SKYGGN: OCS-01 in Treating Inflammation and Pain in Post-cataract Patients

• Sponsor: Oculis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04130802
• Collaborator: (none)
• Enrollment: 153
• Locations: 4
• Arms: 3
• Actual Duration (Months): 4.1
• Patients Per Site: 38.3
• Patients Per Site Per Month: 9.2

Study Details

Study Description

Brief Summary

The DX-216 trial is a randomized, double-masked, placebo (vehicle)-controlled study evaluating the efficacy and safety of two doses of OCS-01 compared to vehicle in the treatment of inflammation and pain following cataract surgery. The primary objective is to evaluate the efficacy and safety of OCS-01 compared to placebo and the secondary objective is to evaluate the optimal dosing frequency (once a day [QD] or twice a day [BID]).

Condition or Disease	Intervention/Treatment	Phase
Inflammation Corneal; Pain, Postoperative	Drug: OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL; Drug: Placebo	Phase 2

Detailed Description

This is a multi-center, randomized, double-masked, placebo (vehicle)-controlled study, designed to evaluate the efficacy and safety of OCS-01 ophthalmic suspension (QD versus BID) compared to placebo in treating inflammation and pain following cataract surgery. Subjects will be randomized 1:1:1 to receive OCS-01 QD, OCS-01 BID, or placebo BID. Subjects will dose 1 drop in the study eye BID for 14 days, beginning 1 day post-surgery in the operated eye. The study will last up to 24 days, including a follow-up visit at Visit 7 (Day 22 ± 2).

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-masked, placebo (vehicle)-controlled study evaluating the efficacy and safety of two doses of OCS-01 compared to vehicleRandomized, double-masked, placebo (vehicle)-controlled study evaluating the efficacy and safety of two doses of OCS-01 compared to vehicle
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: For masking purposes, each dosing box and the pouches within it will be labeled either "AM" or "PM." Dosing boxes and pouches will be labeled this way regardless of whether the product within the 2 boxes is the same (i.e. OCS-01 BID and placebo treatment arms) or different (i.e. OCS-01 QD).
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-masked, Vehicle-controlled Study Evaluating the Efficacy and Safety of Two Doses of OCS 01 Compared to Vehicle in the Treatment of Inflammation and Pain Following Cataract Surgery
• Actual Study Start Date: Sep 27, 2019
• Actual Primary Completion Date: Jan 31, 2020
• Actual Study Completion Date: Jan 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OCS-01 1.5% mg/mL QD eye drops	Drug: OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL; OCS-01 eye drops; Other Names: DexNP ; Drug: Placebo; Vehicle eye drops; Other Names: Vehicle
Experimental: OCS-01 1.5% mg/mL BID eye drops	Drug: OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL; OCS-01 eye drops; Other Names: DexNP
Placebo Comparator: Placebo (Vehicle) BID eye drops	Drug: Placebo; Vehicle eye drops; Other Names: Vehicle

Outcome Measures

Primary Outcome Measures

1. Anterior Chamber Cells [at Day 15 (visit 6)]

   Absence of anterior chamber cells as measured by slit beam with fluoresceine The outcome measure was the number of subjects with an absence of anterior chamber cells

2. Ocular Pain [at Day 4 (visit 4)]

   Absence of pain as assessed by Ocular Pain Grading Scale (Min 0, Max 10) in which 0 is no pain and 10 is the worst possible. Outcome measure was the number of subjects who reported no pain

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Provide written informed consent, approved by the appropriate ethics committee;

2. Be able to comply with the study requirements and visit schedule;

3. Be at least 18 years of age of either sex or any race;

4. Be planning to undergo unilateral cataract extraction via phacoemulsification and PCIOL implantation in the study eye;

5. Have an anterior chamber cell score ≥ 2 at Visit 2 (Day 1 [18 to 30 hours post-uncomplicated cataract surgery without vitreous loss]);

6. Have a pin-hole visual acuity (VA) without any other correction > 20 letters (approximately 20/400) in the operative eye and > 35 letters (approximately 20/200) in the fellow eye as measured using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart at Visit 1 (Day -1 to Day -28 [prior to surgery]);

7. Have a negative urine pregnancy test at Visit 1 (Day -1 to Day -28 [prior to surgery]),

Exclusion Criteria:

1. Have a known sensitivity or allergy to dexamethasone, corticosteroids, or any of the study medication's components;

2. Be monocular;

3. Have any intraocular inflammation (e.g. white blood cells or flare) present in either eye at the Visit 1 (Day -1 to Day -28 [prior to surgery]) slit lamp examination;

4. Have a score > 0 on the Ocular Pain Assessment at Visit 1 (Day -1 to Day -28 [prior to surgery]) in the study eye;

5. Use anti-inflammatory agents, analgesics/pain relievers (including opioids, narcotics, and other pain medications), or immunomodulating agents, systemically or in either eye, and/or use medications for benign prostatic hyperplasia (BPH), from the washout period through the duration of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical cennre	Petaluma	California	United States	94954
2	Medical center	Roseburg	Oregon	United States	97471
3	Medical center	Houston	Texas	United States	77008
4	Medical center	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Oculis

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2019
• Statistical Analysis Plan - Nov 8, 2019

More Information

Publications

• Jóhannesson G, Moya-Ortega MD, Ásgrímsdóttir GM, Lund SH, Thorsteinsdóttir M, Loftsson T, Stefánsson E. Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid. Acta Ophthalmol. 2014 Sep;92(6):550-6. doi: 10.1111/aos.12334. Epub 2013 Dec 24.
• Ohira A, Hara K, Jóhannesson G, Tanito M, Ásgrímsdóttir GM, Lund SH, Loftsson T, Stefánsson E. Topical dexamethasone γ-cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema. Acta Ophthalmol. 2015 Nov;93(7):610-5. doi: 10.1111/aos.12803. Epub 2015 Jul 23.
• Saari KM, Nelimarkka L, Ahola V, Loftsson T, Stefánsson E. Comparison of topical 0.7% dexamethasone-cyclodextrin with 0.1% dexamethasone sodium phosphate for postcataract inflammation. Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):620-6. Epub 2005 Oct 11.
• Tanito M, Hara K, Takai Y, Matsuoka Y, Nishimura N, Jansook P, Loftsson T, Stefánsson E, Ohira A. Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema. Invest Ophthalmol Vis Sci. 2011 Oct 10;52(11):7944-8. doi: 10.1167/iovs.11-8178.

• Responsible Party: Oculis
• ClinicalTrials.gov Identifier: NCT04130802
• Other Study ID Numbers: DX-216
• First Posted: Oct 17, 2019
• Last Update Posted: Mar 15, 2022
• Last Verified: Jan 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 Oculis: post-cataract,; inflammation; Pain; post-surgery; corticosteroid; anterior chamber cells; flares
• Additional relevant MeSH terms: Cataract; Keratitis; Inflammation; Pain, Postoperative; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	OCS-01 1.5% mg/mL QD	OCS-01 1.5% mg/mL BID	Placebo (Vehicle) BID
Arm/Group Description	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops Placebo: Vehicle eye drops	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops	eye drops Placebo: Vehicle eye drops
Period Title: Overall Study
STARTED	51	51	51
COMPLETED	50	50	48
NOT COMPLETED	1	1	3

Baseline Characteristics

Arm/Group Title	OCS-01 1.5% mg/mL QD	OCS-01 1.5% mg/mL BID	Placebo (Vehicle) BID	Total
Arm/Group Description	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops Placebo: Vehicle eye drops	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops	eye drops Placebo: Vehicle eye drops	Total of all reporting groups
Overall Participants	51	51	51	153
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	13 25.5%	22 43.1%	15 29.4%	50 32.7%
>=65 years	38 74.5%	29 56.9%	36 70.6%	103 67.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.0 (6.86)	65.8 (6.59)	67.5 (8.41)	67.1 (7.34)
Sex: Female, Male (Count of Participants)
Female	33 64.7%	36 70.6%	32 62.7%	101 66%
Male	18 35.3%	15 29.4%	19 37.3%	52 34%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2%	0 0%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	1 2%	0 0%	1 0.7%
Black or African American	3 5.9%	8 15.7%	4 7.8%	15 9.8%
White	47 92.2%	42 82.4%	47 92.2%	136 88.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	51 100%	51 100%	51 100%	153 100%

Outcome Measures

1. Primary Outcome

Title	Anterior Chamber Cells
Description	Absence of anterior chamber cells as measured by slit beam with fluoresceine The outcome measure was the number of subjects with an absence of anterior chamber cells
Time Frame	at Day 15 (visit 6)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OCS-01 1.5% mg/mL QD	OCS-01 1.5% mg/mL BID	Placebo (Vehicle) BID
Arm/Group Description	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops	eye drops Placebo: Vehicle eye drops
Measure Participants	51	51	51
Number [Number of subjects with no cells]	26	34	10

2. Primary Outcome

Title	Ocular Pain
Description	Absence of pain as assessed by Ocular Pain Grading Scale (Min 0, Max 10) in which 0 is no pain and 10 is the worst possible. Outcome measure was the number of subjects who reported no pain
Time Frame	at Day 4 (visit 4)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OCS-01 1.5% mg/mL QD	OCS-01 1.5% mg/mL BID	Placebo (Vehicle) BID
Arm/Group Description	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops Placebo: Vehicle eye drops	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops	eye drops Placebo: Vehicle eye drops
Measure Participants	51	51	51
Number [number of subjects with no pain]	37	32	23

Adverse Events

Time Frame	The AEs were queried at visit 2 (Day 1, 18 - 30h post surgery), visit 4 (Day 4) , visit 5 (Day 8), visit 6 (Day 15) & visit 7 (Day 22)
Arm/Group Title	OCS-01 1.5% mg/mL QD		OCS-01 1.5% mg/mL BID		Placebo (Vehicle) BID
Arm/Group Description	eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops		eye drops OCS-01 - Dexamethasone Cyclodextrin Nanoparticle Ophthalmic Suspension 1.5% mg/mL: OCS-01 eye drops		eye drops Placebo: Vehicle eye drops
All Cause Mortality
	OCS-01 1.5% mg/mL QD		OCS-01 1.5% mg/mL BID		Placebo (Vehicle) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)		1/51 (2%)
Serious Adverse Events
	OCS-01 1.5% mg/mL QD		OCS-01 1.5% mg/mL BID		Placebo (Vehicle) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		1/51 (2%)		1/51 (2%)
Blood and lymphatic system disorders
Anemia	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Eye disorders
noninfectious endophthamitis	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/51 (0%)		0/51 (0%)		1/51 (2%)	1
Other (Not Including Serious) Adverse Events
	OCS-01 1.5% mg/mL QD		OCS-01 1.5% mg/mL BID		Placebo (Vehicle) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/51 (33.3%)		10/51 (19.6%)		20/51 (39.2%)
Eye disorders
conjunctival hyperaemia	3/51 (5.9%)	3	2/51 (3.9%)	2	8/51 (15.7%)	8
corneal edema	5/51 (9.8%)	5	1/51 (2%)	1	8/51 (15.7%)	8
anteror chamber inflammation	1/51 (2%)	1	3/51 (5.9%)	3	0/51 (0%)	0
iritis	3/51 (5.9%)	3	0/51 (0%)	0	2/51 (3.9%)	2
vitreous detachment	2/51 (3.9%)	2	1/51 (2%)	1	0/51 (0%)	0
foreign body sensation in eyes	1/51 (2%)	1	1/51 (2%)	1	1/51 (2%)	1
posterior capsule opacification	2/51 (3.9%)	2	0/51 (0%)	0	0/51 (0%)	0
anterior chamber flare	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
ciliary hyperaemia	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
conjunctival oedema	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
corneal disorder	1/51 (2%)	1	0/51 (0%)	0	1/51 (2%)	1
eye inflammation	1/51 (2%)	1	0/51 (0%)	0	2/51 (3.9%)	2
keratic precipitates	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
lacrimination increased	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
macular oedema	0/51 (0%)	0	1/51 (2%)	1	1/51 (2%)	1
non infectious endophtalmitis	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
retinal haemmorrhage	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
retinal pigment epitheliopathy	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
vision blurred	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
anterior chamber cell	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
eye pain	0/51 (0%)	0	0/51 (0%)	0	4/51 (7.8%)	4
photophobia	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
photopsia	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
punctate keratitis	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
pupillary disorder	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
visual acuity reduced	0/51 (0%)	0	0/51 (0%)	0	2/51 (3.9%)	2
vitreous floaters	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
vitreous detachment	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
Gastrointestinal disorders
frequent bowel movements	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
General disorders
Instillation site pain	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
instillation site foreign body sensation	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Infections and infestations
upper respiratory tract infection	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Investigations
intraocular pressure increased	0/51 (0%)	0	1/51 (2%)	1	1/51 (2%)	1
Metabolism and nutrition disorders
gout	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Musculoskeletal and connective tissue disorders
arthralgia	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
bursitis	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
Nervous system disorders
dizziness	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
dysgeusia	0/51 (0%)	0	1/51 (2%)	1	0/51 (0%)	0
headache	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
dyspnoea	1/51 (2%)	1	0/51 (0%)	0	0/51 (0%)	0
respiratory failure	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Skin and subcutaneous tissue disorders
Dandruff	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1
Vascular disorders
deep vein thrombosis	0/51 (0%)	0	0/51 (0%)	0	1/51 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator agrees not to publish/present the results until such time as the aggregate study results are published. After such time, Investigator may publish the results in accordance with the following: Investigator shall submit to Sponsor any such proposed publication/presentation resulting from or relating to the Study at least 60 days prior to the submission for publication. Sponsor may require the delay of publication/presentation for an additional period of time not to exceed 120 days.