Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% for the Treatment of Inflammation and Pain Associated With Cataract Surgery (CLOSE-2)

A Phase 3, Multicenter, Randomized, Double-Masked Clinical Trial to Assess the Efficacy and Safety of Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% Compared to Placebo in the Treatment of Inflammation and Pain Associated With Cataract Surgery

Cataract surgery is one of the most common surgical procedures performed worldwide. In fact, in 2017, 3.8 million cataracts procedures were performed in the US.

Despite of surgical advances, pain and inflammation after ophthalmic surgery continues to be a burden on both patients and physicians. The treatment of postoperative pain is essential for hospitalized patients, but it is even more important for patients who are treated on an outpatient basis.

This study will compare the efficacy and safety of clobetasol propionate ophthalmic nanoemulsion 0.05% to placebo, when administering one drop four times a day during 14 days after routine unilateral cataract surgery. Participants will undergo routine cataract surgery according to the ophthalmologist's normal procedures.

Overall, 210 participants are planned to take part in the study. They will be screened across 20 centers in the US. Participants who experience postoperative inflammation on the first day following routine cataract surgery and who meet all other eligibility criteria will be randomly assigned by chance to one of two study groups in a 2:1 ratio to receive either clobetasol propionate ophthalmic nanoemulsion 0.05 % (N=140) or placebo (N=70) for the treatment of inflammation and pain associated with cataract surgery.

Six (6) study visits are planned: Visit -1 (Screening), Visit 1 (Baseline; 24h after the surgery), Visit 2 (Day 3), Visit 3 (Day 8), Visit 4 (Day 15), and Visit 5 (Day 29).

The ophthalmologist will administer the first dose of the study medication 24 hours after the surgery, at the end of the Baseline visit, at the study center. Study medication will be then dispensed to patients for self-administration during the study at a dosage of one drop four times a day, during 14 days.

Direct instillation is the most efficient method for delivery to the ocular surface and is an accepted and widely used method for topical application to the eye. This study will examine effect and tolerability for 14 days of clobetasol propionate ophthalmic nanoemulsion 0.05% dosed four times a day.

This study is being conducted to support an application for approval to market clobetasol propionate ophthalmic nanoemulsion 0.05% in the US for the indication of inflammation and pain after ocular surgery. The reference (comparator) product in this study, the vehicle, is expected to provide a lower efficacy rate when compared to clobetasol 0.05%.

Inclusion Criteria:

1. Male or female, age 18 years or older on day of consent

2. Participants with routine unilateral cataract surgery on the day prior to study randomization

3. Participants with at least 5 cells in anterior chamber on the first day after surgery (at Baseline visit)

4. Willing and able to understand and provide written informed consent form (ICF) (at Screening visit)

5. Women who satisfy one of the following:

   1. Are of child-bearing potential who are not pregnant or lactating and who are either abstinent or sexually active on an acceptable method of birth control (methods that can achieve a failure rate of less than 1% per year when used consistently and correctly, like hormonal contraception (oral pills, implantable device, or skin patch), intrauterine device, bilateral tubal occlusion, or double barrier) for at least 4 weeks prior to Baseline visit and throughout the study (i.e., until Day 29),

OR

Are post-menopausal (have had no menstrual cycle for at least one year prior to Screening visit) or have undergone a sterilization procedure (bilateral tubal ligation, hysterectomy, hysterectomy with unilateral or bilateral oophorectomy or bilateral oophorectomy) at least 6 months prior to Screening visit

Exclusion Criteria:

1. Systemic administration of any corticosteroid or immunosuppressant drugs in the previous 2 weeks prior to the first instillation of the investigational medical product (IMP)
2. Periocular injection in the study eye of any corticosteroid solution within 4 weeks prior to the first instillation of the IMP, or of any corticosteroid depot within 2 months prior to the first instillation of the IMP (Ozurdex® [dexamethasone]: within prior 6 months; Iluvien® [fluocinolone]: within prior 36 months)
3. Instillation of any topical ocular corticosteroid, non-steroidal antiinflammatory drug (NSAID), mast cells stabilizers, antihistamines or decongestants within 2 weeks prior to the first instillation of the IMP, except pre-surgical and/or surgical administration of 1 drop of a topical NSAID or corticosteroid, at the investigator discretion
4. Prescription of any topical ocular medication, except preservative-free antibiotics for prophylactic purposes
5. Any history of glaucoma or ocular hypertension in the study eye
6. History or presence of endogenous uveitis
7. Any current corneal abrasion or ulceration
8. Any confirmed or suspected active viral, bacterial, or fungal keratoconjunctival disease
9. Known hypersensitivity or contraindication to the study drug or any of its components
10. History of steroid-related intraocular pressure (IOP) increase
11. Previous surgery in the last 4 weeks prior to the Screening visit or new surgery scheduled to be performed before the end of the study period on the contralateral eye
12. Presence of ocular hemorrhage which interferes with the evaluation of post-surgery inflammation
13. Presence of intraoperative complications during the cataract surgical procedure that may increase post-operative inflammation; this includes, in particular, patients with ocular hemorrhage, floppy iris syndrome, increased IOP (≥24 mmHg), posterior capsule rupture and injections of gas into the vitreous body
14. Increased cumulative dissipated energy value during phacoemulsification (increased energy used for phacoemulsification exert additional stress on iris and other anterior chamber structures and may generate excessive inflammation)
15. Presence of zonular dialysis (rupture of zonular fibers that attach lens to the ciliar body which may lead to partial luxation of the lens / lens capsule and is a serious complication of cataract surgery)
16. Presence of Fuchs´ endothelial dystrophy (loss of endothelial cells that may result in chronic corneal edema after cataract surgery especially if high energy was used during phacoemulsification)
17. Presence of cornea guttata
18. Pupil dilation lower than 4.5 mm
19. Presence of lower lacrimal duct obstruction and/or history of infectious dacryocystitis
20. Presence of IOP ≥24 mmHg at Baseline visit
21. Participation in any study of an investigational topical or systemic new drug or device within 30 days prior to the Screening visit, or at any time during the study
22. Prior participation in the study described in this protocol, unless patient was not randomized
23. In the opinion of the investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops
24. Disease, condition (including monocular participants), or disorder that in the judgement of investigator could confound study assessments or limit compliance to study protocol