Efficacy and Safety of Dexamethasone Nanoparticles Eye Drops in Diabetic Macular Edema

• Sponsor: Oculis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05343156
• Collaborator: (none)
• Enrollment: 144
• Location: 1
• Arms: 2
• Actual Duration (Months): 18.3
• Patients Per Site Per Month: 7.9

Study Details

Study Description

Brief Summary

Anti-inflammatory or anti-angiogenic drugs play an ever- increasing role in the treatment of diabetic macular edema (DME). The drug delivery systems, such as injections of corticosteroid and or vascular endothelial growth factor (VEGF) antibodies into the vitreous cavity or slow release drug capsules surgically implanted in the eyes run the risk of surgical complications including infections, hemorrhages and cataracts and place a huge demand on eye care resources significantly increase the risk of cardiovascular events and death.

A non-invasive drug delivery platform with steroid eye drops, reaching the back of the eye to treat DME and other retinal diseases would circumvent most of these problems.

A novel drug delivery platform is required for ocular therapy. Oculis ehf. has developed a drug delivery platform, which is based on cyclodextrin nanoparticles that dissolve in the tear fluid to form water-soluble drug/cyclodextrin complex nanoparticles. Animal and initial clinical testing has shown the potential for this technology to increase the drug concentration in the eye tissues including the retina and therefore treat retinal diseases like DME.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Dexamethasone nanoparticles eye drops	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Dexamethasone Nanoparticles Eye Drops in Diabetic Macular Edema
• Actual Study Start Date: Sep 18, 2017
• Actual Primary Completion Date: Mar 28, 2019
• Actual Study Completion Date: Mar 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DexNP Eye Drop The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks.	Drug: Dexamethasone nanoparticles eye drops; DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Placebo Comparator: Vehicle Eye Drop The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks.	Drug: Dexamethasone nanoparticles eye drops; DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) [Baseline & Week 12]

   The primary efficacy endpoint was summarized by treatment group using descriptive statistics, including 70%, 90% and 95% confidence intervals (CIs). Change from baseline to Week 12 is also summarised by treatment group. The primary analysis of the primary endpoint employed a linear model with change from baseline ETDRS BCVA letters as the response, baseline ETDRS BCVA letters as a covariate, and treatment as a main effect factor, using the ITT population and with multiple imputation pattern mixture model techniques used to impute missing data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Had DME of less than 3 years duration since diagnosis with presence of intraretinal and/or subretinal fluid in the study eye, with CMT of ≥ 310 µm by SD-OCT at baseline (Visit 2) (as measured by the Investigator).

2. Had definite retinal thickening in the study eye due to DME involving the central macula based on the Investigator's clinical evaluation and by SD-OCT;

...

Key Exclusion Criteria:

1. Had macular edema considered to be due to a cause other than DME;

2. Had a decrease in BCVA due to causes other than DME (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, previous vitreoretinal surgery, central serous retinopathy, non-retinal condition, substantial cataract, macular ischemia) that is likely to be decreasing BCVA by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).

...

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Glostrup Hospital	Glostrup		Denmark	2600

Sponsors and Collaborators

• Oculis

Investigators

• Study Director: Michael Larsen, MD, Glostrup University Hospital, Copenhagen

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 13, 2017

More Information

Publications

None provided.

• Responsible Party: Oculis
• ClinicalTrials.gov Identifier: NCT05343156
• Other Study ID Numbers: DX211
• First Posted: Apr 25, 2022
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Macular Edema; Edema; Dexamethasone; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	DexNP Eye Drop	Vehicle Eye Drop
Arm/Group Description	The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Period Title: Overall Study
STARTED	99	45
COMPLETED	91	42
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	DexNP Eye Drop	Vehicle Eye Drop	Total
Arm/Group Description	The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	Total of all reporting groups
Overall Participants	99	45	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.6 (9.5)	66.1 (9.92)	64.4 (9.67)
Sex: Female, Male (Count of Participants)
Female	35 35.4%	17 37.8%	52 36.1%
Male	64 64.6%	28 62.2%	92 63.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	98 99%	45 100%	143 99.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA)
Description	The primary efficacy endpoint was summarized by treatment group using descriptive statistics, including 70%, 90% and 95% confidence intervals (CIs). Change from baseline to Week 12 is also summarised by treatment group. The primary analysis of the primary endpoint employed a linear model with change from baseline ETDRS BCVA letters as the response, baseline ETDRS BCVA letters as a covariate, and treatment as a main effect factor, using the ITT population and with multiple imputation pattern mixture model techniques used to impute missing data.
Time Frame	Baseline & Week 12

Outcome Measure Data

Analysis Population Description

Change from baseline to week 12 in Study Eye ETDRS BCVA Letters using Multiple Imputation (Intent-to-Treat Population)

Arm/Group Title	DexNP Eye Drop	Vehicle Eye Drop
Arm/Group Description	The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks	The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Measure Participants	99	45
Least Squares Mean (70% Confidence Interval) [ETDRS BCVA Letters]	2.62	1.04

Adverse Events

Time Frame	Subjects were monitored for safety on all study visits. Assessment of AEs, including definition of seriousness, severity and causality was performed at each visit : day 1 (visit 2), week 2 (visit 3), week 4 (visit 4), week 8 (visit 5) , week 12 (visit 6) and week 16 (visit 7)
Arm/Group Title	DexNP Eye Drop		Vehicle Eye Drop
Arm/Group Description	The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks		The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks. Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
All Cause Mortality
	DexNP Eye Drop		Vehicle Eye Drop
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/99 (2%)		0/45 (0%)
Serious Adverse Events
	DexNP Eye Drop		Vehicle Eye Drop
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/99 (11.1%)		1/45 (2.2%)
Cardiac disorders
Atrial fibrillation	2/99 (2%)	2	0/45 (0%)	0
Cardiac failure	2/99 (2%)	2	0/45 (0%)	0
Myocardial infarction	0/99 (0%)	0	1/45 (2.2%)	1
Endocrine disorders
Type 2 diabetes mellitus	1/99 (1%)	2	0/45 (0%)	0
diabetic ulcer	1/99 (1%)	1	0/45 (0%)	0
Eye disorders
Retinal detachment	1/99 (1%)	1	0/45 (0%)	0
General disorders
Death	1/99 (1%)	1	0/45 (0%)	0
Sudden cardiac death	1/99 (1%)	1	0/45 (0%)	0
Infections and infestations
Influenza	1/99 (1%)	1	0/45 (0%)	0
Urinary tract infection	1/99 (1%)	1	0/45 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/99 (1%)	1	0/45 (0%)	0
Vascular disorders
Peripheral arterial occlusive disease	1/99 (1%)	1	0/45 (0%)	0
Other (Not Including Serious) Adverse Events
	DexNP Eye Drop		Vehicle Eye Drop
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/99 (32.3%)		9/45 (20%)
Eye disorders
Eye irritation	3/99 (3%)	3	0/45 (0%)	0
Ocular hypertension	3/99 (3%)	3	0/45 (0%)	0
Cataract subcapscular	1/99 (1%)	1	1/45 (2.2%)	1
conjunctival hemorrhage	1/99 (1%)	1	0/45 (0%)	0
Diabetic retinal edema	1/99 (1%)	1	0/45 (0%)	0
erythema of eyelid	1/99 (1%)	1	1/45 (2.2%)	1
eyelid ptosis	1/99 (1%)	1	0/45 (0%)	0
glaucoma	1/99 (1%)	1	0/45 (0%)	0
noninfective conjunctivitis	1/99 (1%)	1	0/45 (0%)	0
Ocular hyperemia	1/99 (1%)	1	1/45 (2.2%)	1
photophobia	1/99 (1%)	1	0/45 (0%)	0
posterior capsule opacification	1/99 (1%)	1	1/45 (2.2%)	1
conjunctival hyperemia	0/99 (0%)	0	1/45 (2.2%)	1
conjunctivitis	0/99 (0%)	0	1/45 (2.2%)	1
corneal edema	0/99 (0%)	0	1/45 (2.2%)	1
eye infection bacterial	0/99 (0%)	0	1/45 (2.2%)	1
eye pruritus	0/99 (0%)	0	1/45 (2.2%)	1
foreign body sensation in eyes	0/99 (0%)	0	1/45 (2.2%)	1
keratopathy	0/99 (0%)	0	1/45 (2.2%)	1
retinal pigment epitheliopathy	0/99 (0%)	0	1/45 (2.2%)	1
Infections and infestations
conjunctivitis	0/99 (0%)	0	1/45 (2.2%)	1
eye infection bacterial	0/99 (0%)	0	1/45 (2.2%)	1
Investigations
Intraocular pressure increased	21/99 (21.2%)	23	0/45 (0%)	0
Blood glucose fluctuation	1/99 (1%)	1	0/45 (0%)	0
Nervous system disorders
dysgeusia	2/99 (2%)	2	0/45 (0%)	0
Psychiatric disorders
insomnia	1/99 (1%)	1	0/45 (0%)	0
Respiratory, thoracic and mediastinal disorders
dyspnea	1/99 (1%)	1	0/45 (0%)	0

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.