Childhood Atropine for Myopia Progression (CHAMP): A 3-Arm Randomized,
Double-Masked, Placebo-Controlled, Phase 3 Study of Atropine Sulfate Ophthalmic Solution 0.01%
and 0.02%

Ametropia in children is common, and if left uncorrected causes decreased
vision, visual
discomfort (eye strain), strabismus, and/or amblyopia (AAPOS 2013). The most
common form
of refractive error is myopia (nearsightedness), which has its onset in
children 6 to 12 years of
age (Zadnik 2015). The American Association for Pediatric Ophthalmology and
Strabismus
(AAPOS) and American Academy of Ophthalmology (AAO) Joint Policy Statement in
2013
reports that it is important that myopia be addressed early in life because, in
addition to
correcting imperfect vision, good vision is essential for proper physical
development and
educational progress in growing children. If a growing child's eye does not
provide a clear,
focused image to the developing brain, irreversible loss of vision in one or
both eyes may result
(AAPOS 2013).

There are currently no Food and Drug Administration (FDA)-approved drug
products to treat the
progression of myopia in children. Topical ophthalmic drugs such as 1% atropine
and
2% pirenzepine (both antimuscarinic agents) have been shown to slow myopia
progression
(Brodstein 1984; Yen 1989; Chua 2006; Fan 2007; Yi 2015); however, pirenzepine
is not FDA
approved for ophthalmic use, and although 1% atropine is approved by the FDA
for topical
ocular use (cycloplegia, mydriasis, and penalization of the healthy eye in the
treatment of
amblyopia), it is not approved to slow the progression of myopia. Further,
treatments such as
orthokeratology and the use of multifocal lenses have been used as therapy to
slow the
progression of myopia in children, however, neither has shown efficacy
equivalent to that of
antimuscarinic agents (Walline 2011).

Recent reviews (Walline 2011; Huang 2016; Gong 2017) have concluded that
antimuscarinic
topical medication is an effective treatment to slow myopia progression.

Primary Objective: To evaluate the safety and efficacy of 2 concentrations of
Atropine Sulfate Ophthalmic
Solution (0.01% and 0.02%) compared to Vehicle (placebo) for slowing the
progression of myopia in
children over a 3-year treatment period.
Exploratory Objective: To observe safety and efficacy in subjects re-randomized
to 1 year of treatment with
Atropine Sulfate Ophthalmic Solution, 0.01% or 0.02%, or Vehicle following 3
years of treatment in
children with progressive myopia.

This will be a 3-arm randomized, multicenter, double-masked, placebo-controlled
study
conducted in 2 stages. Stage 1 is a safety and efficacy phase of 3 years (36
months) in duration,
during which subjects will be allocated 1 of 3 study medications. Stage 2 is a
randomized
cross-over phase of 1 year (12 months) in duration, during which subjects will
be re-randomized
to receive 1 of the 3 study medications with subjects initially randomized to
Vehicle only eligible
for randomization to 0.01% or 0.02% Atropine Sulfate Ophthalmic Solution.
Subjects (aged 3 to
<= 17.0 years) will enter the study with myopia SER of at least -0.50 D and no
greater than -6.00
D myopia in each eye as measured by cycloplegic autorefraction, and following
successful
eligibility screening at the Screening/Baseline visit will be randomized to one
of the following 3
treatment groups in a 2:2:3 ratio:
* Vehicle (placebo) (N = 138)
* Atropine Sulfate Ophthalmic Solution, 0.01% (N = 138)
* Atropine Sulfate Ophthalmic Solution, 0.02% (N = 207)

The allocated study medication will be administered, one drop in each
eye once daily (QD), at bedtime, for 3 years.
Treatment arms are:
* Atropine Sulfate Ophthalmic Solution, 0.01%
* Atropine Sulfate Ophthalmic Solution, 0.02%
* Vehicle (placebo)

The subject's myopia may or may not get worse while taking part in this study.
The results of this study may help children with myopia in the future. If
Atropine eye drops are effective in treating the progression of myopia,
participants receiving placebo may not receive the same benefit as those who
receive the active drug.

SIDE EFFECTS THAT MAY OCCUR WHILE USING ATROPINE SULFATE:
• Eye discomfort
• Glare
• Blurred near vision
• Light sensitivity
• Pain and stinging at time of drop
• Inflammation of the cornea (clear layer on the front of the eye)
• Dry eye
• Redness and swelling of the eye or eyelid
• Irritability
• Fast heart beat
• Restlessness
• Dryness of skin, mouth or throat
• Flushed skin on face and neck

There may be other risks or side effects of Atropine eye drops that are unknown
at this time. Allergic reactions can occur with any drug.

POSSIBLE RISKS OR SIDE EFFECTS OF THE STUDY PROCEDURES
Possible risks of numbing drops
The numbing drops that are used for checking the eye pressure may sting for a
few seconds when they are first placed in the eyes. It is important that the
subjects don*t rub their eyes while they are numb to avoid scratching the
surface of the eyes.

Possible risks of dilating drops
The drops used to dilate the eyes may sting when they are first placed in the
eyes. They may cause blurry vision for a few hours, especially thereading
vision, and cause sensitivity to light. To protect the eyes and minimize
discomfort, the subject should wear sunglasses while outside, until the effects
of the drops wear-off.