Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% for the Treatment of Inflammation and Pain Associated With Cataract Surgery (CLOSE-1)

• Sponsor: Salvat (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04246801
• Collaborator: (none)
• Enrollment: 212
• Locations: 22
• Arms: 2
• Actual Duration (Months): 11.3
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.9

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 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%.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Drug: Clobetasol propionate; Drug: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 212 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 10, 2020
• Actual Primary Completion Date: May 19, 2021
• Actual Study Completion Date: May 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clobetasol propionate Clobetasol propionate (Clobetasol propionate ophthalmic nanoemulsion 0.05%) 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 of 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 of 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 the 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 the 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 [Day 3, Day 8, Day 15 and Day 29]

   Frequency of different signs of ocular inflammation compared to placebo at Baseline

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 the 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 the 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 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 participants 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 Mild discomfort; grade 2 Moderate discomfort; and grade 3 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 Mild discomfort; grade 2 Moderate discomfort; and grade 3 Severe discomfort.

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

    Change in the VAS pain score reported in the patients' 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

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Eye Center	Chandler	Arizona	United States	85224
2	Beverly Hills Institute of Ophthalmology	Beverly Hills	California	United States	90210
3	Mark B. Kislinger, MD, Inc.	Glendora	California	United States	95670
4	LoBue Laseer & Eye Medical Center	Murrieta	California	United States	92562
5	Pasedena Eye Medical Group	Pasadena	California	United States	91105
6	Martel Medical Eye Group	Rancho Cordova	California	United States	95670
7	Santa Barbara Eyecare	Santa Barbara	California	United States	93105
8	Wolston & Goldberg Eye Associates	Torrance	California	United States	90505
9	Arus Research at Cape Coral Eye Center	Cape Coral	Florida	United States	33904
10	Dixon Eye Care	Albany	Georgia	United States	31701
11	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia	United States	30260
12	Coastal Research Associates	Roswell	Georgia	United States	30076
13	Chicago Eye Specialists	Chicago	Illinois	United States	60619
14	Chicago Cornea Consultants Ltd	Hoffman Estates	Illinois	United States	60169
15	Silverstein Eye Centers	Kansas City	Missouri	United States	64133
16	Wellish Vision Institute	Las Vegas	Nevada	United States	89119
17	Fifth Avenue Eye Associates	New York	New York	United States	10028
18	Apex Eye	Mason	Ohio	United States	45014
19	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
20	Texan Eye, PA / Keystone Research Ltd.	Austin	Texas	United States	78731
21	Houston Eye Associates	Houston	Texas	United States	77025
22	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240

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

• Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems--recent advances. Prog Retin Eye Res. 1998 Jan;17(1):33-58. Review.
• Coppens M, Versichelen L, Mortier E. Treatment of postoperative pain after ophthalmic surgery. Bull Soc Belge Ophtalmol. 2002;(285):27-32. Review.
• Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. Review.
• Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol. 2012 May;96(5):614-8. doi: 10.1136/bjophthalmol-2011-300539. Epub 2011 Dec 1. Review.
• Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. 2013;2(2):47-64.
• Porela-Tiihonen S, Kaarniranta K, Kokki H. Postoperative pain after cataract surgery. J Cataract Refract Surg. 2013 May;39(5):789-98. doi: 10.1016/j.jcrs.2013.03.012. Review.

• Responsible Party: Salvat
• ClinicalTrials.gov Identifier: NCT04246801
• Other Study ID Numbers: CLOBOF3-16IA01
• First Posted: Jan 29, 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: Cataract surgery; Inflammation; Pain; Clobetasol propionate; Ophthalmology
• Additional relevant MeSH terms: Cataract; Inflammation; Clobetasol

Study Results

No Results Posted as of Oct 18, 2021