Safety and Efficacy of a New Treatment as Adjunctive Therapy to Anti-vascular Endothelial Growth Factor (Anti-VEGF) Treatment in Patients With Age-Related Macular Degeneration (AMD)

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00511706
• Collaborator: (none)
• Enrollment: 243
• Locations: 9
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site: 27
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The study will evaluate the safety and efficacy of the intravitreal implant of dexamethasone with Anti-VEGF treatment vs. Anti-VEGF alone (with sham dexamethasone injection) in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

Condition or Disease	Intervention/Treatment	Phase
Choroidal Neovascularization; Age-Related Maculopathy	Drug: dexamethasone; Biological: ranibizumab; Other: sham	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 243 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dexamethasone and ranibizumab Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Drug: dexamethasone; Intravitreal injection of dexamethasone 700 µg at Day 1.; Other Names: Posurdex ; Biological: ranibizumab; Ranibizumab 500 µg at day -30 and Day 7-14.; Other Names: Lucentis®
Sham Comparator: sham and ranibizumab Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.	Biological: ranibizumab; Ranibizumab 500 µg at day -30 and Day 7-14.; Other Names: Lucentis® ; Other: sham; Sham needle-less injection administered in the study eye at Day 1.

Outcome Measures

Primary Outcome Measures

1. Injection Free Interval [Week 1 to Week 25]

   The injection free interval was defined as the number of days between receiving the second ranibizumab injection (day 7 to 14) to the investigator's determination of eligibility to receive a third ranibizumab injection in the study eye.

Secondary Outcome Measures

1. Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 [Baseline, Week 25]

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

2. Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye [Baseline, Week 25]

   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 25.

3. Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye [Screening (-Week 28), Week 25]

   Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the study eye after dilation at Screening and Week 25.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 50 years of age or older with subfoveal choroidal neovascularization (CNV) (classic and/or occult) secondary to AMD

• Visual Acuity between 20/40 and 20/400 in the study eye

Exclusion Criteria:

• Any intraocular surgery within 3 months

• Glaucoma

• Cataract

• High eye pressure

• Uncontrolled systemic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Boynton Beach	Florida	United States
2		Parramatta	New South Wales	Australia
3		Paris		France
4		Tel Aviv		Israel
5		Milano		Italy
6		Seoul		Korea, Republic of
7		Auckland		New Zealand
8		Coimbra		Portugal
9		Southampton	Hampshire	United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kuppermann BD, Goldstein M, Maturi RK, Pollack A, Singer M, Tufail A, Weinberger D, Li XY, Liu CC, Lou J, Whitcup SM; Ozurdex® ERIE Study Group. Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial. Ophthalmologica. 2015;234(1):40-54. doi: 10.1159/000381865. Epub 2015 Jun 18.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00511706
• Other Study ID Numbers: 206207-016
• First Posted: Aug 6, 2007
• Last Update Posted: Apr 25, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Choroidal Neovascularization; Macular Degeneration; Neovascularization, Pathologic; Dexamethasone; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Period Title: Overall Study
STARTED	123	120
COMPLETED	115	115
NOT COMPLETED	8	5

Baseline Characteristics

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab	Total
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.	Total of all reporting groups
Overall Participants	123	120	243
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	76.1 (8.83)	76.2 (8.50)	76.1 (8.65)
Sex: Female, Male (Count of Participants)
Female	76 61.8%	69 57.5%	145 59.7%
Male	47 38.2%	51 42.5%	98 40.3%

Outcome Measures

1. Primary Outcome

Title	Injection Free Interval
Description	The injection free interval was defined as the number of days between receiving the second ranibizumab injection (day 7 to 14) to the investigator's determination of eligibility to receive a third ranibizumab injection in the study eye.
Time Frame	Week 1 to Week 25

Outcome Measure Data

Analysis Population Description

Intent-to-treat population consisted of all randomized patients.

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Measure Participants	123	120
Median (Inter-Quartile Range) [Days]	34	29

2. Secondary Outcome

Title	Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame	Baseline, Week 25

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Measure Participants	122	120
Baseline	55.5 (15.27)	58.1 (12.64)
Change from baseline at week 25	2.0 (8.61)	2.4 (9.14)

3. Secondary Outcome

Title	Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye
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 25.
Time Frame	Baseline, Week 25

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Measure Participants	120	119
Baseline	260.28 (123.625)	272.45 (130.829)
Change from baseline at week 25 (n=105, 111)	-7.12 (77.898)	-13.00 (97.651)

4. Secondary Outcome

Title	Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye
Description	Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the study eye after dilation at Screening and Week 25.
Time Frame	Screening (-Week 28), Week 25

Outcome Measure Data

Analysis Population Description

Participants from the intent-to-treat population (all randomized participants) with data available at Screening and Week 25 for analyses.

Arm/Group Title	Dexamethasone and Ranibizumab	Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.	Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
Measure Participants	118	116
Screening	8.44 (6.863)	8.12 (6.359)
Change from Screening at Week 25 (n= 95,99)	-2.32 (4.927)	-1.73 (5.465)

Adverse Events

Adverse Event Reporting Description	Safety population was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events and was defined as all randomized participants who received study drug.
Arm/Group Title	Dexamethasone and Ranibizumab		Sham and Ranibizumab
Arm/Group Description	Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14.		Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14.
All Cause Mortality
	Dexamethasone and Ranibizumab		Sham and Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexamethasone and Ranibizumab		Sham and Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/121 (7.4%)		14/118 (11.9%)
Cardiac disorders
Myocardial infarction	1/121 (0.8%)		2/118 (1.7%)
Bradycardia	1/121 (0.8%)		0/118 (0%)
Cardiac failure chronic	0/121 (0%)		1/118 (0.8%)
Ischaemic cardiomyopathy	0/121 (0%)		1/118 (0.8%)
Mitral valve incompetence	0/121 (0%)		1/118 (0.8%)
Atrioventricular block complete	0/121 (0%)		1/118 (0.8%)
Atrial fibrillation	0/121 (0%)		2/118 (1.7%)
Gastrointestinal disorders
Small intestinal obstruction	1/121 (0.8%)		0/118 (0%)
Pancreatitis acute	1/121 (0.8%)		0/118 (0%)
Duodenal ulcer perforation	0/121 (0%)		1/118 (0.8%)
General disorders
Non-cardiac chest pain	0/121 (0%)		2/118 (1.7%)
Hernia	0/121 (0%)		1/118 (0.8%)
Hepatobiliary disorders
Cholelithiasis	0/121 (0%)		1/118 (0.8%)
Cholecystitis	1/121 (0.8%)		0/118 (0%)
Infections and infestations
Pneumonia	1/121 (0.8%)		3/118 (2.5%)
Gastroenteritis	1/121 (0.8%)		0/118 (0%)
Enterococcal infection	1/121 (0.8%)		0/118 (0%)
Appendicitis	0/121 (0%)		1/118 (0.8%)
Escherichia bacteraemia	0/121 (0%)		1/118 (0.8%)
Respiratory tract infection	0/121 (0%)		1/118 (0.8%)
Injury, poisoning and procedural complications
Therapeutic agent toxicity	1/121 (0.8%)		0/118 (0%)
Spinal compression fracture	1/121 (0.8%)		0/118 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/121 (0.8%)		0/118 (0%)
Failure to thrive	1/121 (0.8%)		0/118 (0%)
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/121 (0.8%)		0/118 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver	1/121 (0.8%)		0/118 (0%)
Basal cell carcinoma	0/121 (0%)		1/118 (0.8%)
Nervous system disorders
Stupor	1/121 (0.8%)		0/118 (0%)
Cerebrovascular accident	0/121 (0%)		1/118 (0.8%)
Renal and urinary disorders
Renal failure	1/121 (0.8%)		0/118 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/121 (0.8%)		2/118 (1.7%)
Other (Not Including Serious) Adverse Events
	Dexamethasone and Ranibizumab		Sham and Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/121 (71.1%)		59/118 (50%)
Eye disorders
Conjunctival haemorrhage	23/121 (19%)		12/118 (10.2%)
Intraocular pressure increased	16/121 (13.2%)		5/118 (4.2%)
Retinal haemorrhage	9/121 (7.4%)		7/118 (5.9%)
Visual acuity reduced	9/121 (7.4%)		5/118 (4.2%)
Macular degeneration	6/121 (5%)		5/118 (4.2%)
Vitreous floaters	6/121 (5%)		2/118 (1.7%)
Cataract subcapsular	6/121 (5%)		1/118 (0.8%)
Eye pain	5/121 (4.1%)		8/118 (6.8%)
Cataract	4/121 (3.3%)		7/118 (5.9%)
Vitreous detachment	2/121 (1.7%)		7/118 (5.9%)

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.