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

NCT04246801 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CLOBOF3-16IA01
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 22

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%.

Conditions

Cataract

Keywords

Cataract surgery; Inflammation; Pain; Clobetasol propionate; Ophthalmology

Outcome Measures

Primary Outcomes (1)

• Anterior Chamber Cell Grade

  Percentage of participants with anterior chamber cell grade of "0" (absence of cells)

  Day 8

Secondary Outcomes (1)

• Pain Visual Analogue Scale (VAS) Score

  Day 8

Study Arms (2)

Clobetasol propionate

EXPERIMENTAL

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

Vehicle

PLACEBO COMPARATOR

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

Interventions

Clobetasol propionate DRUG

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)

Also known as: Clobetasol propionate ophthalmic nanoemulsion 0.05%, SVT-15473

Clobetasol propionate

Vehicle DRUG

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

Vehicle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 years or older on day of consent
• Participants with routine unilateral cataract surgery on the day prior to study randomization
• Participants with at least 5 cells in anterior chamber on the first day after surgery (at Baseline visit)
• Willing and able to understand and provide written informed consent form (ICF) (at Screening visit)
• Women who satisfy one of the following:
• 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),
• 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

You may not qualify if:

• Systemic administration of any corticosteroid or immunosuppressant drugs in the previous 2 weeks prior to the first instillation of the investigational medical product (IMP)
• 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)
• 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
• Prescription of any topical ocular medication, except preservative-free antibiotics for prophylactic purposes
• Any history of glaucoma or ocular hypertension in the study eye
• History or presence of endogenous uveitis
• Any current corneal abrasion or ulceration
• Any confirmed or suspected active viral, bacterial, or fungal keratoconjunctival disease
• Known hypersensitivity or contraindication to the study drug or any of its components
• History of steroid-related intraocular pressure (IOP) increase
• 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
• Presence of ocular hemorrhage which interferes with the evaluation of post-surgery inflammation
• 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
• 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)
• 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)

Sponsors & Collaborators

• Salvat: lead

Study Sites (22)

Arizona Eye Center

Chandler, Arizona, 85224, United States

Location

Beverly Hills Institute of Ophthalmology

Beverly Hills, California, 90210, United States

Location

Mark B. Kislinger, MD, Inc.

Glendora, California, 95670, United States

Location

LoBue Laseer & Eye Medical Center

Murrieta, California, 92562, United States

Location

Pasedena Eye Medical Group

Pasadena, California, 91105, United States

Location

Martel Medical Eye Group

Rancho Cordova, California, 95670, United States

Location

Santa Barbara Eyecare

Santa Barbara, California, 93105, United States

Location

Wolston & Goldberg Eye Associates

Torrance, California, 90505, United States

Location

Arus Research at Cape Coral Eye Center

Cape Coral, Florida, 33904, United States

Location

Dixon Eye Care

Albany, Georgia, 31701, United States

Location

Eye Care Centers Management, Inc. (Clayton Eye Center)

Morrow, Georgia, 30260, United States

Location

Coastal Research Associates

Roswell, Georgia, 30076, United States

Location

Chicago Eye Specialists

Chicago, Illinois, 60619, United States

Location

Chicago Cornea Consultants Ltd

Hoffman Estates, Illinois, 60169, United States

Location

Silverstein Eye Centers

Kansas City, Missouri, 64133, United States

Location

Wellish Vision Institute

Las Vegas, Nevada, 89119, United States

Location

Fifth Avenue Eye Associates

New York, New York, 10028, United States

Location

Apex Eye

Mason, Ohio, 45014, United States

Location

Black Hills Regional Eye Institute

Rapid City, South Dakota, 57701, United States

Location

Texan Eye, PA / Keystone Research Ltd.

Austin, Texas, 78731, United States

Location

Houston Eye Associates

Houston, Texas, 77025, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Related Publications (11)

• 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.

  PMID: 22133988 BACKGROUND

• Coppens M, Versichelen L, Mortier E. Treatment of postoperative pain after ophthalmic surgery. Bull Soc Belge Ophtalmol. 2002;(285):27-32.

  PMID: 12442340 BACKGROUND

• 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.

  PMID: 23608571 BACKGROUND

• Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. 2013;2(2):47-64. doi: 10.5497/wjp.v2.i2.47.

  PMID: 25590022 BACKGROUND

• 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. doi: 10.1016/s1350-9462(97)00002-5.

  PMID: 9537794 BACKGROUND

• 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. doi: 10.1016/j.ajo.2005.03.057.

  PMID: 16196117 BACKGROUND

• Chiquet C, Aptel F, Creuzot-Garcher C, Berrod JP, Kodjikian L, Massin P, Deloche C, Perino J, Kirwan BA, de Brouwer S, Combette JM, Behar-Cohen F. Postoperative Ocular Inflammation: A Single Subconjunctival Injection of XG-102 Compared to Dexamethasone Drops in a Randomized Trial. Am J Ophthalmol. 2017 Feb;174:76-84. doi: 10.1016/j.ajo.2016.10.012. Epub 2016 Nov 1.

  PMID: 27810317 RESULT

• Henzler D, Kramer R, Steinhorst UH, Piepenbrock S, Rossaint R, Kuhlen R. Factors independently associated with increased risk of pain development after ophthalmic surgery. Eur J Anaesthesiol. 2004 Feb;21(2):101-6. doi: 10.1017/s0265021504002042.

  PMID: 14977340 RESULT

• Kessel L, Tendal B, Jorgensen KJ, Erngaard D, Flesner P, Andresen JL, Hjortdal J. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review. Ophthalmology. 2014 Oct;121(10):1915-24. doi: 10.1016/j.ophtha.2014.04.035. Epub 2014 Jun 14.

  PMID: 24935281 RESULT

• Juthani VV, Clearfield E, Chuck RS. Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery. Cochrane Database Syst Rev. 2017 Jul 3;7(7):CD010516. doi: 10.1002/14651858.CD010516.pub2.

  PMID: 28670710 RESULT

• Sherif Z, Pleyer U. Corticosteroids in ophthalmology: past-present-future. Ophthalmologica. 2002 Sep-Oct;216(5):305-15. doi: 10.1159/000066189. No abstract available.

  PMID: 12424394 RESULT

MeSH Terms

Conditions

Cataract; Inflammation; Pain

Interventions

Clobetasol

Condition Hierarchy (Ancestors)

Lens Diseases; Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Betamethasone; Steroids, Fluorinated; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Laboratorios Salvat, S.A

ejimenez@svt.com

+34933946400

Study Officials

• Andrew Schwartz, MD

  Director of refractive surgery and laser vision correction at 5th Avenue Eye Associates

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: January 29, 2020
• Study Start: June 10, 2020
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: December 22, 2022
• Results First Posted: December 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)