Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% for the Treatment of Inflammation and Pain Associated With Cataract Surgery (CLOSE-1)
Condition: Cataract
MeSH terms: Cataract; Inflammation
Intervention: Clobetasol propionate; Vehicle
Intervention description: Clobetasol propionate ophthalmic nanoemulsion 0.05%, is an oil-in-water (o/w), clear or slightly yellowish nanoemulsion containing the active ingredient clobetasol propionate at a concentration of 0.05% weight per weight (w/w); Vehicle is identical in appearance and composition to clobetasol propionate ophthalmic nanoemulsion 0.05% but, without the active substance
Intervention MeSH terms: Clobetasol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: At least 210 participants will be randomized in a 2:1 randomization ratio (140 to clobetasol arm, 70 to placebo arm) in order to have 202 evaluable participants (4% lost to follow-up rate expected)
Masking: Double (Participant, Investigator)
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cataract surgery; Inflammation; Pain; Clobetasol propionate; Ophthalmology

Summary:

      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 participants 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%.
    

Eligibility criteria:

        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

               2. 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 investigational medical product
             (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, participants
             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 participant 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