Study Assessing AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03739593
• Collaborator: (none)
• Enrollment: 49
• Locations: 11
• Arms: 2
• Actual Duration (Months): 15.9
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability and efficacy of AR-1105 (dexamethasone implant) for the treatment of macular edema (ME) due to retinal vein occlusion (RVO). A more durable intravitreal implant containing a low dose of dexamethasone may result in less frequent retreatments, and potentially lower the incidence of steroid-related side effects without compromising efficacy.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema	Drug: AR-1105-CF1; Drug: AR-1105-CF2	Phase 2

Detailed Description

AR-1105 is a dexamethasone containing implant drug delivery system that is injected into the back of the eye. It is designed to dissolve slowly over time, continuously releasing a consistent low dose of steroid to treat the symptoms of RVO and associated inflammation with a goal of halting further visual disturbance and damage, and also possibly restoring some vision as symptoms are controlled. In this study, 2 different formulations are being tested to find the optimum combination of efficacy, safety and durability that will offer patients a potential treatment option that is as safe and effective as the treatments currently available, but which requires less frequent injections and potentially has a lower risk for certain side-effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single injection of either of 2 formulations of AR-1105 dexamethasone intravitreal implant (CF1 or CF2) administered in a single eye. An initial safety cohort of up-to 5 subjects may be enrolled onto CF1 prior to the randomized phase. During the randomized phase of the study, subjects will be assigned in a 1:1 ratio to either CF1 or CF2. Each subject will complete a 6-month primary evaluation period. Residual implant assessment will be performed by 3-field fundus photography at Day 7 and at Months 3, 4, 5, and 6, and if necessary at monthly visits thereafter until the subject requires retreatment, or until 1 month after the implant is no longer visible, or to Month 9, whichever comes first.Single injection of either of 2 formulations of AR-1105 dexamethasone intravitreal implant (CF1 or CF2) administered in a single eye. An initial safety cohort of up-to 5 subjects may be enrolled onto CF1 prior to the randomized phase. During the randomized phase of the study, subjects will be assigned in a 1:1 ratio to either CF1 or CF2. Each subject will complete a 6-month primary evaluation period. Residual implant assessment will be performed by 3-field fundus photography at Day 7 and at Months 3, 4, 5, and 6, and if necessary at monthly visits thereafter until the subject requires retreatment, or until 1 month after the implant is no longer visible, or to Month 9, whichever comes first.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Safety and Proof-of-concept Study to Assess Safety, Tolerability and Efficacy of AR-1105 in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)
• Actual Study Start Date: Mar 13, 2019
• Actual Primary Completion Date: May 14, 2020
• Actual Study Completion Date: Jul 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AR-1105-CF1 Single dose of AR-1105-CF1 (dexamethasone, targeted dose of 340 mcg) administered as an intravitreal implant into a single eye of up to 20 subjects who will be followed for 6 months	Drug: AR-1105-CF1; AR-1105 clinical formulation 1 (AR-1105-CF1); Other Names: AR-1105-CF1 (dexamethasone intravitreal implant)
Experimental: AR-1105-CF2 Single dose of AR-1105-CF2 (dexamethasone, targeted dose of 340 mcg) administered as an intravitreal implant into a single eye of up to 20 subjects who will be followed for 6 months	Drug: AR-1105-CF2; AR-1105 clinical formulation 2 (AR-1105-CF2); Other Names: AR-1105-CF2 (dexamethasone intravitreal implant)

Outcome Measures

Primary Outcome Measures

1. Safety Tolerability: Number of Ocular and Non-ocular TEAEs [Up to 6 months treatment duration]

   Treatment-emergent adverse events summarized at the subject level by system organ class and preferred term are available in the Adverse Events module. Data reported in the table below corresponds to the total number of participants with ocular and non-ocular treatment-emergent adverse events (TEAEs).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. At least 18 years of age

2. Vision loss due to clinically detectable macular edema (ME) associated with either central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Subjects may be treatment-naïve, or if previously-treated with a steroid, must have demonstrated response to treatment

3. Duration of macular edema (ME) ≥9 months in subjects with CRVO and ≥12 months in subjects with BRVO. If both eyes are eligible, the study eye will be the eye with worse VA

4. Best-corrected visual acuity (BCVA) as measured by the early treatment of diabetic retinopathy study (ETDRS) methodology of between 25 and 70 letters, in the study eye and better than 35 letters, in the non-study eye

5. Retinal thickness in the central subfield of >290 µm (females) and >305 μm (males) if using a Cirrus (Zeiss) instrument, or if a Spectralis (Heidelberg) instrument is used, thickness should be >305 μm (females) or >320 μm (males) in the study eye

6. Be able to understand and willing to provide written informed consent.

7. Be willing and able to adhere to the instructions set forth in the study protocol

Exclusion Criteria:

Ophthalmic:

1. Presence of a clinically significant epiretinal membrane, active retinal or optic disc neovascularization, active or history of choroidal neovascularization, presence of rubeosis iridis

2. History or presence of herpetic infection, toxoplasmosis, chorioretinopathy.

3. Subjects with moderate non-proliferative diabetic retinopathy or worse in either eye are excluded from participation

4. Any active infection

5. Aphakia, significant posterior capsule tear or iris trauma in the study eye

6. Anterior-chamber intraocular lens

7. Clinically significant media opacity

8. History of glaucoma or visual field loss

9. Ocular hypertension in the study eye at qualification, (with or without treatment)

10. History of corticosteroid-induced IOP increase in either eye

11. Ocular condition in the study eye that, in the opinion of the investigator, would prevent a 15-letter improvement in visual acuity

12. Received an intraocular steroid injection or implant within 6 months or any anti-VEGF treatment within 2 months prior to screening. Prior treatment with RETISERT® or ILUVIEN® or pan-retinal photocoagulation (PRP) is exclusionary

13. Intraocular surgery (including laser refractive or eyelid surgery) within 3 months prior to Visit 1 or anticipated need for ocular surgery or ophthalmic laser treatment during the study treatment period

14. Currently using topical corticosteroids in the vicinity of the eyes within the 1 month prior to Visit 1

15. Periocular depot of steroids placed within 6 months prior to qualification

16. Ocular medications that are specifically disallowed in this protocol for any condition during the study or within the specified timeframe prior to Visit 2

17. Have progressive optic nerve disease or retinal disease other than retinopathy due to RVO that affects BCVA

Systemic:

1. Currently using or anticipating the use of systemic corticosteroids during the study (with the exception of inhaled, intranasal or topical corticosteroids)

2. Any clinically significant or uncontrolled serious or severe medical or psychiatric condition

3. Participation in any other interventional clinical study within 30 days prior to Visit 1

4. History of hypersensitivity or poor tolerance to any components of the preparations to be used in this study such as dexamethasone or biodegradable polymer (PLGA) excipients or fluorescein

5. Systemic condition that may confound the study outcome per the investigator's opinion

6. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Research Institute, LLC	Phoenix	Arizona	United States	85053
2	Retina Vitreous Associates	Beverly Hills	California	United States	90211
3	Byers Eye Institute at Stanford	Palo Alto	California	United States	94303
4	Florida Eye Clinic	Altamonte Springs	Florida	United States	32701
5	Center for Retina & Macular Disease	Lakeland	Florida	United States	33805
6	Retina Specialty Institute	Pensacola	Florida	United States	32503
7	Mid-Atlantic Retina	Cherry Hill	New Jersey	United States	08034
8	Cleveland Clinic- Cole Eye Institute	Cleveland	Ohio	United States	44195
9	Retina Research Institute of Texas	Abilene	Texas	United States	79606
10	Texas Retina Associates	Arlington	Texas	United States	76012
11	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240

Sponsors and Collaborators

• Aerie Pharmaceuticals

Investigators

• Study Director: Susan Rowan, Aerie Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Jan 22, 2019
• Statistical Analysis Plan - Jun 10, 2020

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03739593
• Other Study ID Numbers: AR-1105-CS201
• First Posted: Nov 14, 2018
• Last Update Posted: Feb 28, 2022
• Last Verified: Feb 1, 2022

• 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 Aerie Pharmaceuticals: Macular Edema; Retinal Vein Occlusion; Dexamethasone Intravitreal Implant
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Dexamethasone; Dexamethasone acetate; BB 1101

Study Results

Participant Flow

Arm/Group Title	Initial Phase: AR-1105-CF1	Randomization Phase: AR-1105-CF1	Randomization Phase: AR-1105-CF2
Arm/Group Description	Single dose of AR- 1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye	Single dose of AR- 1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye	Single dose of AR- 1105-clinical formulation 2 (CF2) dexamethasone 340 mcg administered as an intravitreal implant into a single eye
Period Title: Overall Study
STARTED	5	22	22
COMPLETED	2	16	14
NOT COMPLETED	3	6	8

Baseline Characteristics

Arm/Group Title	AR-1105-CF1 Initial Phase	AR-1105-CF1 Randomization Phase	AR-1105-CF2 Randomization Phase	Total
Arm/Group Description	Single dose of AR-1105-CF1 (dexamethasone 340 mcg) administered as an intravitreal implant into a single eye	Single dose of AR-1105-CF1 (dexamethasone 340 mcg) administered as an intravitreal implant into a single eye	Single dose of AR-1105-CF2 (dexamethasone, 340 mcg) administered as an intravitreal implant into a single eye	Total of all reporting groups
Overall Participants	5	22	22	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 40%	10 45.5%	6 27.3%	18 36.7%
>=65 years	3 60%	12 54.5%	16 72.7%	31 63.3%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	67	66	72	68
Sex: Female, Male (Count of Participants)
Female	0 0%	9 40.9%	13 59.1%	22 44.9%
Male	5 100%	13 59.1%	9 40.9%	27 55.1%
Race/Ethnicity, Customized (Count of Participants)
Race : American Indian or Alaska Native	0 0%	1 4.5%	0 0%	1 2%
Race : Asian	0 0%	0 0%	2 9.1%	2 4.1%
Race : Black or African American	0 0%	2 9.1%	1 4.5%	3 6.1%
Race : Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Race : White	5 100%	19 86.4%	19 86.4%	43 87.8%
Race : Other	0 0%	0 0%	0 0%	0 0%
Race : Multiple Race	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	22 100%	22 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Safety Tolerability: Number of Ocular and Non-ocular TEAEs
Description	Treatment-emergent adverse events summarized at the subject level by system organ class and preferred term are available in the Adverse Events module. Data reported in the table below corresponds to the total number of participants with ocular and non-ocular treatment-emergent adverse events (TEAEs).
Time Frame	Up to 6 months treatment duration

Outcome Measure Data

Analysis Population Description

All safety evaluations were conducted on subjects in the safety population. The safety population included all subjects who received study medication. This population was used to summarize safety variables. Subjects were analyzed as-treated

Arm/Group Title	Initial Phase: AR-1105-CF1	Randomization Phase: AR-1105-CF1	Randomization Phase: AR-1105-CF2
Arm/Group Description	Single dose of AR-1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye	Single dose of AR-1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye	Single dose of AR-1105-clinical formulation 2 (CF2) dexamethasone 340 mcg administered as an intravitreal implant into a single eye
Measure Participants	5	22	22
Number [participants]	5 100%	22 100%	22 100%

Adverse Events

Time Frame	Adverse events were documented from the time the subject signed the informed consent until Month 6 + 30 days, or up to Month 9 + 30 days in subjects with visible residual implant observed at Month 6 or beyond.
Arm/Group Title	Initial Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF2
Arm/Group Description	Single dose of AR- 1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye		Single dose of AR- 1105-clinical formulation 1 (CF1) dexamethasone 340 mcg administered as an intravitreal implant into a single eye		Single dose of AR- 1105-clinical formulation 1 (CF2) dexamethasone 340 mcg administered as an intravitreal implant into a single eye
All Cause Mortality
	Initial Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Initial Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		2/22 (9.1%)		4/22 (18.2%)
Cardiac disorders
Angina Pectoris	0/5 (0%)		0/22 (0%)		1/22 (4.5%)
Eye disorders
Visual Acuity Reduced	1/5 (20%)		1/22 (4.5%)		2/22 (9.1%)
Iris Neovascularization	1/5 (20%)		0/22 (0%)		0/22 (0%)
Cataract	0/5 (0%)		0/22 (0%)		1/22 (4.5%)
Visual Impairment	0/5 (0%)		1/22 (4.5%)		0/22 (0%)
Infections and infestations
Pneumonia	0/5 (0%)		0/22 (0%)		1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	Initial Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF1		Randomization Phase: AR-1105-CF2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		9/22 (40.9%)		11/22 (50%)
Eye disorders
Visual Acuity Reduced	1/5 (20%)		2/22 (9.1%)		3/22 (13.6%)
Macular Edema	2/5 (40%)		4/22 (18.2%)		2/22 (9.1%)
Conjunctival Haemorrhage	2/5 (40%)		2/22 (9.1%)		1/22 (4.5%)
Ocular Hypertension	0/5 (0%)		0/22 (0%)		3/22 (13.6%)
Vitreous Haemorrhage	0/5 (0%)		0/22 (0%)		3/22 (13.6%)
Vitreous Floaters	0/5 (0%)		0/22 (0%)		2/22 (9.1%)
Vision Blurred	1/5 (20%)		0/22 (0%)		0/22 (0%)
Infections and infestations
Nasopharyngitis	0/5 (0%)		2/22 (9.1%)		0/22 (0%)
Investigations
Intraocular Pressure Increased	1/5 (20%)		1/22 (4.5%)		3/22 (13.6%)
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus	1/5 (20%)		0/22 (0%)		0/22 (0%)
Product Issues
Device Malfunction	1/5 (20%)		0/22 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.