Phase 3 Randomized, Double-Masked, Placebo-Controlled Study of Oxymetazoline Hydrochloride 0.1% Eye Drops for Acquired Blepharoptosis Treatment

Trial ID: 2024-513356-15-00
Protocol: 101380003SA
Sponsor: Santen

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Diseases & Conditions

Eyelid ptosis

Objectives

The primary objective of this study is to evaluate the **efficacy** of STN1013800, an eye drop solution containing oxymetazoline hydrochloride, when administered twice daily in the treatment of **acquired blepharoptosis** on Day 14. Acquired blepharoptosis, characterized by drooping of the upper eyelid, can impair vision and affect quality of life. Assessing the efficacy of this treatment is clinically relevant as it may offer a non-surgical option for managing this condition.

Secondary objectives include assessing the degree of improvement experienced by subjects since the start of the trial, as reported by the patients themselves (Patient Reported Outcome, PRO).

Participants

The clinical trial for the treatment of **acquired blepharoptosis** involves a total of 37 participants. The study population includes both male and female subjects aged between 18 and 75 years. Participants were selected based on specific criteria, including the presence of acquired ptosis in both eyes with a marginal reflex distance (MRD1) between 0 and 2 mm in the study eye, and a Snellen visual acuity of 20/80 or better in both eyes. The trial includes individuals who are able to self-administer the study treatment or have it administered by a caregiver. Participants must have a reliable visual field test and meet certain visual field loss criteria. The study population is not limited by general health status, but it does include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified in the trial data provided. The trial ensures that female participants of childbearing potential use acceptable contraception methods throughout the study period.

Plans and Procedures

The clinical trial is designed as a **randomized**, double-blind, placebo-controlled, multi-regional Phase III study to evaluate the efficacy and safety of STN1013800, an **oxymetazoline hydrochloride** 0.1% eye drop solution, in the treatment of **acquired blepharoptosis**. The trial aims to assess the primary endpoint of change from baseline in Marginal Reflex Distance 1 (MRD1) on Day 14, with a secondary endpoint of Patient Global Impression of Change (PGIC) on the same day. The study is expected to commence recruitment on November 1, 2024, and conclude by December 31, 2025, with a maximum treatment period of 42 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and visual acuity. Eligible participants will be randomly assigned to receive either the active treatment or a placebo. The study involves twice-daily administration of the eye drops, with follow-up visits scheduled to monitor safety and efficacy outcomes. The end-of-study visit will occur after the 14-day treatment period to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 42 days, including the screening period, treatment phase, and follow-up assessments. Conditions that may lead to early termination from the study include adverse events, non-compliance with the study protocol, or withdrawal of consent. Participants must be able to self-administer the treatment or have it administered by a caregiver and adhere to contraceptive requirements if applicable. The trial is not categorized as low intervention, and it does not involve a pediatric formulation.

Treatment

The clinical trial involves the administration of **STN1013800**, an experimental medication formulated as eye drops, solution. The active ingredient in STN1013800 is **oxymetazoline hydrochloride**, a chemical compound classified as an adrenergic agonist. The pharmaceutical form is specifically designed for ocular use. The medication is administered twice daily (BID) with a maximum daily dose of 0.2 mg and a total maximum dose of 8.4 mg over a treatment period of 42 days. The study aims to evaluate the efficacy and safety of this treatment in patients with acquired blepharoptosis.

In addition to the experimental treatment, a placebo comparator is utilized in the study. The placebo is designed to mimic the vehicle of the oxymetazoline hydrochloride eye drops but does not contain the active substance. The placebo is used to maintain the double-masked nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach allows for an unbiased assessment of the treatment's efficacy and safety.

Efficacy

The efficacy of STN1013800 (Oxymetazoline HCl 0.1% Eye Drops) in the treatment of acquired **blepharoptosis** will be assessed in a randomized, double-masked, placebo-controlled Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in Marginal Reflex Distance 1 (MRD1) on Day 14. MRD1 is defined as the distance between the upper eyelid margin and the center of the pupil, and its measurement will be conducted by a Central Reading Centre. The secondary endpoint involves a patient-reported outcome (PRO), specifically the Patient Global Impression of Change (PGIC) on Day 14.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Able to understand and sign an informed consent form prior to participation in any study-related procedures.
Male or female subjects ≥ 18 years.
Presence of all the following at Screening: a. diagnosis of acquired ptosis in both eyes with MRD 1 ≥0 and ≤ 2 mm in the study eye b. 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.

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Exclusion Criteria

Congenital ptosis.
Presence of either of the following: a. Pseudo ptosis (upper eyelid dermatochalasis that overhangs the upper eyelid margin); or b. 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 anti-glaucoma 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).
Resting heart rate (HR) outside the normal range (50–100 beats per minute).
Hypertension with resting diastolic blood pressure (BP) > 105 mm Hg or systolic BP > 180 mm Hg
Use of monoamine oxidase inhibitors (MAOIs; e.g., isocarboxazid, phenelzine, tranylcypromine) within 14 days prior to screening (Visit 1) and during the study.
Myasthenia gravis.
Advanced arteriosclerotic disease or history of cerebrovascular accident (CVA).
History of hyperthyroidism or thyroid eye disease (i.e., exophthalmos, upper eyelid retraction, diplopia secondary to extraocular muscle involvement). Hypothyroidism that is controlled on medication is allowed.
Subjects with proliferative diabetic retinopathy may not be enrolled. However, subjects with insulin dependent diabetes, diabetes requiring oral hypoglycemic drugs, or diet-controlled diabetes are allowed.
Pregnancy or lactation.
Diagnosed benign prostatic hypertrophy requiring medicinal therapy; previous prostatectomy is allowed.
History of contact or systemic allergic reaction to oxymetazoline hydrochloride or other sympathomimetic drugs (e.g., phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, fepradinol, or methoxamine, or any other diagnostic drugs intended to be used during the study period (e.g., Fluorescein, tropicamide etc.).
Participation in any drug or device clinical investigation within 30 days prior to screening (Visit 1) and/or during the period of study participation.
Planned use of prohibited concomitant medications during study.
Presence or history of any disease or condition that in the opinion of the Investigator may put the subject at significant risk or may confound study results or may interfere significantly with the subject’s participation in the study (e.g., uncontrolled cardiovascular disease, severe cardiovascular, respiratory, hepatobiliary, gastrointestinal, urology, renal, hematological, endocrine, immune, malignancy etc.).
Abuse or dependence of alcohol or drugs.
Any decision by the Investigator or Medical Monitor to terminate a subject in screening or declare any subject ineligible for any sound medical reason.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Recruiting	01 Nov 2024	32
Czechia	Recruiting	01 Nov 2024	60
France	Recruiting	01 Nov 2024	30
Germany	Not Recruiting	01 Nov 2024	10
Hungary	Recruiting	01 Nov 2024	41
Italy	Recruiting	01 Nov 2024	30
The Netherlands	Recruiting	01 Nov 2024	—
Poland	Recruiting	01 Nov 2024	50
Romania	Recruiting	01 Nov 2024	20
Spain	Recruiting	01 Nov 2024	40