A Randomised, Double-Masked, Placebo-Controlled Phase 3 Study on the Efficacy and Safety of STN1013800 (Oxymetazoline HCl 0.1% Eye Drops) used twice daily (BID) in the Treatment of Acquired Blepharoptosis

This is a randomised, double-masked, placebo-controlled Phase 3 study of the safety and efficacy of STN1013800 in the treatment of acquired blepharoptosis.

Subjects diagnosed with acquired blepharoptosis who meet eligibility criteria at Visit 1 (Screening) will return within 8 days for Visit 2 (Baseline, Day 1). At Visit 2 (Baseline, Day 1) they will be randomised to receive double-masked treatment for 6 weeks, with study visits completed at Week 2 (Day 14) and Week 6 (Day 42), and a post-treatment visit completed 2 weeks (± 3 days) after last study drug administration. Approximately 234 adult subjects with blepharoptosis who meet all the eligibility criteria will be randomised in a 1:1 ratio to receive:

• STN1013800 BID
• Placebo BID

Note that:

• On study visits Day 1 and Day 42, the AM dose is administered at 08:00 (at site) and the PM dose is administered at 16:00 (self-administered at home)
• On study visit Day 14, the AM dose is administered at 06:00 (self-administered at home), the PM dose is administered at 14:00 (at site)

Inclusion Criteria:

• Able to understand and sign an informed consent form prior to participation in any studyrelated procedures.

• Male or female subjects ≥ 18 years and ≤ 75 years.

• Presence of all the following at Screening:

  1. diagnosis of acquired ptosis in both eyes with MRD 1 ≥0 and ≤ 2 mm in the study eye
  2. Snellen VA of 20/80 or better in both eyes Note: MRD1 is defined as the distance between upper eye lid margin and centre of the pupil. MRD0 is defined as the upper eye lid margin at the centre of the pupil. Measurement of MRD1 will be done by a Central Reading Centre. If the centre of the pupil cannot be determined by the Central Reading Centre due to negative MRD1, the subject will be deemed ineligible.

• Females who are 1-year postmenopausal, surgically sterilised, or females of childbearing potential with a negative urine pregnancy test at screening (Visit 1). Females of childbearing potential must use an acceptable form of contraception throughout the study. Acceptable methods include the use of at least one of the following: intrauterine (intrauterine device), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence.

• A male subject with a female partner of childbearing potential should use or practice an acceptable contraceptive method, such as abstinence, condom or vasectomy (surgery at least 6 months prior to signing the study ICF and beginning screening), or other contraception deemed adequate by the investigator during the study.

• Able to self-administer study treatment or to have the study treatment administered by a caregiver throughout the study period.

• An answer of 'Yes' to the question 'Does the ptosis cause enough burden to the subject to want to receive treatment for it'.

• Loss of ≥ 8 points not seen at or above 10° from fixation in the superior visual field of a reliable HVF 36-point ptosis protocol test at screening visit in the same eye with MRD1 ≥0 and ≤ 2 mm. If both eyes have MRD1 ≥0 and ≤ 2 mm the more ptotic eye (the eye with the smaller MRD1 measurement) will be the study eye. If the MRD1 is the same in both eyes, the eye with the worse VF will be the study eye. If the MRD1 and VF is the same in both eyes, the right eye will be the study eye. The HVF Analyzer will determine if the visual field test is reliable. If the HVF Analyzer issues an "XX" for fixation losses, false positives, and/or false negatives, the test will be deemed unreliable. If deemed unreliable, the test must be retaken once per scheduled screening visit. If a reliable visual field cannot be obtained, the subject will be a screen failure.

Exclusion Criteria:

• In either eye:

• Congenital ptosis.

• Presence of either of the following:

  1. Pseudo ptosis (upper eyelid dermatochalasis that overhangs the upper eyelid margin); or
  2. Dermatochalasis that extends less than 3 mm above the upper eyelid margin.

• Neurogenic ptosis (e.g., Horner's syndrome, 3rd cranial nerve palsy).

• Myogenic ptosis.

• Marcus Gunn jaw-winking syndrome.

• Previous ptosis surgery (previous blepharoplasty is allowed provided the surgery took place at least 3 months prior to screening [Visit 1]).

• Lid position affected by lid or conjunctival scarring.

• Visual field loss from any cause other than ptosis.

• History of herpes keratitis.

• Poor fixation or abnormal eye position which prevents from taking reliable pictures for MRD1 measurement.

• History of closed/narrow angle glaucoma (unless patent peripheral iridotomy has been performed at least 3 months prior to screening (Visit 1).

• Facial including periocular neurotoxin (e.g., Botox, Xeomin, Dysport, Myobloc) injections within 3 months prior to screening (Visit 1) and during the study.

• Topical application of bimatoprost (i.e., Latisse®) to the eyelashes within 8 days prior to screening (Visit 1) and during the study.

• Mechanical ptosis e.g., ptosis due to orbital, corneal or lid tumor, cicatricial processes affecting the movements of the upper lid, and enophthalmos.

• Use of topical ophthalmic medications including anti-allergy [e.g., antihistamines], dry eye medications [e.g., IKERVIS®] (except artificial tears with anticipated stable usage during the study), antimicrobial drugs [e.g., antibiotics and antivirals], and anti-inflammatory drugs [including nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids] within 8 days prior to screening (Visit 1) and during the study. Timolol maleate, or sympathetic alpha receptor agonists (e.g., brimonidine tartrate, or apraclonidine hydrochloride) for the treatment of elevated intraocular pressure. Please note that topical ophthalmic prostaglandin analogues for the treatment of elevated intraocular pressure are permitted if dosed in the evening in accordance with the approved prescribing information. All other topical antiglaucoma medications are prohibited.

• Any intravitreal injections (e.g., antiVEGFs, steroids) within 8 days prior to screening (Visit

  1) and during the study.

• Current punctal plugs or placement of punctal plugs during the study.

• Current use of OTC vasoconstrictor/decongestant eye medication (e.g., Visine® L.R.®) or any ophthalmic or non-ophthalmic α-adrenergic agonist including OTC products (e.g., Afrin®) at any time during the study, (artificial tears are allowed).

• Monoamine oxidase inhibitors (MAOI) (e.g., selegiline hydrochloride, rasagiline mesilate, safinamide mesilate).

This is a double -masked study with subjects, Investigators, Site Staff, Reading Centre personnel, and Santen personnel involved in the conduct of the study all masked to the study treatment.

Each eligible subject will receive a numbered study treatment kit assigned by central randomisation via IWRS at Baseline.