Clinical trial NCT03942419: Microdosed Atropine 0.1% and 0.01% Ophthalmic Solutions for Reduction of Pediatric Myopia Progression
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myopia
Lead sponsor: Eyenovia Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-08
Enrollment: 438
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi-center, double masked, randomized, placebo-controlled study evaluating the efficacy of microdosed atropine 0.01%, atropine 0.1% and placebo ophthalmic solutions. Subjects will administer their assigned medication daily in both eyes for 36 months, then be re-randomized to the same or an alternative treatment arm and followed for an additional 12 months.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Myopia progression
timeFrame: 36 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Optometry
state: Alabama
city: Glendale
country: United States
facility: Midwestern University
state: Arizona
city: Azusa
country: United States
facility: Canyon City Eyecare
state: California
city: Berkeley
country: United States
facility: UC Berkeley
state: California
city: Los Angeles
country: United States
facility: Marshall Ketchum University College of Optometry
state: California
city: San Diego
country: United States
facility: Ratner Children's Eye Center
state: California
city: Chicago
country: United States
facility: Illinois College of Optometry
state: Illinois
city: Downers Grove
country: United States
facility: Midwestern University
state: Illinois
city: New York
country: United States
facility: SUNY College of Optometry
state: New York
city: High Point
country: United States
facility: Wake Forest Health Network Ophthalmology - Oak Hollow
state: North Carolina
city: Raleigh
country: United States
facility: Oculus Research
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University - College of Optometry
state: Ohio
city: Cranberry Township
country: United States
facility: Scott & Christie and Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Salus University - The Eye Institute
state: Pennsylvania
city: Brentwood
country: United States
facility: Primary Eyecare Group
state: Tennessee
city: Memphis
country: United States
facility: Southern College of Optometry
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Virginia Beach
country: United States
facility: Virginia Pediatric Eye Center
state: Virginia
Study officials:
References: