angeles, California, United States, 90037
      • Marshall Ketchum University College of Optometry
    • San Diego, California, United States, 92093
      • Ratner Children's Eye Center
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Illinois College of Optometry
    • Downers Grove, Illinois, United States, 60515
      • Midwestern University
  • New York
    • New York, New York, United States, 10036
      • SUNY College of Optometry
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Wake Forest Health Network Ophthalmology - Oak Hollow
    • Raleigh, North Carolina, United States, 27603
      • Oculus Research
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University - College of Optometry
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott & Christie and Associates
    • Philadelphia, Pennsylvania, United States, 19141
      • Salus University - The Eye Institute
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
      • Primary Eyecare Group
    • Memphis, Tennessee, United States, 38104
      • Southern College of Optometry
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23452
      • Virginia Pediatric Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Refractive error by cycloplegic autorefraction: myopia -1.00 D to -6.00 D in both eyes; astigmatism ≤ 1.50 D in both eyes; anisometropia < 1.50 D.
• Best-corrected distance visual acuity in current correction of 0.2 logMAR or better with interocular difference ≤ 0.1 logMAR.
• Refractive correction for each eye meets the following criteria: myopia within ± 0.50 D of the manifest refraction at the Screening Visit; cylinder power within ± 0.50 D of the manifest refraction at the Screening Visit; when cylinder power is < 1.00 D, axis within ± 15 degrees of the manifest refraction; when cylinder power is ≥ 1.00 D, axis within ± 5 degrees of the manifest refraction.

Exclusion Criteria:

• Current or previous myopia treatment with non-study atropine, pirenzepine or other topical anti-muscarinic agent.
• Current use of bifocals, progressive-addition lenses, or multifocal soft contact lenses.
• Use of rigid gas permeable lenses, including orthokeratology lenses within 90 days of Screening.
• Known atropine allergy.
• Abnormality of the cornea, lens, central retina, iris or ciliary body.
• Current or prior history of manifest strabismus, amblyopia, or nystagmus.
• Prior eyelid, strabismus, intraocular, or refractive surgery.
• Intraocular pressure > 26 mmHg.
• History of premature birth by parent's report.
• Inability to perform protocol-prescribed testing due to preexisting neurological diagnoses, genetic syndrome, or other issues.
• Medical conditions predisposing patient to degenerative myopia, abnormal ocular refractive anatomy, and/or any history of intraocular surgery.
• Any systemic disease or condition that may affect visual function or development such as diabetes mellitus.
• Any ocular inflammation or external ocular inflammation within 30 days of Screening.
• History of punctal occlusion.
• Heterochromia.
• Lid squeezers.
• Participation in any study of an investigational, interventional product within 30 days prior to Screening Visit.
• Immediate family member of study staff designed to perform study evaluations or procedures.
• Pregnancy, or if sexually active, unwillingness to use an acceptable form of contraception during the study.
• Presence of a severe/serious ocular condition or any other unstable medical condition that, in the Investigator's opinion, may preclude study treatment or follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atropine 0.1% Ophthalmic Solution; Atropine 0.1% ophthalmic solution administered daily in both eyes using a microdose dispenser	Drug: Atropine 0.1% Ophthalmic Solution; Atropine 0.1% ophthalmic solution administered with a microdose dispenser
Experimental: Atropine 0.01% Ophthalmic Solution; Atropine 0.01% ophthalmic solution administered daily in both eyes using a microdose dispenser	Drug: Atropine 0.01% Ophthalmic Solution; Atropine 0.01% ophthalmic solution administered with a microdose dispenser
Placebo Comparator: Placebo Ophthalmic Solution; Placebo ophthalmic solution administered daily in both eyes using a microdose dispenser	Drug: Placebo Ophthalmic Solution; Placebo ophthalmic solution administered with a microdose dispenser

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myopia progression	The proportion of primary study eyes showing less than 0.50 D (spherical equivalent) myopia progression compared to baseline measured using cycloplegic autorefraction.	36 Months

Collaborators and Investigators

• Sponsor: Eyenovia Inc.
• Investigators: Study Director: Daniel Donatello, Bausch & Lomb Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Mydriatics; Pharmaceutical Solutions; Atropine; Ophthalmic Solutions
• Other Study ID Numbers: EYN-MYO-AT-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No