A Study of the Safety and Efficacy of a New Treatment for Macular Edema Resulting From Retinal Vein Occlusion
Study Details
Study Description
Brief Summary
This study will evaluate the safety and efficacy of an intravitreal implant of dexamethasone for the treatment of macular edema associated with retinal vein occlusion.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 700 µg Dexamethasone 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180. |
Drug: 700 µg Dexamethasone
700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.
Other Names:
|
Experimental: 350 µg Dexamethasone followed by 700 µg Dexamethasone 350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. |
Drug: 700 µg Dexamethasone
700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.
Other Names:
Drug: 350 µg Dexamethasone
350 µg Dexamethasone intravitreal implant administered on Day 0.
Other Names:
|
Sham Comparator: Sham Injection followed by 700 µg Dexamethasone Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. |
Drug: 700 µg Dexamethasone
700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.
Other Names:
Other: Sham Injection
Sham injection on Day 0.
|
Outcome Measures
Primary Outcome Measures
- Cumulative Response Rate of 15 or More Letter Improvement [Up to 180 Days]
The cumulative response rate of 15 or more letter improvement was based on the Kaplan-Meier estimate. A Kaplan-Meier analysis takes into account patients who dropped out from the study prior to achieving the 15 letter improvement. Values ranged from 0-1, with a higher number indicating a higher probability of response.
Secondary Outcome Measures
- Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye [Day 90, Day 180]
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye at each visit are presented.
- Change From Baseline in Retinal Thickness in the Study Eye [Baseline, Day 90, Day 180]
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement.
- Percentage of Patients With a Change From Baseline in BCVA by Category [Baseline, Day 90]
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.
- Percentage of Patients With a Change From Baseline in BCVA by Category [Baseline, Day 180]
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 years of age or older with macular edema resulting from retinal vein occlusion
-
Decrease in visual acuity in at least one eye as a result of macular edema (20/50 or worse)
-
Visual acuity in other eye no worse than 20/200
Exclusion Criteria:
-
Known anticipated need for ocular surgery within next 12 months
-
History of glaucoma or current high eye pressure requiring more than 1 medication
-
Diabetic retinopathy
-
Uncontrolled systemic disease
-
Known steroid-responder
-
Use of systemic steroids
-
Use of warfarin/heparin
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Los Angeles | California | United States | ||
2 | Sydney | Australia | |||
3 | Graz | Austria | |||
4 | Halifax | Nova Scotia | Canada | ||
5 | Brno | Czechia | |||
6 | Creteil | France | |||
7 | Karlsruhe | Germany | |||
8 | Rehovot | Israel | |||
9 | Tabacalera | Mexico | |||
10 | Makati | Philippines | |||
11 | Coimbra | Portugal | |||
12 | Arcadia | South Africa | |||
13 | Kaohsiung | Taiwan |
Sponsors and Collaborators
- Allergan
Investigators
- Study Director: Medical Director, Allergan
Study Documents (Full-Text)
None provided.More Information
Publications
- 206207-008
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Patients were randomly assigned during the double-blind period of the study to treatment with 700 µg dexamethasone, 350 µg dexamethasone, or sham injection on Day 0. Patients who qualified to continue in the open-label period of the study received 700 µg dexamethasone on Day 180. |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone Followed by 700 µg Dexamethasone | Sham Injection Followed by 700 µg Dexamethasone |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180. | 350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. | Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. |
Period Title: Double-Blind Period | |||
STARTED | 201 | 196 | 202 |
COMPLETED | 189 | 189 | 189 |
NOT COMPLETED | 12 | 7 | 13 |
Period Title: Double-Blind Period | |||
STARTED | 164 | 155 | 158 |
COMPLETED | 160 | 147 | 152 |
NOT COMPLETED | 4 | 8 | 6 |
Baseline Characteristics
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone Followed by 700 µg Dexamethasone | Sham Injection Followed by 700 µg Dexamethasone | Total |
---|---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180. | 350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. | Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. | Total of all reporting groups |
Overall Participants | 201 | 196 | 202 | 599 |
Age, Customized (participants) [Number] | ||||
<45 years |
9
4.5%
|
7
3.6%
|
9
4.5%
|
25
4.2%
|
45-65 years |
83
41.3%
|
84
42.9%
|
90
44.6%
|
257
42.9%
|
>65 years |
109
54.2%
|
105
53.6%
|
103
51%
|
317
52.9%
|
Sex: Female, Male (Count of Participants) | ||||
Female |
95
47.3%
|
92
46.9%
|
85
42.1%
|
272
45.4%
|
Male |
106
52.7%
|
104
53.1%
|
117
57.9%
|
327
54.6%
|
Outcome Measures
Title | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye |
---|---|
Description | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye at each visit are presented. |
Time Frame | Day 90, Day 180 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat: all randomized patients |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. |
Measure Participants | 201 | 196 | 202 |
Day 90 |
45
22.4%
|
41
20.9%
|
25
12.4%
|
Day 180 |
39
19.4%
|
32
16.3%
|
37
18.3%
|
Title | Change From Baseline in Retinal Thickness in the Study Eye |
---|---|
Description | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. |
Time Frame | Baseline, Day 90, Day 180 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat: all randomized patients |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. |
Measure Participants | 201 | 196 | 202 |
Baseline |
548.9
(185.45)
|
541.6
(183.68)
|
534.4
(187.38)
|
Change from Baseline at Day 90 |
-199.3
(194.54)
|
-144.1
(166.59)
|
-78.2
(150.05)
|
Change from Baseline at Day 180 |
-105.0
(197.83)
|
-91.4
(198.16)
|
-110.3
(175.59)
|
Title | Cumulative Response Rate of 15 or More Letter Improvement |
---|---|
Description | The cumulative response rate of 15 or more letter improvement was based on the Kaplan-Meier estimate. A Kaplan-Meier analysis takes into account patients who dropped out from the study prior to achieving the 15 letter improvement. Values ranged from 0-1, with a higher number indicating a higher probability of response. |
Time Frame | Up to 180 Days |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat: all randomized patients |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. |
Measure Participants | 201 | 196 | 202 |
Day 30 |
0.101
|
0.092
|
0.045
|
Day 60 |
0.258
|
0.204
|
0.100
|
Day 90 |
0.359
|
0.292
|
0.165
|
Day 180 |
0.397
|
0.349
|
0.225
|
Title | Percentage of Patients With a Change From Baseline in BCVA by Category |
---|---|
Description | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening. |
Time Frame | Baseline, Day 90 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat: all randomized patients |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. |
Measure Participants | 201 | 196 | 202 |
≥15 Letters Improvement |
22.4
|
20.9
|
12.4
|
≥5 and <15 Letters Improvement |
39.8
|
42.3
|
34.2
|
No Change (Between -5 to +5 Letters) |
27.4
|
23.5
|
34.7
|
≥5 and <15 Letters Worsening |
7.0
|
9.2
|
13.4
|
≥15 Letters Worsening |
3.5
|
4.1
|
5.4
|
Title | Percentage of Patients With a Change From Baseline in BCVA by Category |
---|---|
Description | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening. |
Time Frame | Baseline, Day 180 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat: all randomized patients |
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection |
---|---|---|---|
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. |
Measure Participants | 201 | 196 | 202 |
≥15 Letters Improvement |
19.4
|
16.3
|
18.3
|
≥5 and <15 Letters Improvement |
34.8
|
37.8
|
27.7
|
No Change (Between -5 to +5 Letters) |
29.4
|
25.5
|
30.2
|
≥5 and <15 Letters Worsening |
10.9
|
10.7
|
14.9
|
≥15 Letters Worsening |
5.5
|
9.7
|
8.9
|
Adverse Events
Time Frame | Adverse Events (AEs) and Serious Adverse Events (SAEs) are reported for the double-blind treatment period through Month 6. | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | The safety population included all randomized patients who received at least one dose of study medication and was used to assess AEs and SAEs. | |||||
Arm/Group Title | 700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection | |||
Arm/Group Description | 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180. | 350 µg Dexamethasone intravitreal implant administered on Day 0. | Sham injection on Day 0. | |||
All Cause Mortality |
||||||
700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 12/196 (6.1%) | 28/197 (14.2%) | 14/202 (6.9%) | |||
Cardiac disorders | ||||||
Angina pectoris | 2/196 (1%) | 0/197 (0%) | 0/202 (0%) | |||
Myocardial infarction | 1/196 (0.5%) | 4/197 (2%) | 0/202 (0%) | |||
Arrhythmia | 0/196 (0%) | 2/197 (1%) | 0/202 (0%) | |||
Cardiogenic shock | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Cardiac failure congestive | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Coronary artery stenosis | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Eye disorders | ||||||
Glaucoma | 0/196 (0%) | 1/197 (0.5%) | 1/202 (0.5%) | |||
Blindness | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Retinal vein occlusion | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Gastrointestinal disorders | ||||||
Pancreatitis | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
Small intestinal obstruction | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
General disorders | ||||||
Drowning | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Chest pain | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Infections and infestations | ||||||
Gastroenteritis | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Pneumonia | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Pneumonia viral | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Urinary tract infection | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Injury, poisoning and procedural complications | ||||||
Humerus fracture | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Investigations | ||||||
Intraocular pressure increased | 1/196 (0.5%) | 3/197 (1.5%) | 0/202 (0%) | |||
Blood pressure increased | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Osteoarthritis | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Spinal osteoarthritis | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Squamous cell carcinoma | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
Lipoma | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Lung adenocarcinoma | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Nervous system disorders | ||||||
Transient ischaemic attack | 1/196 (0.5%) | 1/197 (0.5%) | 1/202 (0.5%) | |||
Cerebrovascular accident | 1/196 (0.5%) | 1/197 (0.5%) | 0/202 (0%) | |||
Carotid artery stenosis | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
Syncope | 0/196 (0%) | 1/197 (0.5%) | 2/202 (1%) | |||
Convulsion | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Thrombotic stroke | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Psychiatric disorders | ||||||
Mental status changes | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
Renal and urinary disorders | ||||||
Renal colic | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Renal failure acute | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Reproductive system and breast disorders | ||||||
Benign prostatic hyperplasia | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Pulmonary embolism | 1/196 (0.5%) | 0/197 (0%) | 0/202 (0%) | |||
Respiratory failure | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Dyspnoea | 0/196 (0%) | 0/197 (0%) | 1/202 (0.5%) | |||
Vascular disorders | ||||||
Hypotension | 0/196 (0%) | 1/197 (0.5%) | 0/202 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
700 µg Dexamethasone | 350 µg Dexamethasone | Sham Injection | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 119/196 (60.7%) | 107/197 (54.3%) | 63/202 (31.2%) | |||
Eye disorders | ||||||
Conjunctival haemorrhage | 39/196 (19.9%) | 35/197 (17.8%) | 26/202 (12.9%) | |||
Eye pain | 13/196 (6.6%) | 8/197 (4.1%) | 7/202 (3.5%) | |||
Maculopathy | 11/196 (5.6%) | 7/197 (3.6%) | 17/202 (8.4%) | |||
Conjunctival hyperaemia | 10/196 (5.1%) | 11/197 (5.6%) | 7/202 (3.5%) | |||
Investigations | ||||||
Intraocular pressure increased | 46/196 (23.5%) | 46/197 (23.4%) | 6/202 (3%) |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Therapeutic Area Head |
---|---|
Organization | Allergan, Inc. |
Phone | (714)246-4500 |
clinicaltrials@allergan.com |
- 206207-008