Safety and Efficacy Study of Ozurdex® Compared to Lucentis® in Patients With Branch Retinal Vein Occlusion

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01427751
• Collaborator: (none)
• Enrollment: 307
• Locations: 6
• Arms: 2
• Actual Duration (Months): 36.8
• Patients Per Site: 51.2
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex®) compared to ranibizumab (Lucentis®) in patients with branch retinal vein occlusion (BRVO).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Oct 11, 2011
• Actual Primary Completion Date: Nov 4, 2014
• Actual Study Completion Date: Nov 4, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ozurdex® Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Patients may receive up to one additional treatment, thereafter.	Drug: dexamethasone intravitreal implant; Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Patients may receive up to one additional treatment, thereafter.; Other Names: Ozurdex®
Active Comparator: Lucentis® Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Patients will receive additional treatment thereafter based on re-treatment criteria.	Biological: ranibizumab; Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Patients will receive additional treatment thereafter based on re-treatment criteria.; Other Names: Lucentis®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best Corrected Visual Acuity (BCVA) [Baseline, Month 12]

   BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the number of letters read correctly, the better the vision (or visual acuity) A positive change from Baseline (more letters read correctly) indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in Central Retinal Subfield Thickness Using Optical Coherence Tomography (OCT) [Baseline, Month 12]

   Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Month 12. A negative change from Baseline indicates improvement.

2. Percentage of Patients With 15-or-More Letter Improvement in BCVA [Baseline, Month 12]

   BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the number of letters read correctly, the better the vision (or visual acuity). An improvement in the number of letters read means that the vision has improved.

3. Percentage of Patients With a 15-or-More Letter Decrease in BCVA [Baseline, Month 12]

   BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).

4. Time to BCVA Improvement of 15-or-More Letters [12 Months]

   BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The time in days to BCVA improvement of 15-or-More letters.

5. Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (VFQ-25) [Baseline, Month 12]

   The VFQ-25 includes 25 vision-targeted questions plus one general health question which assess visual impairment on functioning and specific aspects of health-related quality of life for a total possible composite score of 0 (worst) to 100 (best functionality). A positive change from Baseline indicates improvement.

6. Percentage of Participants Not Completing the Month 12 Visit Due to Treatment Failure [12 Months]

   Treatment failure was defined as withdrawal of the participant from treatment or from the study by the investigator before the final visit because of a lack of efficacy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of branch retinal vein occlusion in at least one eye

• Visual acuity between 20/400 to 20/40

Exclusion Criteria:

• Active eye infection

• Ocular hypertension which is not controlled on monotherapy (one medication)

• Anticipated need for eye surgery during the study

• Cataract surgery in either eye within 3 months

• Eye surgery including laser of any type within 6 months

• Anti-VEGF treatment in either eye (eg, Lucentis®) within 3 months or systemic anti-VEGF treatment (eg, Avastin) within 6 months

• Use of ocular steroids within 3 months

• Use of steroids (except for inhaled or intranasal) within 1 month or anticipated use during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Paris		France
2		Munich		Germany
3		Tel Aviv		Israel
4		Milan		Italy
5		Madrid		Spain
6		London		United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bandello F, Augustin A, Tufail A, Leaback R. A 12-month, multicenter, parallel group comparison of dexamethasone intravitreal implant versus ranibizumab in branch retinal vein occlusion. Eur J Ophthalmol. 2018 Nov;28(6):697-705. doi: 10.1177/1120672117750058. Epub 2018 Apr 9.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01427751
• Other Study ID Numbers: MAF-AGN-OPH-RET-004; 2010-023900-29
• First Posted: Sep 2, 2011
• Last Update Posted: Apr 18, 2019
• Last Verified: Apr 1, 2019

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

Study Results

Participant Flow

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Period Title: Overall Study
STARTED	154	153
COMPLETED	112	139
NOT COMPLETED	42	14

Baseline Characteristics

Arm/Group Title	Ozurdex®	Lucentis®	Total
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.	Total of all reporting groups
Overall Participants	154	153	307
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (10.58)	65.5 (12.04)	67.0 (11.41)
Sex: Female, Male (Count of Participants)
Female	62 40.3%	66 43.1%	128 41.7%
Male	92 59.7%	87 56.9%	179 58.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA)
Description	BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the number of letters read correctly, the better the vision (or visual acuity) A positive change from Baseline (more letters read correctly) indicates improvement.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Baseline (n=153,153)	56.6 (10.89)	59.2 (10.92)
Change from Baseline at Month 12 (n=153,151)	7.9 (14.42)	16.9 (12.08)

2. Secondary Outcome

Title	Change From Baseline in Central Retinal Subfield Thickness Using Optical Coherence Tomography (OCT)
Description	Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Month 12. A negative change from Baseline indicates improvement.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Baseline (n=149, 149)	553.2 (170.15)	561.0 (188.93)
Change from Baseline at Month 12 (n=140,144)	-219.2 (180.51)	-253.5 (197.08)

3. Secondary Outcome

Title	Percentage of Patients With 15-or-More Letter Improvement in BCVA
Description	BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the number of letters read correctly, the better the vision (or visual acuity). An improvement in the number of letters read means that the vision has improved.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Number [percentage of participants]	33.8 21.9%	59.5 38.9%

4. Secondary Outcome

Title	Percentage of Patients With a 15-or-More Letter Decrease in BCVA
Description	BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Number [percentage of participants]	9.1 5.9%	0.7 0.5%

5. Secondary Outcome

Title	Time to BCVA Improvement of 15-or-More Letters
Description	BCVA was measured in the study eye using an eye chart and was recorded as the number of letters read correctly for a total possible score of 0 to 100. The time in days to BCVA improvement of 15-or-More letters.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Mean (Standard Deviation) [days]	73.7 (79.68)	82.0 (93.78)

6. Secondary Outcome

Title	Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (VFQ-25)
Description	The VFQ-25 includes 25 vision-targeted questions plus one general health question which assess visual impairment on functioning and specific aspects of health-related quality of life for a total possible composite score of 0 (worst) to 100 (best functionality). A positive change from Baseline indicates improvement.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population, all randomized participants, with data available for analysis.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Baseline (n=143,139)	78.1 (16.58)	80.7 (14.34)
Change from Baseline at Month 12 (n=143, 139)	3.5 (12.21)	6.6 (13.45)

7. Secondary Outcome

Title	Percentage of Participants Not Completing the Month 12 Visit Due to Treatment Failure
Description	Treatment failure was defined as withdrawal of the participant from treatment or from the study by the investigator before the final visit because of a lack of efficacy.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized participants.

Arm/Group Title	Ozurdex®	Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.	Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
Measure Participants	154	153
Number [percentage of participants]	4.5 2.9%	0.7 0.5%

Adverse Events

Time Frame	Up to 60 Weeks
Adverse Event Reporting Description	Safety population, all randomized participants who received at least 1 dose of study drug, was used to determine the number of participants at risk for Serious Adverse Events and Adverse Events.
Arm/Group Title	Ozurdex®		Lucentis®
Arm/Group Description	Injection of Ozurdex® (dexamethasone intravitreal implant) into the study eye on Day 1 and Month 5. Participants may receive up to one additional treatment, thereafter.		Injection of Lucentis® (ranibizumab) into the study eye on Day 1 and monthly for five months. Participants will receive additional treatment thereafter based on re-treatment criteria.
All Cause Mortality
	Ozurdex®		Lucentis®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ozurdex®		Lucentis®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/153 (7.8%)		16/150 (10.7%)
Cardiac disorders
Acute coronary syndrome	1/153 (0.7%)		0/150 (0%)
Atrial fibrillation	1/153 (0.7%)		0/150 (0%)
Bradyarrhythmia	1/153 (0.7%)		0/150 (0%)
Angina pectoris	0/153 (0%)		1/150 (0.7%)
Myocardial infarction	0/153 (0%)		1/150 (0.7%)
Myocardial ischaemia	0/153 (0%)		1/150 (0.7%)
Palpitations	0/153 (0%)		1/150 (0.7%)
Ear and labyrinth disorders
Vertigo	0/153 (0%)		1/150 (0.7%)
Eye disorders
Ocular hypertension	1/153 (0.7%)		0/150 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/153 (0.7%)		0/150 (0%)
Diverticulum intestinal	0/153 (0%)		1/150 (0.7%)
Gastric ulcer	0/153 (0%)		1/150 (0.7%)
Haematemesis	0/153 (0%)		1/150 (0.7%)
General disorders
Chest pain	1/153 (0.7%)		0/150 (0%)
Catheter site related reaction	0/153 (0%)		1/150 (0.7%)
Infections and infestations
Pneumonia	1/153 (0.7%)		0/150 (0%)
Endophthalmitis	0/153 (0%)		1/150 (0.7%)
Injury, poisoning and procedural complications
Hip fracture	1/153 (0.7%)		1/150 (0.7%)
Craniocerebral injury	0/153 (0%)		1/150 (0.7%)
Post procedural complication	0/153 (0%)		1/150 (0.7%)
Subdural haemorrhage	0/153 (0%)		1/150 (0.7%)
Metabolism and nutrition disorders
Dehydration	0/153 (0%)		1/150 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/153 (0.7%)		0/150 (0%)
Musculoskeletal pain	0/153 (0%)		1/150 (0.7%)
Osteoarthritis	0/153 (0%)		1/150 (0.7%)
Spinal column stenosis	0/153 (0%)		1/150 (0.7%)
Nervous system disorders
Cerebrovascular accident	1/153 (0.7%)		0/150 (0%)
Transient ischaemic attack	1/153 (0.7%)		0/150 (0%)
Subarachnoid haemorrhage	0/153 (0%)		1/150 (0.7%)
Psychiatric disorders
Agitated depression	1/153 (0.7%)		0/150 (0%)
Confusional state	1/153 (0.7%)		0/150 (0%)
Anxiety	0/153 (0%)		1/150 (0.7%)
Renal and urinary disorders
Renal failure chronic	1/153 (0.7%)		0/150 (0%)
Renal failure	0/153 (0%)		1/150 (0.7%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/153 (0.7%)		0/150 (0%)
Respiratory distress	1/153 (0.7%)		0/150 (0%)
Vascular disorders
Thrombophlebitis superficial	1/153 (0.7%)		0/150 (0%)
Other (Not Including Serious) Adverse Events
	Ozurdex®		Lucentis®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	127/153 (83%)		104/150 (69.3%)
Eye disorders
Conjunctival haemorrhage	28/153 (18.3%)		17/150 (11.3%)
Macular oedema	20/153 (13.1%)		4/150 (2.7%)
Visual acuity reduced	18/153 (11.8%)		3/150 (2%)
Cataract	13/153 (8.5%)		2/150 (1.3%)
Lenticular opacities	10/153 (6.5%)		0/150 (0%)
Ocular hypertension	9/153 (5.9%)		1/150 (0.7%)
Blepharitis	9/153 (5.9%)		3/150 (2%)
Dry eye	9/153 (5.9%)		7/150 (4.7%)
Vitreous floaters	9/153 (5.9%)		9/150 (6%)
Eye pain	6/153 (3.9%)		9/150 (6%)
Conjunctivitis	6/153 (3.9%)		9/150 (6%)
Infections and infestations
Nasopharyngitis	8/153 (5.2%)		5/150 (3.3%)
Investigations
Intraocular pressure increased	50/153 (32.7%)		16/150 (10.7%)
Nervous system disorders
Headache	4/153 (2.6%)		9/150 (6%)
Vascular disorders
Hypertension	5/153 (3.3%)		10/150 (6.7%)

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 release and can embargo communications regarding trial results for a period that is less than or equal to 120 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.