COBALT: A Safety and Efficacy Study of OZURDEX® in Macular Edema Associated With Branch Retinal Vein Occlusion

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01903720
• Collaborator: (none)
• Enrollment: 71
• Location: 1
• Arm: 1
• Actual Duration (Months): 20.4
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of OZURDEX® (700 µg dexamethasone implant) in patients with macular edema associated with branch retinal vein occlusion.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema; Retinal Vein Occlusion	Drug: dexamethasone implant	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Jul 16, 2013
• Actual Primary Completion Date: Sep 24, 2014
• Actual Study Completion Date: Mar 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OZURDEX® OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.	Drug: dexamethasone implant; OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.; Other Names: OZURDEX®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 6 [Baseline, Month 6]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read correctly means that the vision improved and a negative number change in the number of letters read correctly means that the vision has worsened.

Secondary Outcome Measures

1. Change From Baseline in Central Retinal Thickness (CRT) at Month 6 [Baseline, Month 6]

   CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.

2. Change From Baseline in BCVA at Month 12 [Baseline, Month 12]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read correctly means that the vision improved and a negative number change in the number of letters read correctly means that the vision has worsened.

3. Change From Baseline in CRT at Month 12 [Baseline, Month 12]

   CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.

4. Change From Baseline in BCVA at Each Visit [Baseline, Week 1, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read means that the vision improved and a negative number change in the number of letters read means that the vision has worsened.

5. Change From Baseline in CRT at Each Visit [Baseline, Week 1, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12]

   CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.

6. Percentage of Participants With a Change From Baseline of 15 or More Letters in BCVA [Baseline, Months 6 and 12]

   BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). An increase in the number of letters read correctly means that the vision improved and a decrease in the number of letters read correctly means that the vision has worsened.

7. Percentage of Participants Receiving a Second Injection [12 Months]

8. Percentage of Participants Receiving a Third Injection [12 Months]

9. Time to Second Injection [12 Months]

   Time in weeks from the first injection to the second injection.

10. Time to Third Injection [12 Months]

    Time in weeks from the second injection to the third injection.

11. Percentage of Participants Who Received Laser Treatments [12 Months]

    Participants underwent laser photocoagulation therapy for all areas of foveal leakage and non-perfusion, as well as areas of extensive retinal hyperplasia if applicable for rescue therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of macular edema

• Best corrected visual acuity of approximately 20/400 to 20/40 in the study eye

Exclusion Criteria:

• Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) within 1 month

• Intraocular surgery, including cataract surgery, and/or laser surgery of any type within 3 months

• Any active ocular infection in either eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Seoul		Korea, Republic of

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Yoon YH, Kim JW, Lee JY, Kim IT, Kang SW, Yu HG, Koh HJ, Kim SS, Chang DJ, Simonyi S. Dexamethasone Intravitreal Implant for Early Treatment and Retreatment of Macular Edema Related to Branch Retinal Vein Occlusion: The Multicenter COBALT Study. Ophthalmologica. 2018;240(2):81-89. doi: 10.1159/000487547. Epub 2018 Apr 11.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01903720
• Other Study ID Numbers: APMA-OZU-01-01
• First Posted: Jul 19, 2013
• Last Update Posted: Apr 17, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Dexamethasone

Study Results

Participant Flow

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Period Title: Overall Study
STARTED	71
COMPLETED	59
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Overall Participants	71
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.46 (9.19)
Age, Customized (participants) [Number]
30 to 39 years	1 1.4%
40 to 49 years	12 16.9%
50 to 59 years	29 40.8%
60 to 69 years	22 31%
70 years and over	7 9.9%
Sex: Female, Male (Count of Participants)
Female	33 46.5%
Male	38 53.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 6
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read correctly means that the vision improved and a negative number change in the number of letters read correctly means that the vision has worsened.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all enrolled participants. "n" in the category is the number of participants with data available for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	51.90 (13.55)
Change from Baseline at Month 6 (n=62)	18.60 (12.90)

2. Secondary Outcome

Title	Change From Baseline in Central Retinal Thickness (CRT) at Month 6
Description	CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	505.13 (129.91)
Change from Baseline at Month 6 (n=62)	-246.82 (150.74)

3. Secondary Outcome

Title	Change From Baseline in BCVA at Month 12
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read correctly means that the vision improved and a negative number change in the number of letters read correctly means that the vision has worsened.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	51.90 (13.55)
Change from Baseline at Month 12 (n=59)	15.27 (14.99)

4. Secondary Outcome

Title	Change From Baseline in CRT at Month 12
Description	CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	505.13 (129.91)
Change from Baseline at Month 12 (n=59)	-196.90 (164.07)

5. Secondary Outcome

Title	Change From Baseline in BCVA at Each Visit
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). A positive number change in the number of letters read means that the vision improved and a negative number change in the number of letters read means that the vision has worsened.
Time Frame	Baseline, Week 1, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available at the given time-point for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	51.90 (13.55)
Change from Baseline at Week 1 (n=70)	12.80 (10.69)
Change from Baseline at Month 1 (n=66)	16.08 (10.75)
Change from Baseline at Month 2 (n=62)	18.84 (12.16)
Change from Baseline at Month 3 (n=63)	17.59 (12.90)
Change from Baseline at Month 4 (n=59)	14.37 (13.47)
Change from Baseline at Month 5 (n=63)	18.10 (13.44)
Change from Baseline at Month 6 (n=62)	18.60 (12.90)
Change from Baseline at Month 7 (n=60)	18.02 (12.64)
Change from Baseline at Month 8 (n=61)	16.02 (13.39)
Change from Baseline at Month 9 (n=59)	15.88 (13.35)
Change from Baseline at Month 10 (n=60)	17.68 (13.17)
Change from Baseline at Month 11 (n=59)	15.54 (14.04)
Change from Baseline at Month 12 (n=59)	15.27 (14.99)

6. Secondary Outcome

Title	Change From Baseline in CRT at Each Visit
Description	CRT was measured in the study eye using optical computed tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina. A negative change from Baseline indicates an improvement.
Time Frame	Baseline, Week 1, Months 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available at the given time-point for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Baseline	505.13 (129.91)
Change from Baseline at Week 1 (n=70)	-173.67 (140.57)
Change from Baseline at Month 1 (n=66)	-229.48 (142.45)
Change from Baseline at Month 2 (n=62)	-255.55 (139.01)
Change from Baseline at Month 3 (n=63)	-188.17 (179.84)
Change from Baseline at Month 4 (n=59)	-100.76 (150.97)
Change from Baseline at Month 5 (n=63)	-202.41 (157.66)
Change from Baseline at Month 6 (n=62)	-246.82 (150.74)
Change from Baseline at Month 7 (n=60)	-220.13 (143.07)
Change from Baseline at Month 8 (n=60)	-175.83 (133.93)
Change from Baseline at Month 9 (n=59)	-211.46 (158.10)
Change from Baseline at Month 10 (n=59)	-250.97 (133.24)
Change from Baseline at Month 11 (n=59)	-219.14 (144.47)
Change from Baseline at Month 12 (n=59)	-196.90 (164.07)

7. Secondary Outcome

Title	Percentage of Participants With a Change From Baseline of 15 or More Letters in BCVA
Description	BCVA is measured in the study eye using an eye chart and is reported as the number of letters read correctly ranging from 0 (worst) to 100 letters (best). An increase in the number of letters read correctly means that the vision improved and a decrease in the number of letters read correctly means that the vision has worsened.
Time Frame	Baseline, Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants. "n" in the category is the number of participants with data available at the given time-point for analysis.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	62
Month 6_Increase	64.52 90.9%
Month 6_Decrease	1.61 2.3%
Month 12_Increase (n=59)	55.93 78.8%
Month 12_Decrease (n=59)	5.08 7.2%

8. Secondary Outcome

Title	Percentage of Participants Receiving a Second Injection
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Number [percentage of participants]	18.31 25.8%

9. Secondary Outcome

Title	Percentage of Participants Receiving a Third Injection
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Number [percentage of participants]	49.30 69.4%

10. Secondary Outcome

Title	Time to Second Injection
Description	Time in weeks from the first injection to the second injection.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Mean (Standard Deviation) [weeks]	20.78 (6.02)

11. Secondary Outcome

Title	Time to Third Injection
Description	Time in weeks from the second injection to the third injection.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Mean (Standard Deviation) [weeks]	19.20 (3.09)

12. Secondary Outcome

Title	Percentage of Participants Who Received Laser Treatments
Description	Participants underwent laser photocoagulation therapy for all areas of foveal leakage and non-perfusion, as well as areas of extensive retinal hyperplasia if applicable for rescue therapy.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
Measure Participants	71
Number [percentage of participants]	0.0 0%

Adverse Events

Arm/Group Title	OZURDEX®
Arm/Group Description	OZURDEX® (700 µg dexamethasone implant) administered intravitreally on day 0, and approximately every 4 months as needed (based on physician judgment) for up to 12 months.
All Cause Mortality
	OZURDEX®
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	OZURDEX®
	Affected / at Risk (%)	# Events
Total	2/71 (2.8%)
Eye disorders
Cataract	1/71 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer	1/71 (1.4%)
Other (Not Including Serious) Adverse Events
	OZURDEX®
	Affected / at Risk (%)	# Events
Total	44/71 (62%)
Eye disorders
Dry eye	14/71 (19.7%)
Cataract	12/71 (16.9%)
Conjunctival haemorrhage	8/71 (11.3%)
Vitreous detachment	4/71 (5.6%)
Investigations
Intraocular pressure increased	25/71 (35.2%)
Nervous system disorders
Headache	5/71 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.