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

Sponsor
Salvat (Industry)
Overall Status
Completed
CT.gov ID
NCT04249076
Collaborator
(none)
215
Enrollment
18
Locations
2
Arms
10.3
Actual Duration (Months)
11.9
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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 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%.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
215 participants
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)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)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jun 4, 2020
Actual Primary Completion Date :
Apr 14, 2021
Actual Study Completion Date :
Apr 14, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Clobetasol propionate

First dose of the drug will be dispensed at the end of the Baseline visit at the study center. Then, study medication will be dispensed to the participant for self-administration at a dosage ofe one drop four (4) times a day during 14 days

Drug: Clobetasol Propionate
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)
Other Names:
  • Clobetasol propionate ophthalmic nanoemulsion 0.05%
  • SVT-15473
  • Placebo Comparator: Vehicle

    First dose of the drug will be dispensed at the end of the Baseline visit at the study center. Then, study medication will be dispensed to the participant for self-administration at a dosage ofe one drop four (4) times a day during 14 days

    Drug: Vehicle
    Vehicle is identical in appearance and composition to clobetasol propionate ophthalmic nanoemulsion 0.05% but, without the active substance

    Outcome Measures

    Primary Outcome Measures

    1. Anterior chamber cell grade [Day 8]

      Proportion of participants with anterior chamber cell grade of "0" (absence of cells) compared to placebo

    Secondary Outcome Measures

    1. Pain Visual Analogue Scale (VAS) score [Day 8]

      Proportion of participants with VAS pain score of "0" (no eye pain) compared to placebo. VAS is a continuous scale comprised of an horizontal line 10 centimeters in length. Score of 0 represents "No eye pain" and score of 10 represents "Worst imaginable eye pain"

    2. Anterior chamber cell grade [Day 3, Day 15 and Day 29]

      Proportion of participants with anterior chamber cell grade of "0" compared to placebo

    3. Anterior chamber cell grade [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline, in the proportion of participants with different anterior chamber cell grades, compared to placebo

    4. Anterior chamber flare grade [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline, in the proportion of participants with different anterior chamber flare grades, compared to placebo

    5. Anterior chamber cell grade and anterior chamber flare grade [Day 3, Day 8, Day 15 and Day 29]

      Proportion of participants with anterior chamber cell grade of "≤0.5+" and flare grade of "0" compared to placebo

    6. Anterior chamber cell grade [Day 3, Day 8, Day 15 and Day 29]

      Proportion of participants with anterior chamber cell grade of "≤1+" compared to placebo

    7. Anterior chamber cell grade and anterior chamber flare grade [Day 3, Day 8, Day 15 and Day 29]

      Proportion of participants with anterior chamber cell grade of "0" and flare grade of "0" compared to placebo

    8. Frequency of signs of ocular inflammation [Baseline, Day 3, Day 8, Day 15 and Day 29]

      Frequency of different signs of ocular inflammation compared to placebo

    9. Proportion of signs of ocular inflammation [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline, in the proportion of participants with different signs of ocular inflammation compared to placebo

    10. Severity of signs of ocular inflammation [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline in the severity of signs of ocular inflammation compared to placebo

    11. Photophobia Visual Analogue Scale (VAS) score [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline, in the photophobia VAS score compared to placebo. VAS is a continuous scale comprised of an horizontal line 10 centimeters in length. Score of 0 represents "No photophobia" and score of 10 represents "Worst imaginable photophobia"

    12. Best-Corrected Visual Acuity (BCVA) letters score [Day 8, Day 15 and Day 29]

      Change from Baseline, in Snellen BCVA letters score compared to placebo. Visual acuity is measured according to the size of letters viewed on the Snellen chart. "Normal" visual acuity is 20/20 score

    13. Pain Visual Analogue Scale (VAS) score [Day 3, Day 8, Day 15 and Day 29]

      Change from Baseline, in the pain/discomfort VAS score compared to placebo. VAS is a continuous scale comprised of an horizontal line 10 centimeters in length. Score of 0 represents "No eye pain" and score of 10 represents "Worst imaginable eye pain"

    14. Pain Visual Analogue Scale (VAS) score [Day 3, Day 15 and Day 29]

      Proportion of patients with VAS pain of "0" compared to placebo. VAS is a continuous scale comprised of an horizontal line 10 centimeters in length. Score of 0 represents "No eye pain" and score of 10 represents "Worst imaginable eye pain"

    15. Discomfort severity assessment [Day 3, Day 8, Day 15 and Day 29]

      Change from baseline in the discomfort grade compared to placebo. The severity of the eye discomfort will be done by using an assessment scale where grade "0" is "None" (no discomfort); grade "1" is "Mild dicomfort"; grade "2" is "Moderate discomfort"; and grade "3" is "Severe discomfort"

    16. Discomfort severity assessment [Day 3, Day 8, Day 15 and Day 29]

      Proportion of participants with no discomfort (grade "0" or "None") compared to placebo. The severity of the eye discomfort will be done by using an assessment scale where grade "0" is "None" (no discomfort); grade "1" is "Mild dicomfort"; grade "2" is "Moderate discomfort"; and grade "3" is "Severe discomfort"

    17. Pain Visual Analogue Scale (VAS) score [From Baseline and up to 14 days]]

      Change in the VAS oain score reported in the patient´s diaries compared to placebo. VAS is a continuous scale comprised of an horizontal line 10 centimeters in length. Score of 0 represents "No eye pain" and score of 10 represents "Worst imaginable eye pain"

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    6. 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Walman Eye CenterSun CityArizonaUnited States85225
    2Inland Eye SpecialistsHemetCaliforniaUnited States92595
    3United Medical Research InstituteInglewoodCaliforniaUnited States90301
    4Visionary Eye InstituteNewport BeachCaliforniaUnited States92663
    5North Bay EyePetalumaCaliforniaUnited States94954
    6Levenson Eye AssociatesJacksonvilleFloridaUnited States32204
    7International Eye Associates, PAOrmond BeachFloridaUnited States32174
    8Andrew Gardner Logan dba Ophthalmic Research LLCTamaracFloridaUnited States33321-2934
    9Eye Consultants of AtlantaAtlantaGeorgiaUnited States30339
    10Kannarr Eye CarePittsburgKansasUnited States66762
    11Ophalmology AssociatesSaint LouisMissouriUnited States63131
    12Comprehensive Eye Care LtdWashingtonMissouriUnited States63090
    13NV Eyey SurgeryHendersonNevadaUnited States89052
    14Houston Eye AssociatesHoustonTexasUnited States77008
    15Shah Eye CenterMissionTexasUnited States78572-2424
    16Braverman-Terry-Oei Eye AssociatesSan AntonioTexasUnited States78212
    17Stacy R. Smith, M.D., P.C.Salt Lake CityUtahUnited States84117-5209
    18Virgina Eye ConsultantsNorfolkVirginiaUnited States23512

    Sponsors and Collaborators

    • Salvat

    Investigators

    • Principal Investigator: Andrew Schwartz, MD, Director of refractive surgery and laser vision correction at 5th Avenue Eye Associates

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Salvat
    ClinicalTrials.gov Identifier:
    NCT04249076
    Other Study ID Numbers:
    • CLOBOF3-16IA02
    First Posted:
    Jan 30, 2020
    Last Update Posted:
    Oct 18, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Salvat
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 18, 2021